- About
- Home
- Introduction
- Statistics
- Programs
- Dignet
- Gene
- GenePair
- BioSummarAI
- Help & Docs
- Documents
- Help
- FAQs
- Links
- Acknowledge
- Disclaimer
- Contact Us
Gene Information
Gene symbol: PIK3CA
Gene name: phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha
HGNC ID: 8975
Synonyms: PI3K
Related Genes
Related Sentences
| # | PMID | Sentence |
| 1 | 1309768 | Insulin stimulation of phosphatidylinositol 3-kinase activity maps to insulin receptor regions required for endogenous substrate phosphorylation. |
| 2 | 1309768 | We have studied the phosphatidylinositol 3-kinase (PtdIns 3-kinase) in insulin-stimulated Chinese hamster ovary (CHO) cells expressing normal (CHO/IR) and mutant human insulin receptors. |
| 3 | 1309768 | Insulin stimulation of CHO/IR cells results in an increase in PtdIns 3-kinase activity associated with anti-phosphotyrosine (alpha PY) immunoprecipitates, which has been previously shown to correlate with the in vivo production of PtdIns(3,4)P2, and PtdIns(3,4,5)P3 (Ruderman, N., Kapeller, R., White, M.F., and Cantley, L.C. (1990) Proc. |
| 4 | 1309768 | The PtdIns 3-kinase also associated with the insulin receptor in an insulin-stimulated manner, as approximately 50% of the total alpha PY-precipitable activity could be specifically immunoprecipitated with anti-insulin receptor antibody. |
| 5 | 1309768 | Mutant insulin receptors displayed variable ability to stimulate the PtdIns 3-kinase, but in all cases the presence of PtdIns 3-kinase in alpha PY immunoprecipitates correlated closely with the tyrosyl phosphorylation of the endogenous substrate pp185. |
| 6 | 1309768 | In CHO cells expressing a kinase-deficient mutant (IRA1018), there was no observable insulin stimulation of PtdIns 3-kinase activity in alpha PY immunoprecipitates and no tyrosyl phosphorylation of pp185. |
| 7 | 1309768 | Substitution of Tyr1146 in the insulin receptor regulatory region with phenylalanine partially impaired receptor autophosphorylation, pp185 phosphorylation, and insulin-stimulated increases in alpha PY-precipitable PtdIns 3-kinase activity. |
| 8 | 1309768 | Finally, a mutant receptor from which the C-terminal 43 amino acids had been deleted (IR delta CT) exhibited normal insulin-stimulated autophosphorylation, pp185 phosphorylation, and stimulation of the PtdIns 3-kinase activity in alpha PY immunoprecipitates. |
| 9 | 1309768 | These data suggest that the PtdIns 3-kinase is itself a substrate of the insulin receptor kinase or associates preferentially with a substrate. |
| 10 | 1309768 | A comparison of the biological activities of the mutant receptors with their activation of the PtdIns 3-kinase furthermore suggests that the PtdIns 3-kinase may be linked to insulin's ability to regulate DNA synthesis and cell growth. |
| 11 | 1309768 | Insulin stimulation of phosphatidylinositol 3-kinase activity maps to insulin receptor regions required for endogenous substrate phosphorylation. |
| 12 | 1309768 | We have studied the phosphatidylinositol 3-kinase (PtdIns 3-kinase) in insulin-stimulated Chinese hamster ovary (CHO) cells expressing normal (CHO/IR) and mutant human insulin receptors. |
| 13 | 1309768 | Insulin stimulation of CHO/IR cells results in an increase in PtdIns 3-kinase activity associated with anti-phosphotyrosine (alpha PY) immunoprecipitates, which has been previously shown to correlate with the in vivo production of PtdIns(3,4)P2, and PtdIns(3,4,5)P3 (Ruderman, N., Kapeller, R., White, M.F., and Cantley, L.C. (1990) Proc. |
| 14 | 1309768 | The PtdIns 3-kinase also associated with the insulin receptor in an insulin-stimulated manner, as approximately 50% of the total alpha PY-precipitable activity could be specifically immunoprecipitated with anti-insulin receptor antibody. |
| 15 | 1309768 | Mutant insulin receptors displayed variable ability to stimulate the PtdIns 3-kinase, but in all cases the presence of PtdIns 3-kinase in alpha PY immunoprecipitates correlated closely with the tyrosyl phosphorylation of the endogenous substrate pp185. |
| 16 | 1309768 | In CHO cells expressing a kinase-deficient mutant (IRA1018), there was no observable insulin stimulation of PtdIns 3-kinase activity in alpha PY immunoprecipitates and no tyrosyl phosphorylation of pp185. |
| 17 | 1309768 | Substitution of Tyr1146 in the insulin receptor regulatory region with phenylalanine partially impaired receptor autophosphorylation, pp185 phosphorylation, and insulin-stimulated increases in alpha PY-precipitable PtdIns 3-kinase activity. |
| 18 | 1309768 | Finally, a mutant receptor from which the C-terminal 43 amino acids had been deleted (IR delta CT) exhibited normal insulin-stimulated autophosphorylation, pp185 phosphorylation, and stimulation of the PtdIns 3-kinase activity in alpha PY immunoprecipitates. |
| 19 | 1309768 | These data suggest that the PtdIns 3-kinase is itself a substrate of the insulin receptor kinase or associates preferentially with a substrate. |
| 20 | 1309768 | A comparison of the biological activities of the mutant receptors with their activation of the PtdIns 3-kinase furthermore suggests that the PtdIns 3-kinase may be linked to insulin's ability to regulate DNA synthesis and cell growth. |
| 21 | 1310686 | Insulin increases phosphatidylinositol-3-kinase (PI-3-kinase) activity in Chinese hamster ovary cells transfected with human insulin receptor (Ruderman, N. |
| 22 | 1385396 | Insulin stimulation of phosphatidylinositol 3-kinase activity and association with insulin receptor substrate 1 in liver and muscle of the intact rat. |
| 23 | 1645354 | During insulin stimulation, the wild-type and mutant insulin receptor activated the phosphatidylinositol 3-kinase. |
| 24 | 1648180 | Structure of the insulin receptor substrate IRS-1 defines a unique signal transduction protein. |
| 25 | 1648180 | During insulin stimulation, the IRS-1 protein undergoes tyrosine phosphorylation and binds phosphatidylinositol 3-kinase, suggesting that IRS-1 acts as a multisite 'docking' protein to bind signal-transducing molecules containing Src-homology 2 and Src-homology-3 domains. |
| 26 | 1648180 | Thus IRS-1 may link the insulin receptor kinase and enzymes regulating cellular growth and metabolism. |
| 27 | 7485492 | Phosphorylated IRS-1 then interacts with the p85 alpha subunit of phosphatidylinositol 3-kinase (PI3K), Nck, growth factor receptor-bound protein 2 (GRB2), and Syp, thus branching insulin's signal for both mitogenic and metabolic responses. |
| 28 | 7485492 | IR and PI3K p85 alpha protein levels were significantly lower in KKAy mice than in control nondiabetic mice, whereas IRS-1 protein levels were not altered. |
| 29 | 7485492 | In contrast, the protein levels of GRB2, Nck, Syp, and GLUT-1 were dramatically elevated in KKAy fat, with less striking changes in liver. |
| 30 | 7485492 | Phosphorylated IRS-1 then interacts with the p85 alpha subunit of phosphatidylinositol 3-kinase (PI3K), Nck, growth factor receptor-bound protein 2 (GRB2), and Syp, thus branching insulin's signal for both mitogenic and metabolic responses. |
| 31 | 7485492 | IR and PI3K p85 alpha protein levels were significantly lower in KKAy mice than in control nondiabetic mice, whereas IRS-1 protein levels were not altered. |
| 32 | 7485492 | In contrast, the protein levels of GRB2, Nck, Syp, and GLUT-1 were dramatically elevated in KKAy fat, with less striking changes in liver. |
| 33 | 7505252 | In cell culture and in vitro, phosphorylated IRS-1 associates with the lipid-metabolizing enzyme phosphatidylinositol 3-kinase (PI 3-kinase), resulting in activation of this enzyme. |
| 34 | 7505252 | Thus, the insulin receptor, IRS-1 and PI-3 kinase represent three of the earliest steps in insulin action at the cellular level. |
| 35 | 7505252 | We have recently demonstrated that insulin is capable of stimulating PI 3-kinase activity in liver and muscle in vivo in animals and that IRS-1 phosphorylation may play a significant role in the association/activation with PI 3-kinase in vivo. |
| 36 | 7510688 | Two alternatively spliced forms of the human insulin-like growth factor I receptor have distinct biological activities and internalization kinetics. |
| 37 | 7510688 | Two alternatively spliced human insulin-like growth factor I (IGF I) receptor mRNA transcripts have been described that differ by three nucleotides (CAG) starting at position 2829. |
| 38 | 7510688 | The two receptors bound IGF I with similar affinity (Kd approximately 1.7 nM), but the CAG- form exhibited an approximately 2-fold increase in IGF I stimulation of receptor autophosphorylation, insulin receptor substrate-1 (IRS-1) tyrosine phosphorylation, thymidine incorporation, and IRS-1-associated phosphatidylinositol 3-kinase activity. |
| 39 | 7520127 | Regulation of insulin receptor, insulin receptor substrate-1 and phosphatidylinositol 3-kinase in 3T3-F442A adipocytes. |
| 40 | 7520127 | Insulin rapidly stimulates tyrosine kinase activity of its receptor resulting in phosphorylation of its cytosolic substrate insulin receptor substrate 1 (IRS-1), which in turn associates with and activates the enzyme phosphatidylinositol 3-kinase (PI 3-kinase). |
| 41 | 7520127 | The differentiation of 3T3-F442A cells was characterized by a 13-fold increase in insulin receptor protein, a 9-fold increase in IRS-1, and a 10- and 4.5-fold increase in their insulin-stimulated phosphorylation, respectively. |
| 42 | 7520127 | The expression of insulin receptor mRNA was unchanged, but the expression of IRS-1 mRNA was decreased by approximately 75% after dexamethasone. |
| 43 | 7520127 | Chronic treatment with 100 nM insulin induced a time- and dose-dependent decrease in insulin receptor and IRS-1 protein levels reaching a nadir of 34 +/- 5% (P < 0.005) and 39 +/- 5% (P < 0.01) of control levels after 24 h, respectively. |
| 44 | 7520127 | Chronic insulin treatment also produced a 30% decrease in PI 3-kinase protein levels and a approximately 50% decrease in the association/activation between IRS-1/PI 3-kinase. |
| 45 | 7520127 | The expression of insulin receptor and IRS-1 mRNA was unchanged during chronic insulin treatment. |
| 46 | 7520127 | Regulation of insulin receptor, insulin receptor substrate-1 and phosphatidylinositol 3-kinase in 3T3-F442A adipocytes. |
| 47 | 7520127 | Insulin rapidly stimulates tyrosine kinase activity of its receptor resulting in phosphorylation of its cytosolic substrate insulin receptor substrate 1 (IRS-1), which in turn associates with and activates the enzyme phosphatidylinositol 3-kinase (PI 3-kinase). |
| 48 | 7520127 | The differentiation of 3T3-F442A cells was characterized by a 13-fold increase in insulin receptor protein, a 9-fold increase in IRS-1, and a 10- and 4.5-fold increase in their insulin-stimulated phosphorylation, respectively. |
| 49 | 7520127 | The expression of insulin receptor mRNA was unchanged, but the expression of IRS-1 mRNA was decreased by approximately 75% after dexamethasone. |
| 50 | 7520127 | Chronic treatment with 100 nM insulin induced a time- and dose-dependent decrease in insulin receptor and IRS-1 protein levels reaching a nadir of 34 +/- 5% (P < 0.005) and 39 +/- 5% (P < 0.01) of control levels after 24 h, respectively. |
| 51 | 7520127 | Chronic insulin treatment also produced a 30% decrease in PI 3-kinase protein levels and a approximately 50% decrease in the association/activation between IRS-1/PI 3-kinase. |
| 52 | 7520127 | The expression of insulin receptor and IRS-1 mRNA was unchanged during chronic insulin treatment. |
| 53 | 7520528 | Second, we demonstrate a direct binding between purified SH2 and SH3 domains of Fyn and Lck Src family kinases. |
| 54 | 7520528 | Heterologous binding between SH2 and SH3 domains of closely related members of the Src family, namely, Fyn, Lck, and Src, was also observed. |
| 55 | 7520528 | In contrast, Grb2, Crk, Abl, p85 phosphatidylinositol 3-kinase, and GTPase-activating protein SH2 domains showed lower or no binding to Fyn or Lck SH3 domains. |
| 56 | 7520528 | SH3-SH2 binding was observed in the presence of proline-rich peptides or when a point mutation (W119K) was introduced in the putative ligand-binding pouch of the Fyn SH3 domain, although these treatments completely abolished the binding to p85 phosphatidylinositol 3-kinase and other SH3-specific polypeptides. |
| 57 | 7520528 | Second, we demonstrate a direct binding between purified SH2 and SH3 domains of Fyn and Lck Src family kinases. |
| 58 | 7520528 | Heterologous binding between SH2 and SH3 domains of closely related members of the Src family, namely, Fyn, Lck, and Src, was also observed. |
| 59 | 7520528 | In contrast, Grb2, Crk, Abl, p85 phosphatidylinositol 3-kinase, and GTPase-activating protein SH2 domains showed lower or no binding to Fyn or Lck SH3 domains. |
| 60 | 7520528 | SH3-SH2 binding was observed in the presence of proline-rich peptides or when a point mutation (W119K) was introduced in the putative ligand-binding pouch of the Fyn SH3 domain, although these treatments completely abolished the binding to p85 phosphatidylinositol 3-kinase and other SH3-specific polypeptides. |
| 61 | 7525562 | In addition, we demonstrate the association of the phosphorylated Leu323 mutant receptor with insulin receptor substrate-1 and with phosphatidylinositol 3-kinase. |
| 62 | 7525562 | These findings indicate that insulin binding is not required for phosphorylation of the Leu323 mutant receptor, that the phosphorylation of the Leu323 mutant receptor occurs by an intermolecular transphosphorylation mechanism, and, finally, that the Leu323 mutant receptor, once phosphorylated, can associate with insulin receptor substrate-1 and phosphatidylinositol 3-kinase. |
| 63 | 7525562 | In addition, we demonstrate the association of the phosphorylated Leu323 mutant receptor with insulin receptor substrate-1 and with phosphatidylinositol 3-kinase. |
| 64 | 7525562 | These findings indicate that insulin binding is not required for phosphorylation of the Leu323 mutant receptor, that the phosphorylation of the Leu323 mutant receptor occurs by an intermolecular transphosphorylation mechanism, and, finally, that the Leu323 mutant receptor, once phosphorylated, can associate with insulin receptor substrate-1 and phosphatidylinositol 3-kinase. |
| 65 | 7537758 | Insulin receptor phosphorylation, insulin receptor substrate-1 phosphorylation, and phosphatidylinositol 3-kinase activity are decreased in intact skeletal muscle strips from obese subjects. |
| 66 | 7537758 | To determine whether the impaired insulin-stimulated glucose uptake in obese individuals is associated with altered insulin receptor signaling, we measured both glucose uptake and early steps in the insulin action pathway in intact strips of human skeletal muscle. |
| 67 | 7537758 | In the lean subjects, tyrosine phosphorylation of the insulin receptor and insulin receptor substrate-1 (IRS-1), measured by immunoblotting with anti-phosphotyrosine antibodies, was significantly increased by insulin at all time points. |
| 68 | 7537758 | In the skeletal muscle from the obese subjects, insulin was less effective in stimulating tyrosine phosphorylation (maximum receptor and IRS-1 phosphorylation decreased by 35 and 38%, respectively). |
| 69 | 7537758 | Insulin stimulation of IRS-1 immunoprecipitable phosphatidylinositol 3-kinase (PI 3-kinase) activity also was markedly lower in obese subjects compared with controls (10- vs 35-fold above basal, respectively). |
| 70 | 7537758 | In addition, the obese subjects had a lower abundance of the insulin receptor, IRS-1, and the p85 subunit of PI 3-kinase (55, 54, and 64% of nonobese, respectively). |
| 71 | 7537758 | We conclude that impaired insulin-stimulated glucose uptake in skeletal muscle from severely obese subjects is accompanied by a deficiency in insulin receptor signaling, which may contribute to decreased insulin action. |
| 72 | 7537758 | Insulin receptor phosphorylation, insulin receptor substrate-1 phosphorylation, and phosphatidylinositol 3-kinase activity are decreased in intact skeletal muscle strips from obese subjects. |
| 73 | 7537758 | To determine whether the impaired insulin-stimulated glucose uptake in obese individuals is associated with altered insulin receptor signaling, we measured both glucose uptake and early steps in the insulin action pathway in intact strips of human skeletal muscle. |
| 74 | 7537758 | In the lean subjects, tyrosine phosphorylation of the insulin receptor and insulin receptor substrate-1 (IRS-1), measured by immunoblotting with anti-phosphotyrosine antibodies, was significantly increased by insulin at all time points. |
| 75 | 7537758 | In the skeletal muscle from the obese subjects, insulin was less effective in stimulating tyrosine phosphorylation (maximum receptor and IRS-1 phosphorylation decreased by 35 and 38%, respectively). |
| 76 | 7537758 | Insulin stimulation of IRS-1 immunoprecipitable phosphatidylinositol 3-kinase (PI 3-kinase) activity also was markedly lower in obese subjects compared with controls (10- vs 35-fold above basal, respectively). |
| 77 | 7537758 | In addition, the obese subjects had a lower abundance of the insulin receptor, IRS-1, and the p85 subunit of PI 3-kinase (55, 54, and 64% of nonobese, respectively). |
| 78 | 7537758 | We conclude that impaired insulin-stimulated glucose uptake in skeletal muscle from severely obese subjects is accompanied by a deficiency in insulin receptor signaling, which may contribute to decreased insulin action. |
| 79 | 7540574 | Glucose-induced insulin receptor tyrosine phosphorylation in insulin-secreting beta-cells. |
| 80 | 7540574 | In the beta TC3 insulin-secreting beta-cell line, glucose rapidly induces the tyrosine phosphorylation of the 97-kDa insulin receptor beta-subunit. |
| 81 | 7540574 | In addition, functional insulin-like growth factor I (IGF-I) receptors are also expressed by these beta-cells, as indicated by IGF-I-induced receptor tyrosine phosphorylation (ED50 = 5 x 10(-9) mol/l) and also by detection of hybrid insulin/IGF-I receptor autophosphorylation at 10(-7) mol/l IGF-I. |
| 82 | 7540574 | Both glucose and insulin stimulate the tyrosine phosphorylation of the insulin receptor substrate (IRS) IRS-1 and increase by two- to fivefold the rapid association of IRS-1 with the 85-kDa alpha-subunit of the phosphatidylinositol-3-kinase, as determined by co-immunoprecipitation assays. |
| 83 | 7542745 | Phosphatidylinositol 3-kinase (PI-3 kinase) is implicated in the regulation of diverse cellular processes, including insulin-stimulated glucose transport. |
| 84 | 7542745 | Here, we describe p55PIK, a new regulatory subunit that was isolated by screening expression libraries with tyrosine-phosphorylated insulin receptor substrate 1 (IRS-1). p55PIK is composed of a unique 30-residue NH2 terminus followed by a proline-rich motif and two Src homology 2 (SH2) domains with significant sequence identify to those in p85. p55PIK mRNA is expressed early during development, remains abundant in adult mouse brain and testis tissue, and is detectable in adult adipocytes and heart and kidney tissues. p55PIK forms a stable complex with p110, and it associates with IRS-1 during insulin stimulation. |
| 85 | 7544807 | Dexamethasone enhances insulin-like growth factor-I effects on skeletal muscle cell proliferation. |
| 86 | 7544807 | IGF-I stimulation of cell proliferation and c-Fos expression in skeletal muscle cells is markedly enhanced by dexamethasone. |
| 87 | 7544807 | The effect of dexamethasone is not mediated by changes in IGF-binding proteins, as evidenced by similar effects of dexamethasone on the actions of insulin, PDGF-BB, and the IGF-I analogue long R3IGF-I. |
| 88 | 7544807 | In dexamethasone-treated cells, the levels of IGF-I receptor tyrosine phosphorylation and receptor-associated phosphatidylinositol 3-kinase activity were increased. |
| 89 | 7544807 | In contrast, dexamethasone decreased both tyrosine phosphorylation and expression of insulin receptor substrate 1 (IRS-1) and IRS-1-associated phosphatidylinositol 3-kinase activity. |
| 90 | 7544807 | Potentiation of IGF-I action correlates with increased IGF-I receptor-associated phosphatidylinositol 3-kinase activity and tyrosine phosphorylation of Shc, but appears to be independent of activation of the IRS-1/phosphatidylinositol 3-kinase signaling pathway. |
| 91 | 7544807 | Dexamethasone enhances insulin-like growth factor-I effects on skeletal muscle cell proliferation. |
| 92 | 7544807 | IGF-I stimulation of cell proliferation and c-Fos expression in skeletal muscle cells is markedly enhanced by dexamethasone. |
| 93 | 7544807 | The effect of dexamethasone is not mediated by changes in IGF-binding proteins, as evidenced by similar effects of dexamethasone on the actions of insulin, PDGF-BB, and the IGF-I analogue long R3IGF-I. |
| 94 | 7544807 | In dexamethasone-treated cells, the levels of IGF-I receptor tyrosine phosphorylation and receptor-associated phosphatidylinositol 3-kinase activity were increased. |
| 95 | 7544807 | In contrast, dexamethasone decreased both tyrosine phosphorylation and expression of insulin receptor substrate 1 (IRS-1) and IRS-1-associated phosphatidylinositol 3-kinase activity. |
| 96 | 7544807 | Potentiation of IGF-I action correlates with increased IGF-I receptor-associated phosphatidylinositol 3-kinase activity and tyrosine phosphorylation of Shc, but appears to be independent of activation of the IRS-1/phosphatidylinositol 3-kinase signaling pathway. |
| 97 | 7544807 | Dexamethasone enhances insulin-like growth factor-I effects on skeletal muscle cell proliferation. |
| 98 | 7544807 | IGF-I stimulation of cell proliferation and c-Fos expression in skeletal muscle cells is markedly enhanced by dexamethasone. |
| 99 | 7544807 | The effect of dexamethasone is not mediated by changes in IGF-binding proteins, as evidenced by similar effects of dexamethasone on the actions of insulin, PDGF-BB, and the IGF-I analogue long R3IGF-I. |
| 100 | 7544807 | In dexamethasone-treated cells, the levels of IGF-I receptor tyrosine phosphorylation and receptor-associated phosphatidylinositol 3-kinase activity were increased. |
| 101 | 7544807 | In contrast, dexamethasone decreased both tyrosine phosphorylation and expression of insulin receptor substrate 1 (IRS-1) and IRS-1-associated phosphatidylinositol 3-kinase activity. |
| 102 | 7544807 | Potentiation of IGF-I action correlates with increased IGF-I receptor-associated phosphatidylinositol 3-kinase activity and tyrosine phosphorylation of Shc, but appears to be independent of activation of the IRS-1/phosphatidylinositol 3-kinase signaling pathway. |
| 103 | 7626133 | Tyrosine-phosphorylation of IRS-1 causes it to associate with the src-homology-2 (SH2) domains of at least four other proteins: phosphatidylinositol 3'-kinase (PI3K), growth factor receptor-bound protein-2 (GRB2), Nck, and Syp. |
| 104 | 7626133 | In liver tissue of diabetic rats, the levels of Nck and Syp were significantly decreased to 71 +/- 6% and 61 +/- 4% control, respectively, while in fat tissue only the Syp levels were significantly reduced to 72 +/- 9% control. |
| 105 | 7680644 | Here we develop a new approach to analyzing protein-protein interfaces termed photoaffinity scanning, and apply the method to map regions of the phosphatidylinositol 3-kinase p85 SH2 domain that participate in phospho-protein binding. |
| 106 | 7691886 | Regulation of phosphatidylinositol 3-kinase activity in liver and muscle of animal models of insulin-resistant and insulin-deficient diabetes mellitus. |
| 107 | 7691886 | Insulin stimulates tyrosine phosphorylation of insulin receptor substrate 1 (IRS-1), which in turn binds to and activates phosphatidylinositol 3-kinase (PI 3-kinase). |
| 108 | 7691886 | After in vivo insulin stimulation, there was a 60-80% decrease in IRS-1 phosphorylation in liver and muscle of the ob/ob mouse. |
| 109 | 7691886 | There was no insulin stimulation of PI 3-kinase (85 kD subunit) association with IRS-1, and IRS-1-associated PI 3-kinase activity was reduced 90%. |
| 110 | 7691886 | By contrast, in the streptozotocin diabetic rat, IRS-1 phosphorylation increased 50% in muscle, IRS-1-associated PI 3-kinase activity was increased two- to threefold in liver and muscle, and there was a 50% increase in the p85 associated with IRS-1 after insulin stimulation in muscle. |
| 111 | 7691886 | In conclusion, (a) IRS-1-associated PI 3-kinase activity is differentially regulated in hyperinsulinemic and hypoinsulinemic diabetic states; (b) PI 3-kinase activation closely correlates with IRS-1 phosphorylation; and (c) reduced PI 3-kinase activity may play a role in the pathophysiology of insulin resistant diabetic states, such as that seen in the ob/ob mouse. |
| 112 | 7691886 | Regulation of phosphatidylinositol 3-kinase activity in liver and muscle of animal models of insulin-resistant and insulin-deficient diabetes mellitus. |
| 113 | 7691886 | Insulin stimulates tyrosine phosphorylation of insulin receptor substrate 1 (IRS-1), which in turn binds to and activates phosphatidylinositol 3-kinase (PI 3-kinase). |
| 114 | 7691886 | After in vivo insulin stimulation, there was a 60-80% decrease in IRS-1 phosphorylation in liver and muscle of the ob/ob mouse. |
| 115 | 7691886 | There was no insulin stimulation of PI 3-kinase (85 kD subunit) association with IRS-1, and IRS-1-associated PI 3-kinase activity was reduced 90%. |
| 116 | 7691886 | By contrast, in the streptozotocin diabetic rat, IRS-1 phosphorylation increased 50% in muscle, IRS-1-associated PI 3-kinase activity was increased two- to threefold in liver and muscle, and there was a 50% increase in the p85 associated with IRS-1 after insulin stimulation in muscle. |
| 117 | 7691886 | In conclusion, (a) IRS-1-associated PI 3-kinase activity is differentially regulated in hyperinsulinemic and hypoinsulinemic diabetic states; (b) PI 3-kinase activation closely correlates with IRS-1 phosphorylation; and (c) reduced PI 3-kinase activity may play a role in the pathophysiology of insulin resistant diabetic states, such as that seen in the ob/ob mouse. |
| 118 | 7691892 | Modulation of insulin receptor, insulin receptor substrate-1, and phosphatidylinositol 3-kinase in liver and muscle of dexamethasone-treated rats. |
| 119 | 7691892 | Insulin rapidly stimulates tyrosine kinase activity of its receptor resulting in phosphorylation of its cytosolic substrate, insulin receptor substrate-1 (IRS-1), which in turn associates with phosphatidylinositol 3-kinase (PI 3-kinase), thus activating the enzyme. |
| 120 | 7691892 | In the present study we have examined the levels and phosphorylation state of the insulin receptor and IRS-1, as well as the association/activation between IRS-1 and PI 3-kinase in the liver and muscle of rats treated with dexamethasone. |
| 121 | 7691892 | By contrast, IRS-1 phosphorylation was decreased by 31.3 +/- 10.9% (P < 0.05), and insulin stimulated PI 3-kinase activity in anti-IRS-1 immunoprecipitates was decreased by 79.5 +/- 11.2% (P < 0.02). |
| 122 | 7691892 | IRS-1 phosphorylation showed no significant change in muscle, but insulin-stimulated IRS-1 associated PI 3-kinase was decreased by 41%. |
| 123 | 7691892 | Modulation of insulin receptor, insulin receptor substrate-1, and phosphatidylinositol 3-kinase in liver and muscle of dexamethasone-treated rats. |
| 124 | 7691892 | Insulin rapidly stimulates tyrosine kinase activity of its receptor resulting in phosphorylation of its cytosolic substrate, insulin receptor substrate-1 (IRS-1), which in turn associates with phosphatidylinositol 3-kinase (PI 3-kinase), thus activating the enzyme. |
| 125 | 7691892 | In the present study we have examined the levels and phosphorylation state of the insulin receptor and IRS-1, as well as the association/activation between IRS-1 and PI 3-kinase in the liver and muscle of rats treated with dexamethasone. |
| 126 | 7691892 | By contrast, IRS-1 phosphorylation was decreased by 31.3 +/- 10.9% (P < 0.05), and insulin stimulated PI 3-kinase activity in anti-IRS-1 immunoprecipitates was decreased by 79.5 +/- 11.2% (P < 0.02). |
| 127 | 7691892 | IRS-1 phosphorylation showed no significant change in muscle, but insulin-stimulated IRS-1 associated PI 3-kinase was decreased by 41%. |
| 128 | 7762655 | Insulin stimulates signaling reactions that include insulin receptor autophosphorylation and tyrosine kinase activation, insulin receptor substrate-1 (IRS-1) tyrosine phosphorylation, and phosphatidylinositol 3-kinase (PI 3-kinase) activation. |
| 129 | 7762655 | Insulin increased tyrosine phosphorylation of the insulin receptor and IRS-1, whereas contraction alone had no effect. |
| 130 | 7762655 | Contraction before insulin injection decreased the insulin effect on receptor and IRS-1 phosphorylation by 20-25%. |
| 131 | 7762655 | Contraction alone had little effect on PI 3-kinase activity, but contraction markedly blunted the insulin-stimulated activation of IRS-1 and insulin receptor-immunoprecipitable PI 3-kinase. |
| 132 | 7777579 | Phosphatidylinositol 3-kinase signals activation of p70 S6 kinase in situ through site-specific p70 phosphorylation. |
| 133 | 7777579 | The p70 S6 kinase is activated by insulin and mitogens through multisite phosphorylation of the enzyme. |
| 134 | 7895667 | Insulin and dexamethasone regulate insulin receptors, insulin receptor substrate-1, and phosphatidylinositol 3-kinase in Fao hepatoma cells. |
| 135 | 7895667 | Insulin rapidly stimulates tyrosine kinase activity of its receptor, resulting in phosphorylation of the cytosolic substrate, insulin receptor substrate-1 (IRS-1), which, in turn, associates with phosphatidylinositol 3-kinase (PI 3-kinase), thus activating the enzyme. |
| 136 | 7895667 | Prolonged insulin treatment induced a time- and dose-dependent decrease in insulin receptor and IRS-1 protein levels, reaching nadirs of 40 +/- 4% (P < 0.01) and 15 +/- 6% (P < 0.005) of control levels, respectively, after 24 h with 100 nM insulin. |
| 137 | 7895667 | There was also a decrease in the phosphorylation of insulin receptors and IRS-1, a marked decrease in the association between IRS-1 and PI 3-kinase, and an 82% decrease in insulin-stimulated PI 3-kinase activity without a significant change in PI 3-kinase protein levels. |
| 138 | 7895667 | When cells were exposed to both insulin and dexamethasone, the effect of insulin to reduce insulin receptor and IRS-1 levels and insulin-stimulated IRS-1 phosphorylation dominated. |
| 139 | 7895667 | These data suggest that regulation of the insulin receptor, IRS-1, and PI 3-kinase contributes significantly to the insulin resistance induced by chronic hyperinsulinemia, but that glucocorticoid-induced insulin resistance is located beyond these early steps in insulin action. |
| 140 | 7895667 | Insulin and dexamethasone regulate insulin receptors, insulin receptor substrate-1, and phosphatidylinositol 3-kinase in Fao hepatoma cells. |
| 141 | 7895667 | Insulin rapidly stimulates tyrosine kinase activity of its receptor, resulting in phosphorylation of the cytosolic substrate, insulin receptor substrate-1 (IRS-1), which, in turn, associates with phosphatidylinositol 3-kinase (PI 3-kinase), thus activating the enzyme. |
| 142 | 7895667 | Prolonged insulin treatment induced a time- and dose-dependent decrease in insulin receptor and IRS-1 protein levels, reaching nadirs of 40 +/- 4% (P < 0.01) and 15 +/- 6% (P < 0.005) of control levels, respectively, after 24 h with 100 nM insulin. |
| 143 | 7895667 | There was also a decrease in the phosphorylation of insulin receptors and IRS-1, a marked decrease in the association between IRS-1 and PI 3-kinase, and an 82% decrease in insulin-stimulated PI 3-kinase activity without a significant change in PI 3-kinase protein levels. |
| 144 | 7895667 | When cells were exposed to both insulin and dexamethasone, the effect of insulin to reduce insulin receptor and IRS-1 levels and insulin-stimulated IRS-1 phosphorylation dominated. |
| 145 | 7895667 | These data suggest that regulation of the insulin receptor, IRS-1, and PI 3-kinase contributes significantly to the insulin resistance induced by chronic hyperinsulinemia, but that glucocorticoid-induced insulin resistance is located beyond these early steps in insulin action. |
| 146 | 7895862 | After phosphorylation by the insulin receptor, IRS-1 binds to the specific molecules which possess SH2 (src homology 2) domain such as 85 kDa subunit of phosphatidylinositol 3 kinase and may mediate insulin signals. |
| 147 | 7895862 | The regulation of IRS-1 has been analyzed in animal models of insulin resistance, and its mechanism has been studied in culture cells. |
| 148 | 7895862 | In animal models of insulin resistance, phosphorylation of IRS-1 was mainly regulated by the insulin receptor tyrosine kinase both in liver and muscle. |
| 149 | 7895862 | In cultured cell such as 3T3-L1 or 3T3-F442A adipocytes, IRS-1 was negatively regulated both by insulin and dexamethasone by different mechanisms. |
| 150 | 7895862 | Insulin regulates the IRS-1 expression at protein level mainly by decreasing the half life of IRS-1 protein, and dexamethasone regulates it at mRNA level mainly by decreasing the half life of IRS-1 mRNA. |
| 151 | 7926303 | The expressed receptor was able to mediate an insulin-stimulated increase in both anti-phosphotyrosine-precipitable and anti-insulin receptor substrate 1-precipitable phosphatidylinositol 3-kinase activity. |
| 152 | 7965046 | Insulin receptor substrate 1 (IRS-1) is the primary cytosolic substrate of the insulin and insulin-like growth factor-I (IGF-I) receptors. |
| 153 | 7965046 | Using biochemical and immunocytochemical techniques, we have mapped the distribution of IRS-1 in the CNS of the adult rat and compared it with that of insulin and IGF-I receptors and phosphatidylinositol 3-kinase (PI-3 kinase), a signaling molecule functionally related to IRS-1. |
| 154 | 7965046 | Immunoprecipitation and Western blotting experiments demonstrate the presence of substantial amounts of IRS-1, insulin receptor, and PI-3 kinase in the brain. |
| 155 | 7965046 | In these areas most of the neurons immunoreactive for IRS-1 are also stained by either anti-insulin receptor or anti-IGF-I receptor antibodies as well as PI-3 kinase antiserum. |
| 156 | 7965046 | IRS-1 immunostaining was very weak or totally absent in neurons of the olfactory bulb, the supraoptic and paraventricular nuclei, the mesencephalic trigeminal nucleus, and the granule cell layer of the cerebellum, despite the fact that these areas were immunolabeled with antibodies against insulin or IGF-I receptors and/or PI-3 kinase. |
| 157 | 7965046 | These results show that neurons in the adult rat CNS are endowed with some of the components of the early signaling pathway for growth factors of the insulin/IGF-I family, although IRS-1 has a distribution distinct from that of the two receptors. |
| 158 | 8007986 | Phosphatidylinositol 3-kinase activation is required for insulin stimulation of pp70 S6 kinase, DNA synthesis, and glucose transporter translocation. |
| 159 | 8007986 | Phosphatidylinositol 3-kinase (PI 3-kinase) is stimulated by insulin and a variety of growth factors, but its exact role in signal transduction remains unclear. |
| 160 | 8007986 | Inhibition of PI 3-kinase also effectively blocked insulin- and serum-stimulated DNA synthesis and insulin-stimulated glucose uptake by inhibiting translocation of GLUT 4 glucose transporters to the plasma membrane. |
| 161 | 8007986 | Phosphatidylinositol 3-kinase activation is required for insulin stimulation of pp70 S6 kinase, DNA synthesis, and glucose transporter translocation. |
| 162 | 8007986 | Phosphatidylinositol 3-kinase (PI 3-kinase) is stimulated by insulin and a variety of growth factors, but its exact role in signal transduction remains unclear. |
| 163 | 8007986 | Inhibition of PI 3-kinase also effectively blocked insulin- and serum-stimulated DNA synthesis and insulin-stimulated glucose uptake by inhibiting translocation of GLUT 4 glucose transporters to the plasma membrane. |
| 164 | 8058065 | The level of insulin receptor tyrosine kinase activity modulates the activities of phosphatidylinositol 3-kinase, microtubule-associated protein, and S6 kinases. |
| 165 | 8058065 | The role of insulin receptor tyrosine kinase activity in stimulation of intracellular enzymes linked to insulin action [phosphatidylinositol 3-kinase (PtdIns 3-kinase), microtubule-associated protein (MAP) kinase, and S6 kinases] was studied in Chinese hamster ovary cells which overexpress wild type human insulin receptors, receptors with reduced kinase activity due to substitution of Phe for Tyr1146 (single-Phe), Tyr1150,1151 (double-Phe), and Tyr1146,1150,1151 (triple-Phe), or kinase-inactive receptors with a substitution of Ala for Lys1018 in the ATP binding site (A1018). |
| 166 | 8058065 | Overexpression of the wild type insulin receptor increased both maximal insulin receptor substrate-1-associated and total insulin-stimulated PtdIns 3-kinase activity, as well as S6 and MAP kinase activities 2.0- to 3.6-fold. |
| 167 | 8058065 | Expression of the single- and double-Phe mutant receptors also enhanced maximal PtdIns 3-kinase activity, but had no effect on insulin sensitivity, whereas expression of either the triple-Phe or kinase-inactive receptors did not enhance insulin stimulation or increase insulin sensitivity as compared to the control cells. |
| 168 | 8058065 | When comparing the mutant and wild type receptors, differences in insulin sensitivity were least for insulin-stimulated MAP kinase and greatest for S6 kinase; with the latter there was greater than a 1000-fold difference in insulin sensitivity when cells that overexpress wild type vs. kinase-inactive insulin receptors were compared. |
| 169 | 8058065 | The level of insulin receptor tyrosine kinase activity modulates the activities of phosphatidylinositol 3-kinase, microtubule-associated protein, and S6 kinases. |
| 170 | 8058065 | The role of insulin receptor tyrosine kinase activity in stimulation of intracellular enzymes linked to insulin action [phosphatidylinositol 3-kinase (PtdIns 3-kinase), microtubule-associated protein (MAP) kinase, and S6 kinases] was studied in Chinese hamster ovary cells which overexpress wild type human insulin receptors, receptors with reduced kinase activity due to substitution of Phe for Tyr1146 (single-Phe), Tyr1150,1151 (double-Phe), and Tyr1146,1150,1151 (triple-Phe), or kinase-inactive receptors with a substitution of Ala for Lys1018 in the ATP binding site (A1018). |
| 171 | 8058065 | Overexpression of the wild type insulin receptor increased both maximal insulin receptor substrate-1-associated and total insulin-stimulated PtdIns 3-kinase activity, as well as S6 and MAP kinase activities 2.0- to 3.6-fold. |
| 172 | 8058065 | Expression of the single- and double-Phe mutant receptors also enhanced maximal PtdIns 3-kinase activity, but had no effect on insulin sensitivity, whereas expression of either the triple-Phe or kinase-inactive receptors did not enhance insulin stimulation or increase insulin sensitivity as compared to the control cells. |
| 173 | 8058065 | When comparing the mutant and wild type receptors, differences in insulin sensitivity were least for insulin-stimulated MAP kinase and greatest for S6 kinase; with the latter there was greater than a 1000-fold difference in insulin sensitivity when cells that overexpress wild type vs. kinase-inactive insulin receptors were compared. |
| 174 | 8088704 | A model of insulin resistance has recently been described in which the insulin receptor is expressed in Chinese hamster ovary cells along with the phospholipid- and calcium-activated serine/threonine kinase called protein kinase C. |
| 175 | 8088704 | In this model system, activation of protein kinase C is shown to interfere with insulin receptor signalling by inhibiting tyrosine phosphorylation of IRS-1 and its subsequent binding by phosphatidylinositol 3-kinase. |
| 176 | 8382612 | An example of such phosphoprotein-effector coupling is provided by the association of phosphatidylinositol 3-kinase (PI 3-kinase) with specific phosphorylation sites within the PDGF receptor, the c-Src/polyoma virus middle T antigen complex and the insulin receptor substrate IRS-1. |
| 177 | 8382612 | To investigate how phosphoprotein binding to the p85 SH2 domain stimulates p110 catalytic activation, we have examined the differential effects of phosphotyrosine and PDGF receptor-, IRS-1- and c-Src-derived phosphopeptides on the conformation of an isolated SH2 domain of PI 3-kinase. |
| 178 | 8384875 | Phosphatidylinositol 3-kinase p85 SH2 domain specificity defined by direct phosphopeptide/SH2 domain binding. |
| 179 | 8384875 | Eleven synthetic 11-12-amino acid phosphopeptides containing YMXM or YVXM recognition motifs bound to a PI 3-kinase p85 SH2 domain with highest affinities, including sequences surrounding phosphorylated tyrosines of the PDGF, CSF-1/c-Fms, and kit-encoded receptors, IRS-1, and polyoma middle T antigens; matched, unphosphorylated sequences did not bind. |
| 180 | 8384875 | A scrambled YMXM phosphopeptide or sequences corresponding to the GAP or PLC-gamma SH2 domain binding motifs of the PDGF, FGF, and EGF receptors bound to the p85 SH2 domain with 30-100-fold reduced affinity, indicating that this affinity range confers specificity. |
| 181 | 8386184 | Defect in skeletal muscle phosphatidylinositol-3-kinase in obese insulin-resistant mice. |
| 182 | 8386184 | Activation of phosphatidylinositol-3-kinase (PI3K) is one of the earliest postreceptor events in the insulin signaling pathway. |
| 183 | 8386184 | Incubation of soleus muscles from lean mice with 50 nM insulin caused a 3-10-fold increase in antiphosphotyrosine-immunoprecipitable PI3K (antiPTyr-PI3K) activity within 2 min in muscle homogenates as well as both the cytosolic and membrane fractions. |
| 184 | 8386184 | Insulin did not affect total PI3K activity. |
| 185 | 8386184 | Starvation of obese mice for 48 h, which is known to reverse insulin resistance, normalized the insulin response of both PI3K and the receptor tyrosine kinase. |
| 186 | 8386184 | Defect in skeletal muscle phosphatidylinositol-3-kinase in obese insulin-resistant mice. |
| 187 | 8386184 | Activation of phosphatidylinositol-3-kinase (PI3K) is one of the earliest postreceptor events in the insulin signaling pathway. |
| 188 | 8386184 | Incubation of soleus muscles from lean mice with 50 nM insulin caused a 3-10-fold increase in antiphosphotyrosine-immunoprecipitable PI3K (antiPTyr-PI3K) activity within 2 min in muscle homogenates as well as both the cytosolic and membrane fractions. |
| 189 | 8386184 | Insulin did not affect total PI3K activity. |
| 190 | 8386184 | Starvation of obese mice for 48 h, which is known to reverse insulin resistance, normalized the insulin response of both PI3K and the receptor tyrosine kinase. |
| 191 | 8386184 | Defect in skeletal muscle phosphatidylinositol-3-kinase in obese insulin-resistant mice. |
| 192 | 8386184 | Activation of phosphatidylinositol-3-kinase (PI3K) is one of the earliest postreceptor events in the insulin signaling pathway. |
| 193 | 8386184 | Incubation of soleus muscles from lean mice with 50 nM insulin caused a 3-10-fold increase in antiphosphotyrosine-immunoprecipitable PI3K (antiPTyr-PI3K) activity within 2 min in muscle homogenates as well as both the cytosolic and membrane fractions. |
| 194 | 8386184 | Insulin did not affect total PI3K activity. |
| 195 | 8386184 | Starvation of obese mice for 48 h, which is known to reverse insulin resistance, normalized the insulin response of both PI3K and the receptor tyrosine kinase. |
| 196 | 8386184 | Defect in skeletal muscle phosphatidylinositol-3-kinase in obese insulin-resistant mice. |
| 197 | 8386184 | Activation of phosphatidylinositol-3-kinase (PI3K) is one of the earliest postreceptor events in the insulin signaling pathway. |
| 198 | 8386184 | Incubation of soleus muscles from lean mice with 50 nM insulin caused a 3-10-fold increase in antiphosphotyrosine-immunoprecipitable PI3K (antiPTyr-PI3K) activity within 2 min in muscle homogenates as well as both the cytosolic and membrane fractions. |
| 199 | 8386184 | Insulin did not affect total PI3K activity. |
| 200 | 8386184 | Starvation of obese mice for 48 h, which is known to reverse insulin resistance, normalized the insulin response of both PI3K and the receptor tyrosine kinase. |
| 201 | 8386184 | Defect in skeletal muscle phosphatidylinositol-3-kinase in obese insulin-resistant mice. |
| 202 | 8386184 | Activation of phosphatidylinositol-3-kinase (PI3K) is one of the earliest postreceptor events in the insulin signaling pathway. |
| 203 | 8386184 | Incubation of soleus muscles from lean mice with 50 nM insulin caused a 3-10-fold increase in antiphosphotyrosine-immunoprecipitable PI3K (antiPTyr-PI3K) activity within 2 min in muscle homogenates as well as both the cytosolic and membrane fractions. |
| 204 | 8386184 | Insulin did not affect total PI3K activity. |
| 205 | 8386184 | Starvation of obese mice for 48 h, which is known to reverse insulin resistance, normalized the insulin response of both PI3K and the receptor tyrosine kinase. |
| 206 | 8393870 | In CHO-Y960F cells, tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1), the activation of phosphatidylinositol 3-kinase in the anti-phosphotyrosine and anti-IRS-1 immunoprecipitates, the activation of mitogen-activated protein (MAP) kinase, and biological actions were also impaired. |
| 207 | 8393870 | In addition, although the deletion of residues 954-965 severely impaired insulin internalization, the deletion of NPXY (957-960), the internalization signal of the low density lipoprotein receptor, did not affect internalization. |
| 208 | 8393870 | These data suggest that: 1) Tyr960 is important for the recognition of pp185/IRS-1, the association of phosphatidylinositol 3-kinase with pp185/IRS-1, and the activation of MAP kinase; 2) MAP kinase may lie downstream of pp185/IRS-1 in insulin's signal transduction; and 3) the juxtamembrane domain, but not NPXY or individual tyrosines, is important for insulin internalization. |
| 209 | 8393870 | In CHO-Y960F cells, tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1), the activation of phosphatidylinositol 3-kinase in the anti-phosphotyrosine and anti-IRS-1 immunoprecipitates, the activation of mitogen-activated protein (MAP) kinase, and biological actions were also impaired. |
| 210 | 8393870 | In addition, although the deletion of residues 954-965 severely impaired insulin internalization, the deletion of NPXY (957-960), the internalization signal of the low density lipoprotein receptor, did not affect internalization. |
| 211 | 8393870 | These data suggest that: 1) Tyr960 is important for the recognition of pp185/IRS-1, the association of phosphatidylinositol 3-kinase with pp185/IRS-1, and the activation of MAP kinase; 2) MAP kinase may lie downstream of pp185/IRS-1 in insulin's signal transduction; and 3) the juxtamembrane domain, but not NPXY or individual tyrosines, is important for insulin internalization. |
| 212 | 8413261 | Insulin-stimulated oocyte maturation requires insulin receptor substrate 1 and interaction with the SH2 domains of phosphatidylinositol 3-kinase. |
| 213 | 8413261 | Xenopus oocytes from unprimed frogs possess insulin-like growth factor I (IGF-I) receptors but lack insulin and IGF-I receptor substrate 1 (IRS-1), the endogenous substrate of this kinase, and fail to show downstream responses to hormonal stimulation. |
| 214 | 8413261 | Microinjection of recombinant IRS-1 protein enhances insulin-stimulated phosphatidylinositol (PtdIns) 3-kinase activity and restores the germinal vesicle breakdown response. |
| 215 | 8413261 | Activation of PtdIns 3-kinase results from formation of a complex between phosphorylated IRS-1 and the p85 subunit of PtdIns 3-kinase. |
| 216 | 8413261 | Microinjection of a phosphonopeptide containing a pYMXM motif with high affinity for the src homology 2 (SH2) domain of PtdIns 3-kinase p85 inhibits IRS-1 association with and activation of the PtdIns 3-kinase. |
| 217 | 8413261 | Formation of the IRS-1-PtdIns 3-kinase complex and insulin-stimulated PtdIns 3-kinase activation are also inhibited by microinjection of a glutathione S-transferase fusion protein containing the SH2 domain of p85. |
| 218 | 8413261 | These inhibitory effects are specific and are not mimicked by glutathione S-transferase fusion proteins expressing the SH2 domains of ras-GAP or phospholipase C gamma. |
| 219 | 8413261 | Moreover, injection of the SH2 domains of p85, ras-GAP, and phospholipase C gamma do not interfere with progesterone-induced oocyte maturation. |
| 220 | 8413261 | These data demonstrate that phosphorylation of IRS-1 plays an essential role in IGF-I and insulin signaling in oocyte maturation and that this effect occurs through interactions of the phosphorylated YMXM/YXXM motifs of IRS-1 with SH2 domains of PtdIns 3-kinase or some related molecules. |
| 221 | 8527305 | The effects of wortmannin, a potent inhibitor of phosphatidylinositol 3-kinase, on insulin-stimulated glucose transport, GLUT4 translocation, antilipolysis, and DNA synthesis. |
| 222 | 8527305 | Insulin-stimulated translocation of GLUT4 in isolated rat adipocytes was markedly inhibited by wortmannin. |
| 223 | 8527305 | Wortmannin had no effect on either basal or insulin-stimulated glucose utilization in L6 myocytes, a skeletal muscle cell line in which GLUT1 is the predominant transporter isoform. |
| 224 | 8527305 | Wortmannin also partially antagonized the antilipolytic effect of insulin on adenosine deaminase-stimulated lipolysis in isolated rat adipocytes. |
| 225 | 8527305 | We conclude that PI 3-kinase activation is necessary for maximum insulin-stimulated glucose transport, translocation of GLUT4, antilipolysis and DNA synthesis. |
| 226 | 8591706 | Wortmannin is known to be an inhibitor of myosin light chain kinase and phosphatidylinositol 3-kinase (PI 3-kinase) (J. |
| 227 | 8611143 | The phosphatidylinositol 3-kinase inhibitor, wortmannin, inhibits insulin-induced activation of phosphatidylcholine hydrolysis and associated protein kinase C translocation in rat adipocytes. |
| 228 | 8611143 | We questioned whether phosphatidylinositol 3-kinase (PI 3-kinase) and protein kinase C (PKC) function as interrelated signalling mechanisms during insulin action in rat adipocytes. |
| 229 | 8611143 | Insulin rapidly activated a phospholipase D that hydrolyses phosphatidylcholine (PC), and this activation was accompanied by increases in diacylglycerol and translocative activation of PKC-alpha and PKC-beta in the plasma membrane. |
| 230 | 8611143 | Wortmannin, an apparently specific PI 3-kinase inhibitor, inhibited insulin-stimulated, phospholipase D-dependent PC hydrolysis and subsequent translocation of PKC-alpha and PKC-beta to the plasma membrane. |
| 231 | 8611143 | Our findings suggest that insulin acts through PI 3-kinase to activate a PC-specific phospholipase D and causes the translocative activation of PKC-alpha and PKC-beta in plasma membranes of rat adipocytes. |
| 232 | 8611143 | The phosphatidylinositol 3-kinase inhibitor, wortmannin, inhibits insulin-induced activation of phosphatidylcholine hydrolysis and associated protein kinase C translocation in rat adipocytes. |
| 233 | 8611143 | We questioned whether phosphatidylinositol 3-kinase (PI 3-kinase) and protein kinase C (PKC) function as interrelated signalling mechanisms during insulin action in rat adipocytes. |
| 234 | 8611143 | Insulin rapidly activated a phospholipase D that hydrolyses phosphatidylcholine (PC), and this activation was accompanied by increases in diacylglycerol and translocative activation of PKC-alpha and PKC-beta in the plasma membrane. |
| 235 | 8611143 | Wortmannin, an apparently specific PI 3-kinase inhibitor, inhibited insulin-stimulated, phospholipase D-dependent PC hydrolysis and subsequent translocation of PKC-alpha and PKC-beta to the plasma membrane. |
| 236 | 8611143 | Our findings suggest that insulin acts through PI 3-kinase to activate a PC-specific phospholipase D and causes the translocative activation of PKC-alpha and PKC-beta in plasma membranes of rat adipocytes. |
| 237 | 8628286 | Insulin receptor substrate 1 binds two novel splice variants of the regulatory subunit of phosphatidylinositol 3-kinase in muscle and brain. |
| 238 | 8628286 | We have identified two novel alternatively spliced forms of the p85alpha regulatory subunit of phosphatidylinositol (PI) 3-kinase by expression screening of a human skeletal muscle library with phosphorylated baculovirus- produced human insulin receptor substrate 1. |
| 239 | 8628286 | Both p85 and p85/AS53 bind to p110 in coprecipitation experiments, but p85alpha itself appears to have preferential binding to insulin receptor substrate 1 following insulin stimulation. |
| 240 | 8644999 | Addition of zinc chloride to bombesin-sensitive Swiss 3T3 mouse fibroblasts induced a fourfold stimulation in the cytosolic myelin basic protein kinase activity. |
| 241 | 8644999 | The kinase activity coeluted with p42 MAP kinase using chromatography on Mono-Q ion exchange. |
| 242 | 8644999 | Immunoprecipitation against the p85 subunit of phosphatidylinositol 3-kinase resulted in the appearance of two phosphotyrosine-containing proteins, 100 and 115 kDa, in extracts from cells treated with zinc or epidermal growth factor, indicating that the tyrosine phosphorylation was recognized by the corresponding SH2-domains. |
| 243 | 8644999 | The present study demonstrates that extracellular zinc has the potential to partially mimic the action of growth factors on intracellular MAP kinase activation and protein tyrosine phosphorylation. |
| 244 | 8663361 | Okadaic acid exerts a full insulin-like effect on glucose transport and glucose transporter 4 translocation in human adipocytes. |
| 245 | 8663361 | The effects of the serine/threonine phosphatase inhibitor, okadaic acid, and insulin on glucose transport activity, glucose transporter 4 translocation to the plasma membrane, and the signaling pathway of insulin were examined in human adipocytes. |
| 246 | 8663361 | Both insulin alone and okadaic acid alone stimulated the translocation of glucose transporter 4 to the plasma membrane. |
| 247 | 8663361 | Insulin, but not okadaic acid, stimulated phosphatidylinositol 3-kinase (PI 3-kinase) activity, and wortmannin completely inhibited the effect of insulin on glucose transport. |
| 248 | 8663361 | When the cells were incubated with both agents, okadaic acid inhibited insulin-stimulated PI 3-kinase activity but did not block the association of the p85 or p110 subunits of PI 3-kinase with insulin receptor substrate 1. |
| 249 | 8663361 | Insulin-stimulated tyrosine phosphorylation of insulin receptor substrate 1 was only slightly reduced (15-30%) by okadaic acid. |
| 250 | 8666133 | Wortmannin inhibits insulin secretion in pancreatic islets and beta-TC3 cells independent of its inhibition of phosphatidylinositol 3-kinase. |
| 251 | 8666133 | Cholinergic agonists amplify insulin release by several pathways, including activation of phospholipase C, which hydrolyzes membrane polyphosphoinositides. |
| 252 | 8666135 | Effect of IGF-I on phosphatidylinositol 3-kinase in soleus muscle of lean and insulin-resistant obese mice. |
| 253 | 8690802 | Acute regulation by insulin of phosphatidylinositol-3-kinase, Rad, Glut 4, and lipoprotein lipase mRNA levels in human muscle. |
| 254 | 8690802 | Using reverse transcription-competitive PCR, we have measured the mRNAs encoding the two insulin receptor variants, the insulin receptor substrate-1, the p85alpha subunit of phosphatidylinositol-3-kinase, Ras associated to diabetes (Rad), the glucose transporter Glut 4, glycogen synthase, 6-phosphofructo-l-kinase, lipoprotein lipase, and the hormone-sensitive lipase. |
| 255 | 8690802 | Insulin infusion induced a significant increase in the mRNA level of Glut 4 (+56 +/- 13%), Rad (+96 +/- 25%), the p85alpha subunit of phosphatidylinositol-3-kinase (+92 +/- 18%) and a decrease in the lipoprotein lipase mRNA level (-49 +/- 5%), while the abundance of the other mRNAs was unaffected. |
| 256 | 8690802 | These results demonstrate an acute coordinated regulation by insulin of the expression of genes coding key proteins involved in its action in human skeletal muscle and suggest that Rad and the p85alpha regulatory subunit of phosphatidylinositol-3-kinase can be added to the list of the genes controlled by insulin. |
| 257 | 8690802 | Acute regulation by insulin of phosphatidylinositol-3-kinase, Rad, Glut 4, and lipoprotein lipase mRNA levels in human muscle. |
| 258 | 8690802 | Using reverse transcription-competitive PCR, we have measured the mRNAs encoding the two insulin receptor variants, the insulin receptor substrate-1, the p85alpha subunit of phosphatidylinositol-3-kinase, Ras associated to diabetes (Rad), the glucose transporter Glut 4, glycogen synthase, 6-phosphofructo-l-kinase, lipoprotein lipase, and the hormone-sensitive lipase. |
| 259 | 8690802 | Insulin infusion induced a significant increase in the mRNA level of Glut 4 (+56 +/- 13%), Rad (+96 +/- 25%), the p85alpha subunit of phosphatidylinositol-3-kinase (+92 +/- 18%) and a decrease in the lipoprotein lipase mRNA level (-49 +/- 5%), while the abundance of the other mRNAs was unaffected. |
| 260 | 8690802 | These results demonstrate an acute coordinated regulation by insulin of the expression of genes coding key proteins involved in its action in human skeletal muscle and suggest that Rad and the p85alpha regulatory subunit of phosphatidylinositol-3-kinase can be added to the list of the genes controlled by insulin. |
| 261 | 8690802 | Acute regulation by insulin of phosphatidylinositol-3-kinase, Rad, Glut 4, and lipoprotein lipase mRNA levels in human muscle. |
| 262 | 8690802 | Using reverse transcription-competitive PCR, we have measured the mRNAs encoding the two insulin receptor variants, the insulin receptor substrate-1, the p85alpha subunit of phosphatidylinositol-3-kinase, Ras associated to diabetes (Rad), the glucose transporter Glut 4, glycogen synthase, 6-phosphofructo-l-kinase, lipoprotein lipase, and the hormone-sensitive lipase. |
| 263 | 8690802 | Insulin infusion induced a significant increase in the mRNA level of Glut 4 (+56 +/- 13%), Rad (+96 +/- 25%), the p85alpha subunit of phosphatidylinositol-3-kinase (+92 +/- 18%) and a decrease in the lipoprotein lipase mRNA level (-49 +/- 5%), while the abundance of the other mRNAs was unaffected. |
| 264 | 8690802 | These results demonstrate an acute coordinated regulation by insulin of the expression of genes coding key proteins involved in its action in human skeletal muscle and suggest that Rad and the p85alpha regulatory subunit of phosphatidylinositol-3-kinase can be added to the list of the genes controlled by insulin. |
| 265 | 8690802 | Acute regulation by insulin of phosphatidylinositol-3-kinase, Rad, Glut 4, and lipoprotein lipase mRNA levels in human muscle. |
| 266 | 8690802 | Using reverse transcription-competitive PCR, we have measured the mRNAs encoding the two insulin receptor variants, the insulin receptor substrate-1, the p85alpha subunit of phosphatidylinositol-3-kinase, Ras associated to diabetes (Rad), the glucose transporter Glut 4, glycogen synthase, 6-phosphofructo-l-kinase, lipoprotein lipase, and the hormone-sensitive lipase. |
| 267 | 8690802 | Insulin infusion induced a significant increase in the mRNA level of Glut 4 (+56 +/- 13%), Rad (+96 +/- 25%), the p85alpha subunit of phosphatidylinositol-3-kinase (+92 +/- 18%) and a decrease in the lipoprotein lipase mRNA level (-49 +/- 5%), while the abundance of the other mRNAs was unaffected. |
| 268 | 8690802 | These results demonstrate an acute coordinated regulation by insulin of the expression of genes coding key proteins involved in its action in human skeletal muscle and suggest that Rad and the p85alpha regulatory subunit of phosphatidylinositol-3-kinase can be added to the list of the genes controlled by insulin. |
| 269 | 8770859 | The effects of insulin and IGF-1 were completely blocked by inhibitors of either tyrosine kinase (genestein) or nitric oxide synthase (L-NAME). |
| 270 | 8770859 | Wortmannin (an inhibitor of phosphatidylinositol 3-kinase [PI 3-kinase]) inhibited insulin-stimulated production of NO by approximately 50%. |
| 271 | 8798502 | Rad is a Ras-like GTPase that was isolated by subtraction cloning of human muscle and shown to have increased expression in some individuals with Type II diabetes. |
| 272 | 8798502 | To ascertain the potential role of Rad in insulin-mediated signaling, we have overexpressed Rad in myocyte and adipocyte cell lines. |
| 273 | 8798502 | This occurred despite unaltered levels of glucose transporter expression, with no detectable change in Glut4 translocation and with no alteration in insulin receptor or substrate phosphorylation or phosphatidylinositol 3-kinase activity. |
| 274 | 8798677 | The pleckstrin homology domain is the principal link between the insulin receptor and IRS-1. |
| 275 | 8798677 | Interaction domains located in the NH2 terminus of IRS-1 mediate its recognition by the insulin receptor. |
| 276 | 8798677 | Alignment of IRS-1 and IRS-2 reveals two homology regions: the IH1(PH) contains a pleckstrin homology (PH) domain, and the IH2(PTB) contains a phosphotyrosine binding (PTB) domain. |
| 277 | 8798677 | Peptide competition experiments demonstrated that the IH2(PTB) in IRS-2, like the corresponding domain in IRS-1, binds directly to peptides containing NPXY motifs. |
| 278 | 8798677 | In 32D cells the IH1(PH) was essential for insulin-stimulated tyrosine phosphorylation of IRS-1 and insulin-stimulated phosphatidylinositol 3-kinase activity and p70(s6k) phosphorylation. |
| 279 | 8798677 | In contrast, the IH2(PTB) and the SAIN regions were not required for these insulin actions; however, the IH2(PTB) improved the coupling between IRS-1 and the insulin receptor. |
| 280 | 8798677 | Overexpression of the insulin receptor in 32DIR cells increased IRS-1 tyrosine phosphorylation and mediated insulin-stimulated DNA synthesis. |
| 281 | 8798677 | Thus, the PH and PTB domains equally couple IRS-1 to high levels of insulin receptor normally expressed in most cells, whereas at low levels of insulin receptors the PTB domain is inefficient and the PH domain is essential for a productive interaction. |
| 282 | 8903320 | Characterization of vascular endothelial growth factor's effect on the activation of protein kinase C, its isoforms, and endothelial cell growth. |
| 283 | 8903320 | VEGF induced concentration- and time-dependent increases in protein kinase C (PKC) activation with a maximum of 2.2-fold above the basal level at 5 x 10(-10) M within 10 min as measured both by in situ and translocation assays. |
| 284 | 8903320 | In addition, VEGF increased phosphatidylinositol 3-kinase activity 2.1-fold which was inhibited by wortmannin, a phosphatidylinositol 3-kinase inhibitor, without decreasing the VEGF-induced increase in PKC activity or endothelial cell growth. |
| 285 | 8903320 | In contrast, antisense PKC-alpha oligonucleotides enhanced VEGF-stimulated cell growth with a simultaneous decrease of 70% in PKC-alpha protein content. |
| 286 | 8903320 | Thus, VEGF appears to mediate its mitogenic effects partly through the activation of the PLCgamma and PKC pathway, involving predominately PKC-beta isoform activation in endothelial cells. |
| 287 | 8910437 | We have reported previously that substitution of the transmembrane domain of the insulin receptor with that of the erbB-2 oncogene (IRerbV-->E) results in constitutive activation of the insulin receptor kinase. |
| 288 | 8910437 | Compared to NIH3T3 cells overexpressing wild-type insulin receptors (IRwt), cells overexpressing IRerbV-->E displayed a decrease in IRS-1 protein content by 55%, but basal tyrosine phosphorylation of IRS-1 was increased. |
| 289 | 8910437 | This resulted in an increased association of IRS-1 with the p85 subunit of phosphatidylinositol 3-kinase, increased phosphatidylinositol 3-kinase activity in anti-IRS-1 immunoprecipitates, constitutive activation of p70 S6 protein kinase, and an increased association of Grb2 with Shc in the absence of ligand. |
| 290 | 8910437 | However, Grb2 association with IRS-1 could not be detected in the basal or insulin-stimulated states, and mitogen-activated protein kinase (MAPK) activity could not be stimulated by insulin, epidermal growth factor, or platelet-derived growth factor. |
| 291 | 8910437 | With decreased IRS-1 content, tyrosine phosphorylation of IRS-1 was decreased by over 75%, leading to decreased IRS-1-associated PI 3-kinase and Grb2. |
| 292 | 8910437 | In addition, Grb2 association with Shc and activation of MAPK and the p70 S6 kinase were insensitive to insulin stimulation. |
| 293 | 8910437 | By contrast, association of Grb2 with Shc and activation of MAPK, but not the p70 S6 kinase, could be stimulated by epidermal growth factor or platelet-derived growth factor. |
| 294 | 8922368 | In parallel to insulin action, the stimulation of glucose uptake by thioctic acid was abolished by wortmannin, an inhibitor of phosphatidylinositol 3-kinase, in both cell lines. |
| 295 | 8922368 | The molar content of GLUT1 and GLUT4 transporters was measured in both cell lines. 3T3-L1 adipocytes were shown to have >10 times more glucose transporters but similar ratios of GLUT4:GLUT1 than L6 myotubes. |
| 296 | 8922368 | Its stimulatory effect on glucose uptake was associated with an intracellular redistribution of GLUT1 and GLUT4 glucose transporters, similar to that caused by insulin, with minimal effects on GLUT3 transporters. |
| 297 | 8940115 | cAMP counter-regulates insulin-mediated protein phosphatase-2A inactivation in rat skeletal muscle cells. |
| 298 | 8940115 | In this study, we examined the mechanism of recently reported inactivation of protein phosphatase-2A (PP-2A) by insulin (Srinivasan, M., and Begum, N. (1994) J. |
| 299 | 8940115 | Exposure of L6 myotubes to insulin resulted in a rapid inhibition of PP-2A that was accompanied by a 3-fold increase in the phosphotyrosine content of the immunoprecipitated PP-2A catalytic subunit. |
| 300 | 8940115 | Pretreatment with (Sp)-cAMP, a cAMP agonist, completely blocked insulin-mediated inhibition of PP-2A activity and decreased the tyrosine phosphorylation of PP-2A catalytic subunit to control levels. |
| 301 | 8940115 | Wortmannin, a phosphatidylinositol 3-kinase inhibitor, and rapamycin, an inhibitor of 70-kDa S6 kinase activation, prevented insulin-mediated inactivation of PP-2A, suggesting that these pathways may participate in insulin-mediated phosphorylation and inactivation of PP-2A. |
| 302 | 8940115 | These results show that insulin signaling results in a rapid inactivation of PP-2A by increased tyrosine phosphorylation and cAMP agonists counter-regulate insulin's effect on PP-2A by decreasing phosphorylation, presumably via an activated phosphatase. |
| 303 | 8940181 | One of the peptides, termed peptide HC, whose structure corresponds to residues 1293-1307 of the insulin proreceptor sequence, enhanced insulin-stimulated autophosphorylation of the insulin receptor in cell-free systems and in semipermeabilized Chinese hamster ovary (CHO) cells that had been transfected with an expression plasmid encoding the human insulin receptor (CHO/HIRc) at concentrations where there was no detectable effect on basal autophosphorylation levels or on receptor dephosphorylation. |
| 304 | 8940181 | A lipophilic analogue of peptide HC, stearyl peptide HC, added to intact CHO/HIRc cells enhanced significantly insulin-stimulated insulin receptor autophosphorylation while having no effect on ligand-stimulated receptor phosphorylation in CHO cells overexpressing either the IGF-1 receptor or epidermal growth factor receptor. |
| 305 | 8940181 | Addition of stearyl peptide HC to CHO/HIRc cells resulted in a 2.4 +/- 0.3-fold increase in the amount of insulin-stimulated phosphatidylinositol 3-kinase detected in anti-IRS-1 immunoprecipitates and a 2.1 +/- 0.6-fold increase in the levels of tyrosine phosphorylation of mitogen-activated protein kinase in response to insulin. |
| 306 | 8940181 | However, there was little binding, if any, of the peptide with the IGF-1 receptors or the epidermal growth factor receptors. |
| 307 | 8971075 | Glucagon (via the second messenger cAMP), retinoic acid, and glucocorticoids stimulate transcription of the PEPCK gene, whereas insulin and phorbol esters have a dominant inhibitory effect. |
| 308 | 8971075 | Wortmannin, an inhibitor of 1-phosphatidylinositol 3-kinase (PI 3-kinase), blocks the inhibition of glucocorticoid and cAMP-induced PEPCK gene transcription by insulin; however, it has no effect on the inhibition elicited by oxidative or chemical stress. |
| 309 | 8971075 | The reactivating kinase (RK, also known as p38 mitogen activated protein kinase) is induced by insulin, hydrogen peroxide, or sodium meta-arsenite in hepatoma cells, and these effects are blocked by SB203580, a selective inhibitor of RK. |
| 310 | 8971075 | Thus, although RK has a role in the regulation of lymphokine gene expression in monocytes, it is not required for the regulation of PEPCK expression by either insulin or oxidative and chemical stress in hepatoma cells. |
| 311 | 8983814 | IRS-1 binds several Src homology 2 (SH2) proteins through its multiple tyrosine phosphorylation sites: phosphatidylinositol 3-kinase (PI 3-kinase), the Ras guanine-nucleotide-releasing complex Grb2-SOS, the tyrosine phosphatase Syp, and the adapter protein Nck. |
| 312 | 8983814 | IRS-1 is essential for many, but not all of the insulin's biological responses. |
| 313 | 9006804 | Effect of glucose, insulin, and insulin-like growth factor-I on glucose transport activity in cultured rat vascular smooth muscle cells. |
| 314 | 9006804 | Glucose transport activity in cultured rat vascular smooth muscle cells (VSMCs) was examined under various concentrations of D-glucose, insulin, and insulin-like growth factor-I (IGF-I). |
| 315 | 9006804 | Wortmannin, an inhibitor of phosphatidylinositol 3-kinase (PI3-kinase), inhibited the uptake of glucose stimulated by insulin or IGF-I in a dose-dependent manner. |
| 316 | 9006804 | Activation of wortmannin-sensitive PI3-kinase may be involved in the signaling pathways of the insulin- and IGF-I-stimulated glucose uptake in VSMCs. |
| 317 | 9006901 | Splice variants of an insulin and growth factor receptor-binding protein with PH and SH2 domains. |
| 318 | 9006901 | cDNA clones encoding human (h) Grb7 and a previously unknown protein with high homology to hGrb-IR and mGrb10 (where m indicates mouse) were found by screening expressed sequence tag data bases. hGrb7 mRNA expression is greatest in pancreas and restricted to a few other tissues. |
| 319 | 9006901 | In cells, Grb-IRbeta/Grb10 protein translocates from cytosol to membrane upon insulin stimulation, most likely due to direct interactions with the insulin receptor. |
| 320 | 9006901 | Studies with mutated receptors and synthetic phosphopeptides show that the hGrb-IRbeta/Grb10 SH2 domain binds at least two sites in the insulin receptor: the kinase activation loop > the juxtamembrane site. hGrb-IRbeta/Grb10 also binds a 135-kDa phosphoprotein in unstimulated 3T3-L1 adipocytes; binding is reduced upon insulin stimulation. |
| 321 | 9006901 | In addition, the c-Abl SH3 domain binds Grb-IR/Grb10, whereas Fyn, phosphatidylinositol 3-kinase p85, and Grb2 SH3 domains do not. |
| 322 | 9006901 | The site of c-Abl SH3 domain interaction is highly conserved within the Grb-IR/Grb10/Grb7/Grb14 family. hGrb-IRbeta/Grb10 also binds platelet-derived growth factor and epidermal growth factor receptors, suggesting a broader role in the signaling pathways of numerous receptors. |
| 323 | 9006901 | We conclude that hGrb-IRbeta/Grb10 is a widely expressed, PH and SH2 domain-containing, SH3 domain-binding protein that functions downstream from activated insulin and growth factor receptors. |
| 324 | 9032108 | Identification of a common amino acid polymorphism in the p85alpha regulatory subunit of phosphatidylinositol 3-kinase: effects on glucose disappearance constant, glucose effectiveness, and the insulin sensitivity index. |
| 325 | 9032108 | Phosphatidylinositol 3-kinase (PI3-K) may regulate the basal plasma membrane glucose transporter recycling and the organization of the transporter intracellular pool in addition to being an insulin signal for translocation of glucose transporters to the plasma membrane. |
| 326 | 9032108 | The objectives of the present study were to examine for genetic variability in the human regulatory p85alpha subunit of PI3-K, to look for an association between gene variants and NIDDM in a case-control study, and to relate identified variability to potential changes in whole-body insulin sensitivity and glucose turnover in a phenotype study. |
| 327 | 9032108 | Single-strand conformational polymorphism and heteroduplex analysis of the coding region of the regulatory p85alpha subunit in cDNA isolated from human muscle tissue from 70 insulin-resistant NIDDM patients and 12 control subjects revealed three silent polymorphisms and a missense mutation at nucleotide position 1020 (G-->A), changing a Met to Ile at codon 326. |
| 328 | 9032108 | In conclusion, a codon 326Met-->Ile variant in the gene encoding the PI3-K p85alpha regulatory subunit is found in 31% of a random sample of young healthy Caucasians. |
| 329 | 9032108 | Identification of a common amino acid polymorphism in the p85alpha regulatory subunit of phosphatidylinositol 3-kinase: effects on glucose disappearance constant, glucose effectiveness, and the insulin sensitivity index. |
| 330 | 9032108 | Phosphatidylinositol 3-kinase (PI3-K) may regulate the basal plasma membrane glucose transporter recycling and the organization of the transporter intracellular pool in addition to being an insulin signal for translocation of glucose transporters to the plasma membrane. |
| 331 | 9032108 | The objectives of the present study were to examine for genetic variability in the human regulatory p85alpha subunit of PI3-K, to look for an association between gene variants and NIDDM in a case-control study, and to relate identified variability to potential changes in whole-body insulin sensitivity and glucose turnover in a phenotype study. |
| 332 | 9032108 | Single-strand conformational polymorphism and heteroduplex analysis of the coding region of the regulatory p85alpha subunit in cDNA isolated from human muscle tissue from 70 insulin-resistant NIDDM patients and 12 control subjects revealed three silent polymorphisms and a missense mutation at nucleotide position 1020 (G-->A), changing a Met to Ile at codon 326. |
| 333 | 9032108 | In conclusion, a codon 326Met-->Ile variant in the gene encoding the PI3-K p85alpha regulatory subunit is found in 31% of a random sample of young healthy Caucasians. |
| 334 | 9032108 | Identification of a common amino acid polymorphism in the p85alpha regulatory subunit of phosphatidylinositol 3-kinase: effects on glucose disappearance constant, glucose effectiveness, and the insulin sensitivity index. |
| 335 | 9032108 | Phosphatidylinositol 3-kinase (PI3-K) may regulate the basal plasma membrane glucose transporter recycling and the organization of the transporter intracellular pool in addition to being an insulin signal for translocation of glucose transporters to the plasma membrane. |
| 336 | 9032108 | The objectives of the present study were to examine for genetic variability in the human regulatory p85alpha subunit of PI3-K, to look for an association between gene variants and NIDDM in a case-control study, and to relate identified variability to potential changes in whole-body insulin sensitivity and glucose turnover in a phenotype study. |
| 337 | 9032108 | Single-strand conformational polymorphism and heteroduplex analysis of the coding region of the regulatory p85alpha subunit in cDNA isolated from human muscle tissue from 70 insulin-resistant NIDDM patients and 12 control subjects revealed three silent polymorphisms and a missense mutation at nucleotide position 1020 (G-->A), changing a Met to Ile at codon 326. |
| 338 | 9032108 | In conclusion, a codon 326Met-->Ile variant in the gene encoding the PI3-K p85alpha regulatory subunit is found in 31% of a random sample of young healthy Caucasians. |
| 339 | 9032108 | Identification of a common amino acid polymorphism in the p85alpha regulatory subunit of phosphatidylinositol 3-kinase: effects on glucose disappearance constant, glucose effectiveness, and the insulin sensitivity index. |
| 340 | 9032108 | Phosphatidylinositol 3-kinase (PI3-K) may regulate the basal plasma membrane glucose transporter recycling and the organization of the transporter intracellular pool in addition to being an insulin signal for translocation of glucose transporters to the plasma membrane. |
| 341 | 9032108 | The objectives of the present study were to examine for genetic variability in the human regulatory p85alpha subunit of PI3-K, to look for an association between gene variants and NIDDM in a case-control study, and to relate identified variability to potential changes in whole-body insulin sensitivity and glucose turnover in a phenotype study. |
| 342 | 9032108 | Single-strand conformational polymorphism and heteroduplex analysis of the coding region of the regulatory p85alpha subunit in cDNA isolated from human muscle tissue from 70 insulin-resistant NIDDM patients and 12 control subjects revealed three silent polymorphisms and a missense mutation at nucleotide position 1020 (G-->A), changing a Met to Ile at codon 326. |
| 343 | 9032108 | In conclusion, a codon 326Met-->Ile variant in the gene encoding the PI3-K p85alpha regulatory subunit is found in 31% of a random sample of young healthy Caucasians. |
| 344 | 9032113 | Insulin receptor substrate-1 phosphorylation and phosphatidylinositol 3-kinase activity in skeletal muscle from NIDDM subjects after in vivo insulin stimulation. |
| 345 | 9032113 | A rise in serum insulin levels from approximately 60 to approximately 650 pmol/l increased IRS-1 tyrosine phosphorylation sixfold over basal levels in control muscle (P < 0.01), whereas no significant increase was noted in NIDDM muscle. |
| 346 | 9032113 | The present findings couple both reduced insulin-stimulated IRS-1 tyrosine phosphorylation and PI 3-kinase activity to the impaired insulin-stimulated glucose transport in skeletal muscle from lean-to-moderately obese NIDDM subjects. |
| 347 | 9032279 | Differential signaling by insulin receptor substrate 1 (IRS-1) and IRS-2 in IRS-1-deficient cells. |
| 348 | 9032279 | Mice made insulin receptor substrate 1 (IRS-1) deficient by targeted gene knockout exhibit growth retardation and abnormal glucose metabolism due to resistance to the actions of insulin-like growth factor 1 (IGF-1) and insulin (E. |
| 349 | 9032279 | Embryonic fibroblasts and 3T3 cell lines derived from IRS-1-deficient embryos exhibit no IGF-1-stimulated IRS-1 phosphorylation or IRS-1-associated phosphatidylinositol 3-kinase (PI 3-kinase) activity but exhibit normal phosphorylation of IRS-2 and Shc and normal IRS-2-associated PI 3-kinase activity. |
| 350 | 9032279 | IRS-1 deficiency results in a 70 to 80% reduction in IGF-1-stimulated cell growth and parallel decreases in IGF-1-stimulated S-phase entry, PI 3-kinase activity, and induction of the immediate-early genes c-fos and egr-1 but unaltered activation of the mitogen-activated protein kinases ERK 1 and ERK 2. |
| 351 | 9032279 | Expression of IRS-1 in IRS-1-deficient cells by retroviral gene transduction restores IGF-1-stimulated mitogenesis, PI 3-kinase activation, and c-fos and egr-1 induction in proportion to the level of reconstitution. |
| 352 | 9032279 | Increasing the level of IRS-2 in these cells by using a retrovirus reconstitutes IGF-1 activation of PI 3-kinase and immediate-early gene expression to the same degree as expression of IRS-1; however, IRS-2 overexpression has only a minor effect on IGF-1 stimulation of cell cycle progression. |
| 353 | 9032279 | These results indicate that IRS-1 is not necessary for activation of ERK 1 and ERK 2 and that activation of ERK 1 and ERK 2 is not sufficient for IGF-1-stimulated activation of c-fos and egr-1. |
| 354 | 9032279 | These data also provide evidence that IRS-1 and IRS-2 are not functionally interchangeable signaling intermediates for stimulation of mitogenesis despite their highly conserved structure and many common functions such as activating PI 3-kinase and early gene expression. |
| 355 | 9054447 | Specific increase in p85alpha expression in response to dexamethasone is associated with inhibition of insulin-like growth factor-I stimulated phosphatidylinositol 3-kinase activity in cultured muscle cells. |
| 356 | 9054447 | The stimulation of phosphatidylinositol (PI) 3-kinase by insulin-like growth factor I (IGF-I) in L6 cultured skeletal muscle cells is inhibited by the glucocorticoid dexamethasone. |
| 357 | 9054447 | The objective of this study was to investigate the mechanism of dexamethasone action by determining its effects on the expression of the p85alpha and p85beta regulatory subunit isoforms of PI 3-kinase, their coupling with the p110 catalytic subunit, and their association with insulin receptor substrate 1 (IRS-1) in response to IGF-I stimulation. |
| 358 | 9054447 | Dexamethasone induced a 300% increase in p85alpha protein content in the L6 cultured myoblast cell line, whereas it increased p110 content by only 38% and had no effect on p85beta. |
| 359 | 9054447 | Stimulation with IGF-I induced the association of p85alpha and p85beta with IRS-1, and this was accompanied by increased amounts of the p110 catalytic subunit and markedly increased PI 3-kinase activity in IRS-1 immunoprecipitates. |
| 360 | 9054447 | In cells treated with dexamethasone, greater amounts of p85alpha and lower amounts of p85beta, respectively, were found in IRS-1 immunoprecipitates, such that the alpha/beta ratio was markedly higher than in control cells. |
| 361 | 9054447 | In spite of the increase in both total and IRS-1-associated p85alpha following dexamethasone treatment, IRS-1-associated p110 catalytic subunit and PI 3-kinase activity were decreased by approximately 50%. |
| 362 | 9054447 | Thus, dexamethasone induces a specific increase in expression of the p85alpha regulatory subunit that is not associated with a coordinate increase in the p110 catalytic subunit of PI 3-kinase. |
| 363 | 9054447 | As a consequence, in dexamethasone-treated cells, p85alpha that is not coupled with p110 competes with both p85alpha.p110 and p85beta.p110 complexes for association with IRS-1, leading to increased p85alpha but decreased p85beta, p110, and PI 3-kinase activity in IRS-1 immunoprecipitates. |
| 364 | 9082023 | Glucose-induced insulin secretion is impaired and insulin-induced phosphorylation of the insulin receptor and insulin receptor substrate-1 are increased in protein-deficient rats. |
| 365 | 9082023 | Immunoblotting and immunoprecipitation were used to study the phosphorylation of the insulin receptor and the insulin receptor substrate-1 as well as the insulin receptor substrate-1-p85 subunit of phosphatidylinositol 3-kinase association in response to insulin. |
| 366 | 9082023 | Therefore, we conclude that a decreased glucose-induced insulin secretion in pancreatic islets from protein-malnourished rats is responsible, at least in part, for an increased phosphorylation of the insulin receptor, insulin receptor substrate-1 and its association with phosphatidylinositol 3-kinase. |
| 367 | 9082023 | Glucose-induced insulin secretion is impaired and insulin-induced phosphorylation of the insulin receptor and insulin receptor substrate-1 are increased in protein-deficient rats. |
| 368 | 9082023 | Immunoblotting and immunoprecipitation were used to study the phosphorylation of the insulin receptor and the insulin receptor substrate-1 as well as the insulin receptor substrate-1-p85 subunit of phosphatidylinositol 3-kinase association in response to insulin. |
| 369 | 9082023 | Therefore, we conclude that a decreased glucose-induced insulin secretion in pancreatic islets from protein-malnourished rats is responsible, at least in part, for an increased phosphorylation of the insulin receptor, insulin receptor substrate-1 and its association with phosphatidylinositol 3-kinase. |
| 370 | 9108124 | Insulin receptor substrate (IRS) 1 is reduced and IRS-2 is the main docking protein for phosphatidylinositol 3-kinase in adipocytes from subjects with non-insulin-dependent diabetes mellitus. |
| 371 | 9108124 | The large docking protein IRS-1 is a major substrate for the insulin receptor and other tyrosine kinases. |
| 372 | 9108124 | Gene disruption of IRS-1 in mice is associated with an impaired insulin-stimulated glucose disposal in vivo and glucose transport in vitro, but the survival of the animals and residual insulin sensitivity is dependent on the presence of the alternative docking protein IRS-2. |
| 373 | 9108124 | We examined the expression and function of IRS-1 and IRS-2 in adipocytes from healthy and diabetic individuals. |
| 374 | 9108124 | Cells from subjects with non-insulin-dependent diabetes mellitus (NIDDM), but not with insulin-dependent diabetes mellitus, had an impaired insulin effect and a marked reduction (70 +/- 6%) in the expression of IRS-1 protein, whereas IRS-2 was unchanged. |
| 375 | 9108124 | In normal cells, IRS-1 was the main docking protein for the binding and activation of insulin-stimulated PI 3-kinase; IRS-2 was also functional but required a higher insulin concentration for a similar binding and activation of PI 3-kinase. |
| 376 | 9108124 | In contrast in NIDDM cells with a low IRS-1 content, IRS-2 became the main docking protein. |
| 377 | 9133538 | Differential activation of mitogen-activated protein kinase by insulin and epidermal growth factor in 3T3-L1 adipocytes: a possible involvement of PI3-kinase in the activation of the MAP kinase by insulin. |
| 378 | 9133538 | Mitogen-activated protein (MAP) kinase plays crucial roles in cell growth and differentiation. |
| 379 | 9133538 | It has recently been shown that the MAP kinase cascade in growth factor signaling diverges and cross-talks with other signaling pathways. |
| 380 | 9133538 | In the present study, we examined the effects of wortmannin, a specific inhibitor of phosphatidylinositol 3-kinase (PI3-kinase), on the activation of Ras, Raf-1 kinase, and MAP kinase by insulin and epidermal growth factor (EGF). |
| 381 | 9133538 | The effect of LY294002, a structurally distinct PI3-kinase inhibitor, on the activation of Raf-1 kinase by both ligands was also examined. |
| 382 | 9133538 | In 3T3-L1 adipocytes, 25 nmol/l wortmannin inhibited the insulin-induced activation of Raf-1 kinase to the basal level, whereas the same dose of wortmannin had little effect on the EGF-induced activation of Raf-1 kinase. |
| 383 | 9133538 | One hundred micromol/l LY294002 blocked insulin-induced activation of Raf-1 kinase without affecting EGF-induced activation of this kinase. |
| 384 | 9133538 | Twenty-five nmol/l wortmannin inhibited the insulin-induced activation of MAP kinase to the basal level with no effect on the EGF-induced activation of this kinase. |
| 385 | 9133538 | In contrast, in Chinese hamster ovary cells overexpressing the human insulin receptor (CHO-HIR cells), neither wortmannin nor LY294002 inhibited the insulin-induced activation of Raf-1 kinase, and wortmannin had little effect on the activation of MAP kinase by insulin. |
| 386 | 9133538 | These results indicate that 1) PI3-kinase or wortmannin-sensitive molecules are involved in the interaction between activated Ras and Raf-1 kinase in the insulin signaling in 3T3-L1 adipocytes, 2) the involvement of PI3-kinase or wortmannin-sensitive molecules in the insulin-induced activation of MAP kinase appears to be cell-type specific, and 3) differential mechanisms to activate Raf-1 kinase and MAP kinase by insulin and EGF exist. |
| 387 | 9165048 | Mitogen-activated protein kinase and phosphatidylinositol 3-kinase pathways are not sufficient for insulin-like growth factor I-induced mitogenesis and tumorigenesis. |
| 388 | 9165048 | Insulin-like growth factor-I (IGF-I) and insulin are known to activate a signaling cascade involving ras --> kappa raf-1 --> mitogen-activated protein (MAP) kinase kinase (MEK) --> p42/p44 MAP kinase (Erk-1 and -2). |
| 389 | 9165048 | Recent reports suggest that activation of this ras/MAP kinase pathway is involved in mitogenesis and c-fos transcription but is not required for insulin action on metabolic processes such as glycogen synthesis, lipogenesis, and GLUT-4-mediated glucose transport. |
| 390 | 9165048 | To further characterize the role of these tyrosines in IGF-I receptor function, we have used three distinct approaches to examine the ras/MAP kinase pathway in IGF-I-induced mitogenesis and tumorigenesis in NIH-3T3 cells overexpressing wild-type and mutated IGF-I receptors: 1) tyrosine phosphorylation of the MAP kinases Erk-1 and -2; 2), mobility shifts indicative of MAP kinase phosphorylation; and 3) in vitro MAP kinase activation. |
| 391 | 9165048 | By each method we show that the IGF-I-induced MAP kinase phosphorylation/activation and PI 3-kinase activation, are not different between cells overexpressing wild-type IGF-I receptors and cells carrying IGF-I receptors having tyrosine motifs replaced at positions 1250 and 1251. |
| 392 | 9165048 | We conclude that mitogenic and tumorigenic signals involving tyrosine residues in the C-terminal domain of the IGF-I-receptor include pathways other than the MAP kinase and PI 3-kinase pathways. |
| 393 | 9166412 | This was associated with an increase in mRNA levels of insulin, glucagon, and somatostatin, as well as an increase in the insulin protein content and secretion in response to secretagogues. |
| 394 | 9166412 | The activity of PI3K was inversely correlated with the hepatocyte growth factor/scatter factor-induced downregulation or nicotinamideinduced upregulation of islet-specific gene expression, giving support to the role of PI3K, as a negative regulator of endocrine differentiation. |
| 395 | 9166661 | Impact of natural IRS-1 mutations on insulin signals: mutations of IRS-1 in the PTB domain and near SH2 protein binding sites result in impaired function at different steps of IRS-1 signaling. |
| 396 | 9166661 | In this study, we have examined the impact of three natural IRS-1 mutations identified in NIDDM patients (G971R, P170R, and M209T) on insulin signaling. |
| 397 | 9166661 | G971R is located near src homology 2 protein binding sites, and P170R and M209T are located in the phosphotyrosine binding domain of IRS-1. 32D-IR cells, stably overexpressing human insulin receptor, were transfected with wild-type human IRS-1 cDNA (WT) or three mutant IRS-1 cDNAs and analyzed. |
| 398 | 9166661 | Upon insulin stimulation, cells expressing G971R showed a 39% decrease (P < 0.005) in phosphatidylinositol 3-kinase (PI 3-kinase) activity, a 43% decrease (P < 0.01) in binding of the 85-kDa regulatory subunit of PI 3-kinase, and a 22% decrease (P < 0.05) in mitogen-activated protein kinase activity compared with those expressing WT. |
| 399 | 9166661 | After insulin stimulation, cells expressing P170R and M209T showed significant decreases in IRS-1 phosphorylation (37 and 42%, respectively; both P < 0.05) and in IRS-1 binding to the insulin receptor (48 and 53%, respectively; P < 0.01) compared with WT. |
| 400 | 9166661 | G971R showed no changes in IRS-1 phosphorylation and in IRS-1 binding to the insulin receptor compared with WT. |
| 401 | 9166661 | These data suggest that the impaired mitogenic response of P170R and M209T was mainly due to reduced binding to the insulin receptor, whereas the impaired response of G971R was mainly due to reduced association with PI 3-kinase p85. |
| 402 | 9167124 | Prevalence of a polymorphism of the phosphatidylinositol 3-kinase p85 alpha regulatory subunit (codon 326 Met-->Ile) in Japanese NIDDM patients. |
| 403 | 9221053 | At postreceptor steps, phosphatidylinositol 3-kinase (PI3-K) plays an important role in insulin signalling, particularly for the stimulation of glucose transport in muscle and adipocyte. |
| 404 | 9221053 | Insulin activation of PI3-K is markedly diminished in obese mice; starving the obese animals restores normal responses of PI3-K, glucose transport, and glycogen synthesis, to insulin. |
| 405 | 9221053 | At postreceptor steps, phosphatidylinositol 3-kinase (PI3-K) plays an important role in insulin signalling, particularly for the stimulation of glucose transport in muscle and adipocyte. |
| 406 | 9221053 | Insulin activation of PI3-K is markedly diminished in obese mice; starving the obese animals restores normal responses of PI3-K, glucose transport, and glycogen synthesis, to insulin. |
| 407 | 9252480 | Isolated ventricular cardiomyocytes obtained from lean and genetically (fa/fa) obese Zucker rats were used to correlate alterations of insulin-induced glucose transport activation and GLUT-4 translocation to possible defects of the insulin signaling cascade. |
| 408 | 9252480 | Maximal stimulation with insulin was found to produce an unaltered translocation of GLUT-4 to the plasma membrane (4.2- and 3.7-fold increase for lean and obese rats, respectively). |
| 409 | 9252480 | The reduced sensitivity of glucose transport at 8 x 10(-11) M insulin was then found to correlate to a completely blunted response of IRS-1-associated phosphatidylinositol 3-kinase activity in cardiomyocytes from obese rats. |
| 410 | 9252480 | Those data show that cardiac insulin resistance of obesity involves defective insulin signaling at low concentrations of the hormone, whereas GLUT-4 translocation is fully operative in the isolated cell. |
| 411 | 9252480 | It is suggested that hyperphosphorylation of IRS-1 may significantly contribute to the pathogenesis of insulin resistance in the heart. |
| 412 | 9293959 | Isolated adult rat ventricular cardiomyocytes were used to investigate the effects of contractile activity on 3-O-methylglucose transport on the translocation of the insulin-responsive glucose transporter GLUT4, and the possible activation of intermediates of the insulin signaling cascade. |
| 413 | 9293959 | Subcellular fractionation and immunoblotting analysis of GLUT4 distribution indicated that both contraction and insulin induced an identical increase (8-9-fold) of GLUT4 in the plasma membrane with a concomitant decrease (one third) in the microsomal fraction. |
| 414 | 9293959 | However, immunoprecipitation of insulin receptor substrate-1 (IRS-1) showed that the p85 regulatory subunit of phosphatidylinositol-3 kinase did not associate with IRS-1 upon contraction but with a marked stimulated association in response to insulin. |
| 415 | 9293959 | These data suggest the existence of identical insulin- and contraction-recruitable GLUT4 pool. |
| 416 | 9293959 | Contraction-induced signaling may use a limited part of the insulin-signaling cascade, possibly involving IRS-2. |
| 417 | 9293959 | We further suggest that insulin resistance at the level of IRS-1 will not affect contraction-regulated glucose uptake by the heart. |
| 418 | 9295306 | In this study, we examined the potential role of serine/threonine protein phosphatase-1 (PP-1) and PP-2A in the mechanism of Na+/K+-ATPase activation by insulin in the rat skeletal muscle cell line L6. |
| 419 | 9295306 | Immunoprecipitation of the enzyme from 32P-labeled cells with an antibody directed against the alpha-1 subunit of the enzyme revealed a 60% decrease in 110-kDa protein phosphorylation in insulin-treated cells. |
| 420 | 9295306 | To further confirm the role of PP-1, we used L6 cell lines that overexpress the glycogen/SR-associated regulatory subunit of PP-1, PP-1G. |
| 421 | 9295306 | Overexpression of PP-1G resulted in a 3-fold increase in insulin-stimulated PP-1 catalytic activity. |
| 422 | 9295306 | Inhibition of phosphatidylinositol-3 kinase with wortmannin blocked insulin-stimulated PP-1 activation as well as the dephosphorylation and activation of Na+/K+-ATPase. |
| 423 | 9295306 | We conclude that insulin regulates the activity of Na+/K+-ATPase by promoting dephosphorylation of the alpha subunit via an insulin-stimulated PP-1 and that phosphatidylinositol-3 kinase-generated signals may mediate insulin activation of PP-1 and Na+/K+-ATPase. |
| 424 | 9295306 | In this study, we examined the potential role of serine/threonine protein phosphatase-1 (PP-1) and PP-2A in the mechanism of Na+/K+-ATPase activation by insulin in the rat skeletal muscle cell line L6. |
| 425 | 9295306 | Immunoprecipitation of the enzyme from 32P-labeled cells with an antibody directed against the alpha-1 subunit of the enzyme revealed a 60% decrease in 110-kDa protein phosphorylation in insulin-treated cells. |
| 426 | 9295306 | To further confirm the role of PP-1, we used L6 cell lines that overexpress the glycogen/SR-associated regulatory subunit of PP-1, PP-1G. |
| 427 | 9295306 | Overexpression of PP-1G resulted in a 3-fold increase in insulin-stimulated PP-1 catalytic activity. |
| 428 | 9295306 | Inhibition of phosphatidylinositol-3 kinase with wortmannin blocked insulin-stimulated PP-1 activation as well as the dephosphorylation and activation of Na+/K+-ATPase. |
| 429 | 9295306 | We conclude that insulin regulates the activity of Na+/K+-ATPase by promoting dephosphorylation of the alpha subunit via an insulin-stimulated PP-1 and that phosphatidylinositol-3 kinase-generated signals may mediate insulin activation of PP-1 and Na+/K+-ATPase. |
| 430 | 9354853 | Changes in the signalling status of the small GTP-binding proteins Rac and Rho do not influence insulin-stimulated hexose transport. |
| 431 | 9354853 | Post-receptor signalling molecules that convey the signal from the activated insulin receptor to the actual process of Glut4 translocation and hexose uptake are poorly understood. |
| 432 | 9354853 | Various studies have suggested a requirement of the lipid kinase phosphatidylinositol-3 kinase (PI3-kinase) in this process. |
| 433 | 9354853 | PI3kinase regulates the activation status of the small GTP-binding protein Rac which, in turn, is able to activate another G-protein Rho. |
| 434 | 9354853 | Rac and Rho are known to regulate the structure of the membrane- and cytoplasmic actin-cytoskeleton. |
| 435 | 9354853 | We have examined whether Rac and Rho transfer the signals generated by PI3kinase towards insulin-stimulated hexose uptake. |
| 436 | 9354853 | We conclude that Rac and Rho are unlikely to be involved in insulin-stimulated hexose transport, suggesting a possible contribution of other signalling pathways, downstream of PI3kinase to this process. |
| 437 | 9356025 | Concomitant insulin stimulation (three- to six-fold [P < 0.05]) of thigh glucose clearance, muscle insulin receptor tyrosine kinase (IRTK), insulin receptor substrate-1 (IRS-1) tyrosine phosphorylation, and IRS-1-associated phosphatidylinositol 3-kinase (PI 3-kinase) was observed in the rested leg. |
| 438 | 9356025 | A twofold higher insulin-stimulated glucose clearance in the exercised compared with the rested thigh was accompanied by unaltered maximal IRTK activation and IRS-1 tyrosine phosphorylation, and by a decreased (approximately 50%, P < 0.05) maximal IRS-1 associated PI 3-kinase activation. |
| 439 | 9356025 | Prior exercise caused significantly faster insulin-stimulated tyrosine phosphorylation of IRS-1, PI 3-kinase activity, and glucose clearance compared with those in the rested thigh. |
| 440 | 9368055 | Insulin receptor substrate-2 (IRS-2) can mediate the action of insulin to stimulate translocation of GLUT4 to the cell surface in rat adipose cells. |
| 441 | 9368055 | Insulin receptor substrates-1 and -2 (IRS-1 and -2) are important substrates of the insulin receptor tyrosine kinase. |
| 442 | 9368055 | In the present study, we demonstrate that IRS-2 can mediate translocation of the insulin responsive glucose transporter GLUT4 in a physiologically relevant target cell for insulin action. |
| 443 | 9368055 | Co-immunoprecipitation experiments performed on cell lysates derived from freshly isolated rat adipose cells incubated in the presence or absence of insulin indicated that twice as much phosphatidylinositol 3-kinase was associated with endogenous IRS-1 as with IRS-2 after insulin stimulation. |
| 444 | 9368055 | When rat adipose cells in primary culture were transfected with expression vectors for IRS-1 or IRS-2, we observed 40-fold overexpression of human IRS-1 or murine IRS-2. |
| 445 | 9368055 | To examine the role of IRS-2 in insulin-stimulated translocation of GLUT4, we studied the effects of overexpression of IRS-1 and -2 on translocation of a co-transfected epitope-tagged GLUT4 (GLUT4-HA). |
| 446 | 9368055 | Overexpression of IRS-1 or IRS-2 in adipose cells resulted in a significant increase in the basal level of cell surface GLUT4 (in the absence of insulin). |
| 447 | 9368055 | Interestingly, at maximally effective concentrations of insulin (60 nM), the level of cell surface GLUT4 in cells overexpressing IRS-1 or -2 significantly exceeded the maximal recruitment observed in the control cells (160 and 135% of control, respectively; p < 0.003). |
| 448 | 9368055 | Our data directly demonstrate that IRS-2, like IRS-1, is capable of participating in insulin signal transduction pathways leading to the recruitment of GLUT4. |
| 449 | 9388271 | Activation of protein kinase C stimulates tyrosine phosphorylation and activation of ErbB2 and ErbB3. |
| 450 | 9388271 | Purification of the 190-kDa tyrosine-phosphorylated protein revealed that it consists of both ErbB2 and ErbB3. |
| 451 | 9388271 | Following PMA-induced tyrosine phosphorylation, ErbB2 and ErbB3 were able to associate with the SH2 domains of several signaling proteins including the p85alpha subunit of phosphatidylinositol 3-kinase, Syp, and Grb2. |
| 452 | 9388271 | Both ErbB2 and paxillin also exhibit reduced migration on SDS-polyacrylamide gel electrophoresis following PMA treatment, suggesting that they are also phosphorylated on serine/threonine residues. |
| 453 | 9388271 | The activation of ErbB2 and ErbB3 that is initiated by PMA may contribute to the tumor promoting activity of these compounds. |
| 454 | 9388272 | Comparison of phorbol ester and sphingomyelinase-induced phosphorylation of ErbB2 and ErbB3. |
| 455 | 9388272 | Chem. 272, 31172-31181), we demonstrated that phorbol 12-myristate 13-acetate (PMA) treatment of Fao cells induces tyrosine phosphorylation of several proteins including ErbB2 and ErbB3. |
| 456 | 9388272 | In the present study we show that sphingomyelinase also results in the enhanced tyrosine phosphorylation of ErbB2 and ErbB3 in these cells. |
| 457 | 9388272 | Prolonged insulin treatment resulted in decreased expression of both ErbB2 and ErbB3. |
| 458 | 9388272 | Insulin also appears to negatively regulate the protein tyrosine kinase responsible for phosphorylating ErbB2 in PMA-stimulated cells. |
| 459 | 9388272 | The former effect of insulin was relieved by treatment with inhibitors of phosphatidylinositol 3-kinase. |
| 460 | 9398740 | This observation led to the hypothesis that these amino acid substitutions may impair the function of IRS-1, thereby causing the insulin resistance seen in patients with NIDDM. |
| 461 | 9398740 | We constructed four IRS-1 expression vectors for transfection in COS-7 cells: wild-type, single mutant (Gly819-->Arg), double mutant (Gly819-->Arg; Gly972-->Arg), and triple mutant (Gly819-->Arg; Gly972-->Arg; Arg1221-->Cys) IRS-1. |
| 462 | 9398740 | The mutations did not alter the level of expression or the extent of insulin receptor-mediated tyrosine phosphorylation of recombinant IRS-1. |
| 463 | 9398740 | Moreover, the mutations did not lead to a detectable impairment in the association of recombinant IRS-1 with important downstream effectors, including the p85 subunit of phosphatidylinositol 3-kinase and growth factor receptor-binding protein-2. |
| 464 | 9399964 | Differential regulation of insulin receptor substrates-1 and -2 (IRS-1 and IRS-2) and phosphatidylinositol 3-kinase isoforms in liver and muscle of the obese diabetic (ob/ob) mouse. |
| 465 | 9399964 | In this study, we have evaluated the roles of IRS-1 and IRS-2 in signaling to the phosphatidylinositol (PI) 3-kinase pathway in the ob/ob mouse, a model of the insulin resistance of obesity and non-insulin-dependent diabetes mellitus. |
| 466 | 9399964 | We find that the levels of expression of both IRS-1 and IRS-2 are decreased approximately 50% in muscle, whereas in liver the decrease is significantly greater for IRS-2 (72%) than for IRS-1 (29%). |
| 467 | 9399964 | This results in differential decreases in IRS-1 and IRS-2 phosphorylation, docking of the p85alpha regulatory subunit of PI 3-kinase, and activation of this enzyme in these two insulin target tissues. |
| 468 | 9399964 | This resulted in a 45% decrease in the p85alpha form of PI 3-kinase, a ninefold increase in the AS53/p55alpha, and a twofold increase in p50alpha isoforms. |
| 469 | 9399964 | Thus, there are multiple alterations in the early steps of insulin signaling in the ob/ob mouse, with differential regulation of IRS-1 and IRS-2, various PI 3-kinase regulatory isoforms, and a lack of compensation for the decrease in insulin signaling by any of the known alternative pathways at these levels. |
| 470 | 9421369 | Altered expression levels and impaired steps in the pathway to phosphatidylinositol 3-kinase activation via insulin receptor substrates 1 and 2 in Zucker fatty rats. |
| 471 | 9421369 | To elucidate the mechanism of obesity-related insulin resistance, we investigated the impaired steps in the processes of phosphatidylinositol (PI) 3-kinase activation through binding with insulin receptor substrates 1 and 2 (IRS-1 and IRS-2) in liver and muscle of Zucker fatty rats. |
| 472 | 9421369 | The expressions of IRS-1 and IRS-2 were shown to be downregulated in both liver and muscle in fatty rats (hepatic IRS-1, 83%; hepatic IRS-2, 45%; muscle IRS-1, 60%; muscle IRS-2, 78%), resulting in decreased tyrosine phosphorylation in response to insulin stimulation. |
| 473 | 9421369 | Despite the decrease in the tyrosine phosphorylation levels of hepatic IRS-1 and IRS-2 being mild to moderate, associated PI 3-kinase activities were dramatically decreased in fatty rats (IRS-1, 14%; IRS-2, 10%), which may suggest alteration in the sites of phosphorylated tyrosine residues of hepatic IRS-1 and IRS-2. |
| 474 | 9421369 | In addition, we demonstrated that the expressions of p85alpha and p55alpha regulatory subunits of PI 3-kinase were reduced (p85alpha, 67%; p55alpha, 54%), and that the p50alpha regulatory subunit was markedly upregulated (176%) in the livers of fatty rats without apparent alterations in expressions of the catalytic subunits p110alpha and p110beta. |
| 475 | 9421369 | Altered expression levels and impaired steps in the pathway to phosphatidylinositol 3-kinase activation via insulin receptor substrates 1 and 2 in Zucker fatty rats. |
| 476 | 9421369 | To elucidate the mechanism of obesity-related insulin resistance, we investigated the impaired steps in the processes of phosphatidylinositol (PI) 3-kinase activation through binding with insulin receptor substrates 1 and 2 (IRS-1 and IRS-2) in liver and muscle of Zucker fatty rats. |
| 477 | 9421369 | The expressions of IRS-1 and IRS-2 were shown to be downregulated in both liver and muscle in fatty rats (hepatic IRS-1, 83%; hepatic IRS-2, 45%; muscle IRS-1, 60%; muscle IRS-2, 78%), resulting in decreased tyrosine phosphorylation in response to insulin stimulation. |
| 478 | 9421369 | Despite the decrease in the tyrosine phosphorylation levels of hepatic IRS-1 and IRS-2 being mild to moderate, associated PI 3-kinase activities were dramatically decreased in fatty rats (IRS-1, 14%; IRS-2, 10%), which may suggest alteration in the sites of phosphorylated tyrosine residues of hepatic IRS-1 and IRS-2. |
| 479 | 9421369 | In addition, we demonstrated that the expressions of p85alpha and p55alpha regulatory subunits of PI 3-kinase were reduced (p85alpha, 67%; p55alpha, 54%), and that the p50alpha regulatory subunit was markedly upregulated (176%) in the livers of fatty rats without apparent alterations in expressions of the catalytic subunits p110alpha and p110beta. |
| 480 | 9421381 | No difference in mRNA expression between omental and subcutaneous adipose tissue was observed for hormone sensitive lipase, lipoprotein lipase, 6-phosphofructo-1-kinase, insulin receptor substrate 1, p85alpha regulatory subunit of phosphatidylinositol-3-kinase, and Rad. |
| 481 | 9421381 | Perhaps consistent with a less efficient insulin signaling, a twofold reduction in GLUT4, glycogen synthase, and leptin mRNA expression was observed in omental adipose tissue. |
| 482 | 9422724 | To test this, binding studies were conducted with tandem domains from the five signaling enzymes: phosphatidylinositol 3-kinase p85, ZAP-70, Syk, SHP-2, and phospholipase C-gamma1. |
| 483 | 9422724 | Bisphosphorylated TAMs (tyrosine-based activation motifs) were derived from biologically relevant sites in platelet-derived growth factor, T cell, B cell, and high affinity IgE receptors and the receptor substrates IRS-1 (insulin receptor substrate-1) and SHPS-1/SIRP. |
| 484 | 9422753 | 14-3-3beta protein associates with insulin receptor substrate 1 and decreases insulin-stimulated phosphatidylinositol 3'-kinase activity in 3T3L1 adipocytes. |
| 485 | 9422753 | An in vitro binding study revealed that glutathione S-transferase-14-3-3beta fusion protein directly associates with recombinant IRS-1. |
| 486 | 9422753 | Pretreatment of recombinant IRS-1 with alkaline phosphatase clearly decreased this association. |
| 487 | 9422753 | When the cells are treated with insulin, phosphatidylinositol 3'-kinase (PI3K) is supposed to complex either 14-3-3beta-IRS-1 or IRS-1. |
| 488 | 9422753 | The specific activity of the PI3K in the former was approximately half of that in the latter, suggesting that 14-3-3beta protein bound to IRS-1 inhibits insulin-stimulated lipid kinase activity of PI3K in 3T3L1 adipocytes. |
| 489 | 9422753 | 14-3-3beta protein associates with insulin receptor substrate 1 and decreases insulin-stimulated phosphatidylinositol 3'-kinase activity in 3T3L1 adipocytes. |
| 490 | 9422753 | An in vitro binding study revealed that glutathione S-transferase-14-3-3beta fusion protein directly associates with recombinant IRS-1. |
| 491 | 9422753 | Pretreatment of recombinant IRS-1 with alkaline phosphatase clearly decreased this association. |
| 492 | 9422753 | When the cells are treated with insulin, phosphatidylinositol 3'-kinase (PI3K) is supposed to complex either 14-3-3beta-IRS-1 or IRS-1. |
| 493 | 9422753 | The specific activity of the PI3K in the former was approximately half of that in the latter, suggesting that 14-3-3beta protein bound to IRS-1 inhibits insulin-stimulated lipid kinase activity of PI3K in 3T3L1 adipocytes. |
| 494 | 9435517 | This effect of exercise is similar to the action of insulin on glucose uptake, and the mechanism through which both stimuli increase skeletal muscle glucose uptake involves the translocation of GLUT-4 glucose transporters to the plasma membrane and transverse tubules. |
| 495 | 9435517 | Most studies suggest that exercise and insulin recruit distinct GLUT-4-containing vesicles and/or mobilize different "pools" of GLUT-4 proteins originating from unique intracellular locations. |
| 496 | 9435517 | There are different intracellular signaling pathways that lead to insulin- and exercise-stimulated GLUT-4 translocation. |
| 497 | 9435517 | Insulin utilizes a phosphatidylinositol 3-kinase-dependent mechanism, whereas the exercise signal may be initiated by calcium release from the sarcoplasmic reticulum leading to the activation of other signaling intermediaries, and there is also evidence for autocrine- or paracrine-mediated activation of transport. |
| 498 | 9440478 | In adipocytes isolated from control rats, insulin (5 nmol/L) stimulated particulate serine/threonine protein phosphatase-1 (PP-1) activity (56% increase over the basal value after 5 minutes). |
| 499 | 9440478 | In contrast, adipocytes from diabetic GK rats exhibited a 32% decrease in basal (P < .05) and a 65% decrease in insulin-stimulated PP-1 activity compared with values in control Wistar rats. |
| 500 | 9440478 | Insulin treatment resulted in a 50% to 60% inhibition in PP-2A activity in control rats, but failed to inhibit PP-2A activity in diabetic GK rat adipocytes. |
| 501 | 9440478 | The defects in PP-1/PP-2A activation/inactivation were accompanied by inhibition of insulin's effect on mitogen-activated protein kinase (MAPK) activation. |
| 502 | 9440478 | In addition, insulin-stimulated tyrosine phosphorylation of insulin receptor (IR) substrate-1 (IRS-1) was decreased more than 90% compared with control values, while a twofold increase in basal IRS-1 phosphorylation status was observed in diabetic GK rats. |
| 503 | 9440478 | The abnormalities in IRS-1 phosphorylation were accompanied by a severe impairment of insulin-mediated targeting of the Grb2/Sos complex to the plasma membrane. |
| 504 | 9440478 | We conclude that (1) a rapid activation of PP-1 along with concomitant inhibition of cytosolic PP-2A may be important in the mechanism of insulin action in a normal cell, and (2) the resistance to insulin in terms of glucose uptake and glycogen synthesis observed in diabetic GK rats is partly due to defective regulation of PP-1, PP-2A, and MAPK caused by multiple defects in the upstream insulin signaling components (IRS-1/phosphatidylinositol-3-kinase [PI3-kinase] and Grb2/Sos) that participate in insulin-mediated activation of PP-1 and inactivation of PP-2A. |
| 505 | 9461521 | A novel phosphoinositolglycan-peptide (PIG-P) from the yeast Saccharomyces cerevisiae potently mimicks insulin action on glucose transport and metabolism in rat muscle and adipose tissue. |
| 506 | 9461521 | Rapid onset and reversibility of PIG-P action on glucose transport were observed in isolated adipocytes with a half-time of transport stimulation of 6-8 min (insulin less than 5 min). |
| 507 | 9461521 | Combined treatment with PIG-P and insulin indicated additive stimulation of glucose transport at submaximal concentrations and non-additive action of both agents at maximal doses. |
| 508 | 9461521 | The tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1) was markedly increased in response to PIG-P in rat cardiomyocytes without any effect on the tyrosine phosphorylation of the insulin receptor beta-subunit. |
| 509 | 9461521 | Downstream signalling of IRS-1 was then analysed by monitoring IRS-1-associated phosphatidylinositol 3-kinase (PI 3-kinase) activity in cardiomyocytes. |
| 510 | 9461521 | A stable (2 and 15 min incubation with PIG-P) 7-fold stimulation corresponding to about 50% of insulin action could be detected. |
| 511 | 9461521 | Increased tyrosine phosphorylation of IRS-1 and enhanced PI 3-kinase activity in response to PIG-P independent of the insulin receptor was also observed in isolated adipocytes. |
| 512 | 9461521 | These data suggest divergent upstream signalling by insulin and PIG-P involving phosphoproteins not affected by insulin. |
| 513 | 9461521 | However, PIG-P and insulin action converge at the level of IRS-1 inducing insulin-independent PI 3-kinase-mediated signalling to glucose transport. |
| 514 | 9468278 | Insulin-stimulated chemokinesis in normal human neutrophils is dependent on D-glucose concentration and sensitive to inhibitors of tyrosine kinase and phosphatidylinositol 3-kinase. |
| 515 | 9468278 | The tyrosine kinase inhibitor, genistein, or the phosphatidylinositol 3-kinase inhibitor, wortmannin, abolished the chemokinetic effect of 160 microU/mL insulin in the presence of 5 mM D-glucose. |
| 516 | 9468278 | This indicates that the insulin effect on locomotion is indeed mediated by receptor-associated tyrosine kinase activation and involving phosphatidylinositol 3-kinase. |
| 517 | 9468278 | Insulin-stimulated chemokinesis in normal human neutrophils is dependent on D-glucose concentration and sensitive to inhibitors of tyrosine kinase and phosphatidylinositol 3-kinase. |
| 518 | 9468278 | The tyrosine kinase inhibitor, genistein, or the phosphatidylinositol 3-kinase inhibitor, wortmannin, abolished the chemokinetic effect of 160 microU/mL insulin in the presence of 5 mM D-glucose. |
| 519 | 9468278 | This indicates that the insulin effect on locomotion is indeed mediated by receptor-associated tyrosine kinase activation and involving phosphatidylinositol 3-kinase. |
| 520 | 9468278 | Insulin-stimulated chemokinesis in normal human neutrophils is dependent on D-glucose concentration and sensitive to inhibitors of tyrosine kinase and phosphatidylinositol 3-kinase. |
| 521 | 9468278 | The tyrosine kinase inhibitor, genistein, or the phosphatidylinositol 3-kinase inhibitor, wortmannin, abolished the chemokinetic effect of 160 microU/mL insulin in the presence of 5 mM D-glucose. |
| 522 | 9468278 | This indicates that the insulin effect on locomotion is indeed mediated by receptor-associated tyrosine kinase activation and involving phosphatidylinositol 3-kinase. |
| 523 | 9496228 | Insulin-specific binding and 95 kDa autophosphorylation of insulin receptor in OLETF rats were not different from those in LETO rats. |
| 524 | 9496228 | Insulin-induced diacylglycerol (DG) production and Mono Q column-purified protein kinase C (PKC) translocation in adipocytes of OLETF rats were decreased compared with those of LETO rats. |
| 525 | 9496228 | Insulin-induced PKC beta translocation from cytosol to membrane was also decreased in adipocytes of OLETF rats. |
| 526 | 9496228 | Analysis of mRNA levels of PKC isoforms in adipocytes of OLETF rats showed decreases of basal level and insulin-induced delayed responses of PKC beta I, beta II, epsilon and zeta mRNA in OLETF rats. |
| 527 | 9496228 | On the other hand, insulin- or phorbol ester-induced phosphatidylinositol 3-kinase (PI 3-kinase) activation was decreased in adipocytes of OLETF rats compared with those of LETO rats. |
| 528 | 9518707 | The effect of insulin was not blocked by wortmannin, an inhibitor of phosphatidylinositol 3-kinase. |
| 529 | 9519710 | Possibility of distinct insulin-signaling pathways beyond phosphatidylinositol 3-kinase-mediating glucose transport and lipogenesis. |
| 530 | 9519710 | Tyrosine phosphorylation of the insulin receptor (IR), insulin receptor substrates 1 and 2 (IRS-1 and IRS-2), and pp60, and phosphatidylinositol (PI) 3-kinase activity (using PI as substrate) and mitogen-activated protein kinase (MAPK) activity were assayed in cell lysates. |
| 531 | 9519710 | Englitazone did not increase IR, IRS-1/IRS-2, pp60, or MAPK phosphorylation, nor did it enhance insulin's stimulation of these parameters. |
| 532 | 9519710 | Significant (63%) inhibition of insulin-stimulated lipogenesis occurred at a concentration of englitazone (30 micromol/l) that did not affect MAPK activation, which suggests that the drug's inhibitory effect on lipogenesis is not mediated by this pathway. |
| 533 | 9525995 | Exposure of cells to high physiologic concentrations of amino acids activates intermediates important in the initiation of protein synthesis, including p70 S6 kinase and PHAS-I, in synergy with insulin. |
| 534 | 9525995 | Concurrently, amino acids inhibit early steps in insulin action critical for glucose transport and inhibition of gluconeogenesis, including decreased insulin-stimulated tyrosine phosphorylation of IRS-1 and IRS-2, decreased binding of grb 2 and the p85 subunit of phosphatidylinositol 3-kinase to IRS-1 and IRS-2, and a marked inhibition of insulin-stimulated phosphatidylinositol 3-kinase. |
| 535 | 9563515 | Evidence against protein kinase B as a mediator of contraction-induced glucose transport and GLUT4 translocation in rat skeletal muscle. |
| 536 | 9563515 | However, contraction stimulation does not involve the insulin signalling intermediate phosphatidylinositol 3-kinase (PI 3-kinase). |
| 537 | 9563515 | Protein kinase B (PKB) has recently been identified as a direct downstream target of PI 3-kinase in the insulin signalling pathway. |
| 538 | 9563515 | Insulin stimulates both glucose transport, GLUT4 cell-surface content and PKB activity (by 4-6-fold above basal) in a wortmannin-sensitive manner in in vitro incubated rat soleus muscles. |
| 539 | 9563515 | By contrast, muscle contraction, which stimulates glucose transport and the cell surface content of GLUT4 by 3-fold above basal levels, had no effect on PKB activity. |
| 540 | 9563515 | These data demonstrate that PKB is not a mediator of contraction-induced glucose transport and GLUT4 translocation. |
| 541 | 9565570 | Differential compartmentalization and trafficking of insulin receptor substrate (IRS)-1 and IRS-2. |
| 542 | 9565570 | We find that insulin receptor substrate (IRS)-1 is 2-fold more concentrated in the intracellular membrane (IM) compartment than in cytosol, whereas IRS-2 is 2-fold more concentrated in cytosol than in IM. |
| 543 | 9565570 | Insulin stimulation induces rapid tyrosine phosphorylation of both IRS-1 and IRS-2. |
| 544 | 9565570 | Furthermore, after insulin stimulation, both IRS-1 and IRS-2 translocate from IM to cytosol with a t1/2 of 3.5 min. |
| 545 | 9565570 | By comparison, within 1 min after insulin stimulation, 40% of the total pool of the 85-kDa subunit of phosphatidylinositol 3-kinase (p85) is recruited from cytosol to IM, the greater part of which can be accounted for by binding to IRS-1 present in the IM. |
| 546 | 9565570 | The p85 binding and phosphatidylinositol 3-kinase activity associated with IRS-2 rapidly decrease in both IM and cytosol, whereas those associated with IRS-1 stay at a relatively high level in IM and increase with time in cytosol despite a return of p85 to the cytosol and decreasing tyrosine phosphorylation of cytosolic IRS-1. |
| 547 | 9565570 | These data indicate that IRS-1 and IRS-2 are differentially distributed in the cell and move from IM to cytosol following insulin stimulation. |
| 548 | 9565570 | Insulin-stimulated IRS-1 and IRS-2 signaling occurs mainly in the IM and shows different kinetics; IRS-1-mediated signaling is more stable, whereas IRS-2-mediated signaling is more transient. |
| 549 | 9565570 | Differential compartmentalization and trafficking of insulin receptor substrate (IRS)-1 and IRS-2. |
| 550 | 9565570 | We find that insulin receptor substrate (IRS)-1 is 2-fold more concentrated in the intracellular membrane (IM) compartment than in cytosol, whereas IRS-2 is 2-fold more concentrated in cytosol than in IM. |
| 551 | 9565570 | Insulin stimulation induces rapid tyrosine phosphorylation of both IRS-1 and IRS-2. |
| 552 | 9565570 | Furthermore, after insulin stimulation, both IRS-1 and IRS-2 translocate from IM to cytosol with a t1/2 of 3.5 min. |
| 553 | 9565570 | By comparison, within 1 min after insulin stimulation, 40% of the total pool of the 85-kDa subunit of phosphatidylinositol 3-kinase (p85) is recruited from cytosol to IM, the greater part of which can be accounted for by binding to IRS-1 present in the IM. |
| 554 | 9565570 | The p85 binding and phosphatidylinositol 3-kinase activity associated with IRS-2 rapidly decrease in both IM and cytosol, whereas those associated with IRS-1 stay at a relatively high level in IM and increase with time in cytosol despite a return of p85 to the cytosol and decreasing tyrosine phosphorylation of cytosolic IRS-1. |
| 555 | 9565570 | These data indicate that IRS-1 and IRS-2 are differentially distributed in the cell and move from IM to cytosol following insulin stimulation. |
| 556 | 9565570 | Insulin-stimulated IRS-1 and IRS-2 signaling occurs mainly in the IM and shows different kinetics; IRS-1-mediated signaling is more stable, whereas IRS-2-mediated signaling is more transient. |
| 557 | 9568686 | Bradykinin directly triggers GLUT4 translocation via an insulin-independent pathway. |
| 558 | 9568686 | Physical exercise induces translocation of GLUT4 from an intracellular pool to the cell surface in skeletal muscles and increases glucose uptake via an insulin-independent pathway. |
| 559 | 9568686 | To determine whether bradykinin directly triggers GLUT4 translocation, we established L6 myotubes, 3T3-L1 adipocytes, and Chinese hamster ovary cells stably expressing c-myc epitope-tagged GLUT4 (GLUT4myc) and bradykinin B2 receptors. |
| 560 | 9568686 | The signaling pathway does not seem to be mediated by Gi, phosphatidylinositol 3-kinase, or protein kinase C. |
| 561 | 9578588 | Vanadyl sulfate-stimulated glycogen synthesis is associated with activation of phosphatidylinositol 3-kinase and is independent of insulin receptor tyrosine phosphorylation. |
| 562 | 9578588 | We have shown earlier that different vanadium salts stimulate the MAP kinase pathway and ribosomal-S-6-kinase (p70s6k) in chinese hamster ovary cells overexpressing human insulin receptor (CHO-HIR cells) [Pandey, S. |
| 563 | 9578588 | In the present studies, we have investigated if similar to insulin, VS also activates phosphatidylinositol 3-kinase (PI3-k) activity, and whether VS-induced activation of the PI3-k, MAP kinase, and p70s6k pathways contributes to glycogen synthesis. |
| 564 | 9578588 | On the other hand, PD98059 and rapamycin, specific inhibitors of the MAP kinase pathway and p70s6k, respectively, were unable to inhibit VS-stimulated glycogen synthesis. |
| 565 | 9578588 | Moreover, VS-stimulated glycogen synthesis and PI3-k were observed without any change in the tyrosine phosphorylation of insulin receptor (IR) beta-subunit but were associated with increased tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1). |
| 566 | 9578588 | In addition, PI3-k activation was detected in IRS-1 immunoprecipitates from VS-stimulated cells, indicating that tyrosine-phosphorylated IRS-1 was able to interact and thereby activate PI3-k in response to VS. |
| 567 | 9578588 | Taken together, these results provide evidence that tyrosine phosphorylation of IRS-1 and activation of PI3-k play a key role in mediating the insulinomimetic effect of VS on glycogen synthesis independent of IR-tyrosine phosphorylation. |
| 568 | 9578588 | Vanadyl sulfate-stimulated glycogen synthesis is associated with activation of phosphatidylinositol 3-kinase and is independent of insulin receptor tyrosine phosphorylation. |
| 569 | 9578588 | We have shown earlier that different vanadium salts stimulate the MAP kinase pathway and ribosomal-S-6-kinase (p70s6k) in chinese hamster ovary cells overexpressing human insulin receptor (CHO-HIR cells) [Pandey, S. |
| 570 | 9578588 | In the present studies, we have investigated if similar to insulin, VS also activates phosphatidylinositol 3-kinase (PI3-k) activity, and whether VS-induced activation of the PI3-k, MAP kinase, and p70s6k pathways contributes to glycogen synthesis. |
| 571 | 9578588 | On the other hand, PD98059 and rapamycin, specific inhibitors of the MAP kinase pathway and p70s6k, respectively, were unable to inhibit VS-stimulated glycogen synthesis. |
| 572 | 9578588 | Moreover, VS-stimulated glycogen synthesis and PI3-k were observed without any change in the tyrosine phosphorylation of insulin receptor (IR) beta-subunit but were associated with increased tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1). |
| 573 | 9578588 | In addition, PI3-k activation was detected in IRS-1 immunoprecipitates from VS-stimulated cells, indicating that tyrosine-phosphorylated IRS-1 was able to interact and thereby activate PI3-k in response to VS. |
| 574 | 9578588 | Taken together, these results provide evidence that tyrosine phosphorylation of IRS-1 and activation of PI3-k play a key role in mediating the insulinomimetic effect of VS on glycogen synthesis independent of IR-tyrosine phosphorylation. |
| 575 | 9578588 | Vanadyl sulfate-stimulated glycogen synthesis is associated with activation of phosphatidylinositol 3-kinase and is independent of insulin receptor tyrosine phosphorylation. |
| 576 | 9578588 | We have shown earlier that different vanadium salts stimulate the MAP kinase pathway and ribosomal-S-6-kinase (p70s6k) in chinese hamster ovary cells overexpressing human insulin receptor (CHO-HIR cells) [Pandey, S. |
| 577 | 9578588 | In the present studies, we have investigated if similar to insulin, VS also activates phosphatidylinositol 3-kinase (PI3-k) activity, and whether VS-induced activation of the PI3-k, MAP kinase, and p70s6k pathways contributes to glycogen synthesis. |
| 578 | 9578588 | On the other hand, PD98059 and rapamycin, specific inhibitors of the MAP kinase pathway and p70s6k, respectively, were unable to inhibit VS-stimulated glycogen synthesis. |
| 579 | 9578588 | Moreover, VS-stimulated glycogen synthesis and PI3-k were observed without any change in the tyrosine phosphorylation of insulin receptor (IR) beta-subunit but were associated with increased tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1). |
| 580 | 9578588 | In addition, PI3-k activation was detected in IRS-1 immunoprecipitates from VS-stimulated cells, indicating that tyrosine-phosphorylated IRS-1 was able to interact and thereby activate PI3-k in response to VS. |
| 581 | 9578588 | Taken together, these results provide evidence that tyrosine phosphorylation of IRS-1 and activation of PI3-k play a key role in mediating the insulinomimetic effect of VS on glycogen synthesis independent of IR-tyrosine phosphorylation. |
| 582 | 9578588 | Vanadyl sulfate-stimulated glycogen synthesis is associated with activation of phosphatidylinositol 3-kinase and is independent of insulin receptor tyrosine phosphorylation. |
| 583 | 9578588 | We have shown earlier that different vanadium salts stimulate the MAP kinase pathway and ribosomal-S-6-kinase (p70s6k) in chinese hamster ovary cells overexpressing human insulin receptor (CHO-HIR cells) [Pandey, S. |
| 584 | 9578588 | In the present studies, we have investigated if similar to insulin, VS also activates phosphatidylinositol 3-kinase (PI3-k) activity, and whether VS-induced activation of the PI3-k, MAP kinase, and p70s6k pathways contributes to glycogen synthesis. |
| 585 | 9578588 | On the other hand, PD98059 and rapamycin, specific inhibitors of the MAP kinase pathway and p70s6k, respectively, were unable to inhibit VS-stimulated glycogen synthesis. |
| 586 | 9578588 | Moreover, VS-stimulated glycogen synthesis and PI3-k were observed without any change in the tyrosine phosphorylation of insulin receptor (IR) beta-subunit but were associated with increased tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1). |
| 587 | 9578588 | In addition, PI3-k activation was detected in IRS-1 immunoprecipitates from VS-stimulated cells, indicating that tyrosine-phosphorylated IRS-1 was able to interact and thereby activate PI3-k in response to VS. |
| 588 | 9578588 | Taken together, these results provide evidence that tyrosine phosphorylation of IRS-1 and activation of PI3-k play a key role in mediating the insulinomimetic effect of VS on glycogen synthesis independent of IR-tyrosine phosphorylation. |
| 589 | 9578588 | Vanadyl sulfate-stimulated glycogen synthesis is associated with activation of phosphatidylinositol 3-kinase and is independent of insulin receptor tyrosine phosphorylation. |
| 590 | 9578588 | We have shown earlier that different vanadium salts stimulate the MAP kinase pathway and ribosomal-S-6-kinase (p70s6k) in chinese hamster ovary cells overexpressing human insulin receptor (CHO-HIR cells) [Pandey, S. |
| 591 | 9578588 | In the present studies, we have investigated if similar to insulin, VS also activates phosphatidylinositol 3-kinase (PI3-k) activity, and whether VS-induced activation of the PI3-k, MAP kinase, and p70s6k pathways contributes to glycogen synthesis. |
| 592 | 9578588 | On the other hand, PD98059 and rapamycin, specific inhibitors of the MAP kinase pathway and p70s6k, respectively, were unable to inhibit VS-stimulated glycogen synthesis. |
| 593 | 9578588 | Moreover, VS-stimulated glycogen synthesis and PI3-k were observed without any change in the tyrosine phosphorylation of insulin receptor (IR) beta-subunit but were associated with increased tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1). |
| 594 | 9578588 | In addition, PI3-k activation was detected in IRS-1 immunoprecipitates from VS-stimulated cells, indicating that tyrosine-phosphorylated IRS-1 was able to interact and thereby activate PI3-k in response to VS. |
| 595 | 9578588 | Taken together, these results provide evidence that tyrosine phosphorylation of IRS-1 and activation of PI3-k play a key role in mediating the insulinomimetic effect of VS on glycogen synthesis independent of IR-tyrosine phosphorylation. |
| 596 | 9588442 | Short-term exposure to tumor necrosis factor-alpha does not affect insulin-stimulated glucose uptake in skeletal muscle. |
| 597 | 9588442 | It has been hypothesized that increased production of tumor necrosis factor-alpha (TNF-alpha) plays a role in causing the insulin resistance associated with obesity. |
| 598 | 9588442 | Obesity with insulin resistance is associated with increased production of TNF-alpha by fat cells. |
| 599 | 9588442 | Exposure of 3T3-L1 adipocytes to TNF-alpha for 3-4 days makes them insulin resistant. |
| 600 | 9588442 | TNF-alpha has also been reported to rapidly (15-60 min) cause insulin resistance, with a decrease in insulin-stimulated tyrosine phosphorylation, in a number of cultured cell lines. |
| 601 | 9588442 | Because skeletal muscle is the major tissue responsible for insulin-stimulated glucose disposal, we performed the present study to determine if acute exposure to TNF-alpha causes insulin resistance in muscle. |
| 602 | 9588442 | We found that exposure of soleus muscles to 6 nmol/l TNF-alpha for 45 min in vitro had no inhibitory effect on insulin-stimulated tyrosine phosphorylation of the insulin receptor or insulin receptor substrate 1 (IRS-1) or on phosphatidylinositol 3-kinase association with IRS-1. |
| 603 | 9588442 | Incubation of epitrochlearis and soleus muscles with 6 nmol/l TNF-alpha for 45 min or 4 h had no effect on insulin-stimulated 2-deoxyglucose (2-DG) uptake. |
| 604 | 9588442 | Treatment of epitrochlearis muscles with 2 nmol/l TNF-alpha for 8 h also had no effect on insulin-stimulated 2-DG uptake. |
| 605 | 9588442 | We conclude that in contrast to Fao hepatoma cells and 3T3-L1 fibroblasts, skeletal muscle does not become insulin resistant in response to short-term exposure to TNF-alpha. |
| 606 | 9604878 | Variant in the regulatory subunit of phosphatidylinositol 3-kinase (p85alpha): preliminary evidence indicates a potential role of this variant in the acute insulin response and type 2 diabetes in Pima women. |
| 607 | 9609121 | Evidence for and against a role for the phosphatidylinositol-3-kinase and mitogen activated protein kinase arms of the insulin-stimulated intracellular signalling networks is suggested. |
| 608 | 9648821 | Phosphatidylinositol 3-kinase (PI 3-kinase) has been implicated in the regulation of numerous cellular processes, including the insulin-induced regulation of glycogen synthase kinase 3 (GSK-3) and glucose transport. |
| 609 | 9648821 | The hormonal-induced inactivation of GSK-3 is mediated by protein kinase B (PKB), a downstream target of PI 3-kinase, whose involvement in other insulin-stimulated responses remains poorly defined at present. |
| 610 | 9648821 | Both wtPKBalpha and mPKBalpha expression led to a significant increase in the basal uptake of glucose and methyl-aminoisobutyric acid (a substrate for the system A amino acid transporter), at least to a level seen in control cells treated with insulin. |
| 611 | 9648821 | In the absence of insulin, only muscle cells expressing the constitutively active PKBalpha showed a significant increase in protein synthesis and an inhibition in GSK-3. |
| 612 | 9648821 | These observations imply that PKBalpha may have a role in the insulin-regulated control of these processes in skeletal muscle. |
| 613 | 9688833 | In this study, we examined the contribution of MAPK pathway in insulin-stimulated mitogenesis using primary vascular smooth muscle cells (VSMCs) isolated from aortas of normotensive Wistar-Kyoto rats (WKY) and spontaneous hypertensive rats (SHR). |
| 614 | 9688833 | VSMCs were grown to confluence in culture, serum starved, and examined for DNA synthesis (using [3H]thymidine (TDR), immunoprecipitated MAPK activity, and MAPK phosphatase (MKP-1) induction). |
| 615 | 9688833 | Pretreatment with insulin-like growth factor I (IGF-I) receptor antibody did not abolish mitogenesis mediated by 10-100 nM insulin, suggesting that insulin effect is mediated via its own receptors. |
| 616 | 9688833 | Insulin-stimulated mitogenesis was accompanied by a dose-dependent increase in MAPK activity in SHR, with a peak activation (>2-fold over basal) between 5 and 10 min with 100 nM insulin. |
| 617 | 9688833 | Insulin had very small effects on MAPK activity in WKY. |
| 618 | 9688833 | Pretreatment with MEK inhibitor, PD-98059, completely blocked insulin's effect on MAPK activation and mitogenesis. |
| 619 | 9688833 | Inhibition of phosphatidylinositol 3-kinase with wortmannin also prevented insulin's effects on MAPK activation and mitogenesis. |
| 620 | 9688833 | In WKY, insulin and IGF-I treatment resulted in a rapid induction of MKP-1, the dual-specificity MAPK phosphatase. |
| 621 | 9688833 | We conclude that insulin is mitogenic in SHR, and the effect appears to be mediated by sustained MAPK activation due to impaired insulin-mediated MKP-1 mRNA expression, which may act as an inhibitory feedback loop in attenuating MAPK signaling. |
| 622 | 9703344 | This hypothesis was based on recent studies showing the following: 1) muscle contraction increases AMPK activity and 2) perfusion of rat hindlimb skeletal muscles with 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR), a compound that results in increased AMPK activity, increased insulin-stimulated glucose uptake. |
| 623 | 9703344 | In the current study, isolated rat epitrochlearis muscles were treated to contract in vitro (via electrical stimulation for 10 min) and/or incubated in the absence or presence of AICAR (2 mmol/l), insulin (1 micromol/l), or wortmannin (100 nmol/l). |
| 624 | 9703344 | Both contraction and AICAR significantly increased AMPK activity, while the enzyme was not activated by insulin. |
| 625 | 9703344 | AICAR, contraction, and insulin all increased 3-O-methylglucose (3MG) transport by threefold to fivefold above basal. |
| 626 | 9703344 | The phosphatidylinositol 3-kinase (PI 3-kinase) inhibitor wortmannin completely blocked insulin-stimulated transport, but did not inhibit AICAR- or contraction-stimulated transport. |
| 627 | 9703344 | The increase in glucose transport with the combination of maximal AICAR plus maximal insulin treatments was partially additive, suggesting that these stimuli increase glucose transport by different mechanisms. |
| 628 | 9703344 | These data suggest that AICAR and contraction stimulate glucose transport by a similar insulin-independent signaling mechanism and are consistent with the hypothesis that AMPK is involved in exercise-stimulated glucose uptake. |
| 629 | 9737976 | Regulation of mitogen-activated protein kinase phosphatase-1 induction by insulin in vascular smooth muscle cells. |
| 630 | 9737976 | In this study, we examined the regulation of mitogen-activated protein kinase phosphatase (MKP-1) expression by insulin in primary vascular smooth muscle cell cultures. |
| 631 | 9737976 | Insulin caused a rapid time- and dose-dependent induction of MKP-1 mRNA and protein expression. |
| 632 | 9737976 | Blockade of nitric-oxide synthase (NOS) with NG-monomethyl-L-arginine acetate, and cGMP with RpcGMP, completely inhibited MKP-1 expression. |
| 633 | 9737976 | Insulin-mediated MKP-1 expression was preceded by inducible NOS (iNOS) induction and cGMP production. |
| 634 | 9737976 | Blockade of phosphatidylinositol 3-kinase (PI3-kinase) signaling with wortmannin inhibited insulin-mediated iNOS protein induction, cGMP production, and MKP-1 expression. |
| 635 | 9737976 | To evaluate potential interactions between NOS and the mitogen-activated protein kinase (MAPK) signaling pathways, we employed PD98059 and SB203580, two specific inhibitors of ERKs and p38 MAPK. |
| 636 | 9737976 | These inhibitors abolished the effect of insulin on MKP-1 expression. |
| 637 | 9737976 | Only PD98059 inhibited insulin-mediated iNOS protein induction. |
| 638 | 9737976 | Vascular smooth muscle cells from spontaneous hypertensive rats exhibited a marked decrease in MKP-1 induction due to defects in insulin-induced iNOS expression because of reductions in PI3-kinase activity. |
| 639 | 9737976 | We conclude that insulin-induced MKP-1 expression is mediated by PI3-kinase-initiated signals, leading to the induction of iNOS and elevated cGMP levels that stimulates MKP-1 expression. |
| 640 | 9792535 | Tyrosine phosphatase inhibitors, vanadate and pervanadate, stimulate glucose transport and GLUT translocation in muscle cells by a mechanism independent of phosphatidylinositol 3-kinase and protein kinase C. |
| 641 | 9792535 | Vanadate and pervanadate (pV) are protein tyrosine phosphatase (PTP) inhibitors that mimic insulin to stimulate glucose transport. |
| 642 | 9792535 | Vanadate and pV stimulated the translocation of GLUTs from an intracellular compartment to the plasma membrane; this stimulation was not blocked by wortmannin, but insulin-induced GLUT translocation was inhibited. |
| 643 | 9792535 | Similar results were obtained in cultured H9c2 cardiac muscle cells in which wortmannin did not inhibit glucose transport or the vanadate-induced translocation of GLUT4 in c-myc-GLUT4 transfected cells. |
| 644 | 9792535 | The ser/thr kinase PKB (Akt/PKB/RAC-PK) is activated by insulin, lies downstream of PI 3-kinase, and has been implicated in signaling of glucose transport. |
| 645 | 9792535 | Insulin and pV stimulated PKB activity, and both were inhibited by wortmannin. |
| 646 | 9829964 | CREB is a regulatory target for the protein kinase Akt/PKB. |
| 647 | 9829964 | The nuclear factor CREB stimulates the expression of cellular genes following its protein kinase A-mediated phosphorylation at Ser-133. |
| 648 | 9829964 | Recent studies showing that CREB and its paralog CREM are required for survival of certain cell types prompted us to examine whether CREB is a nuclear target for activation via the growth factor-dependent Ser/Thr kinase Akt/PKB. |
| 649 | 9829964 | When overexpressed in serum-stimulated cells, Akt/PKB potently induced Ser-133 phosphorylation of CREB and promoted recruitment of CBP. |
| 650 | 9829964 | Correspondingly, Akt/PKB stimulated target gene expression via CREB in a phospho(Ser-133)-dependent manner. |
| 651 | 9829964 | Akt/PKB induced CREB activity only in response to serum stimulation, and this effect was suppressed by the phosphatidylinositol 3-kinase inhibitor LY 294002. |
| 652 | 9829964 | Our results support the notion that Akt/PKB promotes cell survival, at least in part, by stimulating the expression of cellular genes via the CREB/CBP nuclear transduction pathway. |
| 653 | 9830057 | Insulin stimulates sequestration of beta-adrenergic receptors and enhanced association of beta-adrenergic receptors with Grb2 via tyrosine 350. |
| 654 | 9830057 | Both insulin and insulin-like growth factor-1 stimulate internalization of beta-adrenergic receptors, contributing to the counter-regulatory effects of these growth factors on catecholamine action. |
| 655 | 9830057 | Insulin administration in vitro and in vivo stimulates phosphorylation of Tyr-350 of the beta-adrenergic receptor, creating an Src homology 2 domain available for binding of the adaptor molecule Grb2. |
| 656 | 9830057 | The association of Grb2 with beta-adrenergic receptors was established using antibodies to Grb2 as well as a Grb2-glutathione S-transferase fusion protein. |
| 657 | 9830057 | Insulin treatment of cells provokes binding of Grb2 to beta2-adrenergic receptors. |
| 658 | 9830057 | Insulin also stimulates association of phosphatidylinositol 3-kinase and dynamin, via the Src homology 3 domain of Grb2. |
| 659 | 9830057 | The Tyr-350 --> Phe mutant form of the beta2-adrenergic receptor, lacking the site for tyrosine phosphorylation, fails to bind Grb2 in response to insulin, fails to display internalization of beta2-adrenergic receptor in response to insulin, and is no longer subject to the counter-regulatory effects of insulin on cyclic AMP accumulation. |
| 660 | 9854185 | In the present study, we have investigated the diabetes-associated alterations in the insulin signalling cascade, especially the phosphatidylinositol-3 kinase (PI-3 kinase)/p70 S6 kinase (p70(S6K)) pathway, in rat skeletal muscle. |
| 661 | 9854185 | LY 294002, a specific inhibitor of PI-3 kinase, markedly decreased the basal rate of protein synthesis and completely prevented insulin-mediated stimulation of this process both in control and diabetic rats. |
| 662 | 9854185 | Thus, PI-3 kinase is required for insulin-stimulated muscle protein synthesis in diabetic rats as in the controls. |
| 663 | 9854185 | Neither basal nor insulin-stimulated p70(S6K) activity, a signalling element lying downstream of mTOR, were modified by STZ-diabetes. |
| 664 | 9886967 | DHEA improves glucose uptake via activations of protein kinase C and phosphatidylinositol 3-kinase. |
| 665 | 9886967 | Pretreatment with DHEA increased insulin-induced 2-[3H]DG uptake without alterations of insulin specific binding and autophosphorylation of insulin receptor. |
| 666 | 9892238 | Enhanced insulin-stimulated activation of phosphatidylinositol 3-kinase in the liver of high-fat-fed rats. |
| 667 | 9892238 | Insulin receptor substrate (IRS)-1 and IRS-2, which mediate phosphatidylinositol (PI) 3-kinase activation, play essential roles in insulin-induced translocation of GLUT4 and in glycogen synthesis. |
| 668 | 9892238 | In this study, we investigated the process of PI 3-kinase activation via binding with IRS-1 and -2 in liver, muscle, and fat of high-fat-fed rats, a model of insulin-resistant diabetes. |
| 669 | 9892238 | In the liver of high-fat-fed rats, insulin increased the PI 3-kinase regulatory subunit p85alpha and the PI 3-kinase activities associated with IRS-1 3.6- and 2.4-fold, and with IRS-2, 4.7- and 3.0-fold, respectively, compared with those in control rats. |
| 670 | 9892238 | The tyrosine phosphorylation levels of IRS-1 and IRS-2 were not significantly altered, however. |
| 671 | 9892238 | Taking into consideration that hepatic PI 3-kinase activation is severely impaired in obese diabetic models such as Zucker fatty rats, it is possible that the mechanism by which a high-fat diet causes insulin resistance is quite different from that associated with obesity and overeating due to abnormality in the leptin system. |
| 672 | 9988280 | Increased insulin sensitivity and hypoglycaemia in mice lacking the p85 alpha subunit of phosphoinositide 3-kinase. |
| 673 | 9988280 | Although a role for phosphoinositide-3-kinase (PI3K) activity in insulin-stimulated glucose transport and glucose transporter isoform 4 (Glut4) translocation has been suggested in vitro, its role in vivo and the molecular link between activation of PI3K and translocation has not yet been elucidated. |
| 674 | 9988280 | To determine the role of PI3K in glucose homeostasis, we generated mice with a targeted disruption of the gene encoding the p85alpha regulatory subunit of PI3K (Pik3r1; refs 3-5). |
| 675 | 9988280 | Insulin-stimulated PI3K activity associated with insulin receptor substrates (IRSs) was mediated via full-length p85 alpha in wild-type mice, but via the p50 alpha alternative splicing isoform of the same gene in Pik3r1-/- mice. |
| 676 | 9988280 | This isoform switch was associated with an increase in insulin-induced generation of phosphatidylinositol(3,4,5)triphosphate (PtdIns(3,4,5)P3) in Pik3r1-/- adipocytes and facilitation of Glut4 translocation from the low-density microsome (LDM) fraction to the plasma membrane (PM). |
| 677 | 9988280 | Increased insulin sensitivity and hypoglycaemia in mice lacking the p85 alpha subunit of phosphoinositide 3-kinase. |
| 678 | 9988280 | Although a role for phosphoinositide-3-kinase (PI3K) activity in insulin-stimulated glucose transport and glucose transporter isoform 4 (Glut4) translocation has been suggested in vitro, its role in vivo and the molecular link between activation of PI3K and translocation has not yet been elucidated. |
| 679 | 9988280 | To determine the role of PI3K in glucose homeostasis, we generated mice with a targeted disruption of the gene encoding the p85alpha regulatory subunit of PI3K (Pik3r1; refs 3-5). |
| 680 | 9988280 | Insulin-stimulated PI3K activity associated with insulin receptor substrates (IRSs) was mediated via full-length p85 alpha in wild-type mice, but via the p50 alpha alternative splicing isoform of the same gene in Pik3r1-/- mice. |
| 681 | 9988280 | This isoform switch was associated with an increase in insulin-induced generation of phosphatidylinositol(3,4,5)triphosphate (PtdIns(3,4,5)P3) in Pik3r1-/- adipocytes and facilitation of Glut4 translocation from the low-density microsome (LDM) fraction to the plasma membrane (PM). |
| 682 | 9988280 | Increased insulin sensitivity and hypoglycaemia in mice lacking the p85 alpha subunit of phosphoinositide 3-kinase. |
| 683 | 9988280 | Although a role for phosphoinositide-3-kinase (PI3K) activity in insulin-stimulated glucose transport and glucose transporter isoform 4 (Glut4) translocation has been suggested in vitro, its role in vivo and the molecular link between activation of PI3K and translocation has not yet been elucidated. |
| 684 | 9988280 | To determine the role of PI3K in glucose homeostasis, we generated mice with a targeted disruption of the gene encoding the p85alpha regulatory subunit of PI3K (Pik3r1; refs 3-5). |
| 685 | 9988280 | Insulin-stimulated PI3K activity associated with insulin receptor substrates (IRSs) was mediated via full-length p85 alpha in wild-type mice, but via the p50 alpha alternative splicing isoform of the same gene in Pik3r1-/- mice. |
| 686 | 9988280 | This isoform switch was associated with an increase in insulin-induced generation of phosphatidylinositol(3,4,5)triphosphate (PtdIns(3,4,5)P3) in Pik3r1-/- adipocytes and facilitation of Glut4 translocation from the low-density microsome (LDM) fraction to the plasma membrane (PM). |
| 687 | 10078574 | Hyperglycemia inhibits insulin activation of Akt/protein kinase B but not phosphatidylinositol 3-kinase in rat skeletal muscle. |
| 688 | 10078574 | Studies of insulin signaling in the latter muscles revealed that activation of Akt/protein kinase B (PKB) was diminished by 60%, compared with that of muscles preincubated in a glucose-free medium; whereas activation of phosphatidylinositol (PI) 3-kinase, an upstream regulator of Akt/PKB in the insulin-signaling cascade, and of mitogen-activated protein (MAP) kinase, a parallel signal, was unaffected. |
| 689 | 10078574 | They suggest that impairment of insulin action in these muscles is related to inhibition of Akt/PKB by events that do not affect PI 3-kinase. |
| 690 | 10096790 | Defective regulation of phosphatidylinositol-3-kinase gene expression in skeletal muscle and adipose tissue of non-insulin-dependent diabetes mellitus patients. |
| 691 | 10096790 | We investigated the regulation of the mRNA expression of the insulin receptor, insulin receptor substrate-1 (IRS-1) and p85alpha-phosphatidylinositol-3-kinase (PI-3K), three major actors of insulin action, in skeletal muscle from 10 healthy lean volunteers, 13 obese patients with Type II (non-insulin-dependent) diabetes mellitus and 7 non-diabetic obese subjects. |
| 692 | 10096790 | In contrast, insulin increased p85alpha-phosphatidylinositol-3-kinase mRNA expression in muscle from non-diabetic subjects (+98+/-22% in lean and +127+/-16% in obese, p<0.02) but this effect was totally impaired in Type II diabetic patients (+5+/-12%, NS). |
| 693 | 10096790 | A similar defect in insulin action on p85alpha-phosphatidylinositol-3-kinase mRNA expression was observed in abdominal subcutaneous adipose tissue (+138+/-25%, p<0.01 in lean and +46+/-14%, p<0.02 in obese and +29+/-11%, NS in Type II diabetic patients). |
| 694 | 10096790 | The lack of action of insulin on p85alpha-phosphatidylinositol-3-kinase mRNA in diabetic subjects was probably not due to a deleterious effect of hyperglycaemia since improvement of the glycaemic control for 10 days did not restore the response in muscle or in adipose tissue. |
| 695 | 10096790 | This study provides evidence for a defect in the regulation by insulin of PI-3K gene expression in Type II diabetic patients, thus reinforcing the concept that alterations at the gene expression might be involved in the pathogeny of Type II diabetes. |
| 696 | 10096790 | Defective regulation of phosphatidylinositol-3-kinase gene expression in skeletal muscle and adipose tissue of non-insulin-dependent diabetes mellitus patients. |
| 697 | 10096790 | We investigated the regulation of the mRNA expression of the insulin receptor, insulin receptor substrate-1 (IRS-1) and p85alpha-phosphatidylinositol-3-kinase (PI-3K), three major actors of insulin action, in skeletal muscle from 10 healthy lean volunteers, 13 obese patients with Type II (non-insulin-dependent) diabetes mellitus and 7 non-diabetic obese subjects. |
| 698 | 10096790 | In contrast, insulin increased p85alpha-phosphatidylinositol-3-kinase mRNA expression in muscle from non-diabetic subjects (+98+/-22% in lean and +127+/-16% in obese, p<0.02) but this effect was totally impaired in Type II diabetic patients (+5+/-12%, NS). |
| 699 | 10096790 | A similar defect in insulin action on p85alpha-phosphatidylinositol-3-kinase mRNA expression was observed in abdominal subcutaneous adipose tissue (+138+/-25%, p<0.01 in lean and +46+/-14%, p<0.02 in obese and +29+/-11%, NS in Type II diabetic patients). |
| 700 | 10096790 | The lack of action of insulin on p85alpha-phosphatidylinositol-3-kinase mRNA in diabetic subjects was probably not due to a deleterious effect of hyperglycaemia since improvement of the glycaemic control for 10 days did not restore the response in muscle or in adipose tissue. |
| 701 | 10096790 | This study provides evidence for a defect in the regulation by insulin of PI-3K gene expression in Type II diabetic patients, thus reinforcing the concept that alterations at the gene expression might be involved in the pathogeny of Type II diabetes. |
| 702 | 10096790 | Defective regulation of phosphatidylinositol-3-kinase gene expression in skeletal muscle and adipose tissue of non-insulin-dependent diabetes mellitus patients. |
| 703 | 10096790 | We investigated the regulation of the mRNA expression of the insulin receptor, insulin receptor substrate-1 (IRS-1) and p85alpha-phosphatidylinositol-3-kinase (PI-3K), three major actors of insulin action, in skeletal muscle from 10 healthy lean volunteers, 13 obese patients with Type II (non-insulin-dependent) diabetes mellitus and 7 non-diabetic obese subjects. |
| 704 | 10096790 | In contrast, insulin increased p85alpha-phosphatidylinositol-3-kinase mRNA expression in muscle from non-diabetic subjects (+98+/-22% in lean and +127+/-16% in obese, p<0.02) but this effect was totally impaired in Type II diabetic patients (+5+/-12%, NS). |
| 705 | 10096790 | A similar defect in insulin action on p85alpha-phosphatidylinositol-3-kinase mRNA expression was observed in abdominal subcutaneous adipose tissue (+138+/-25%, p<0.01 in lean and +46+/-14%, p<0.02 in obese and +29+/-11%, NS in Type II diabetic patients). |
| 706 | 10096790 | The lack of action of insulin on p85alpha-phosphatidylinositol-3-kinase mRNA in diabetic subjects was probably not due to a deleterious effect of hyperglycaemia since improvement of the glycaemic control for 10 days did not restore the response in muscle or in adipose tissue. |
| 707 | 10096790 | This study provides evidence for a defect in the regulation by insulin of PI-3K gene expression in Type II diabetic patients, thus reinforcing the concept that alterations at the gene expression might be involved in the pathogeny of Type II diabetes. |
| 708 | 10096790 | Defective regulation of phosphatidylinositol-3-kinase gene expression in skeletal muscle and adipose tissue of non-insulin-dependent diabetes mellitus patients. |
| 709 | 10096790 | We investigated the regulation of the mRNA expression of the insulin receptor, insulin receptor substrate-1 (IRS-1) and p85alpha-phosphatidylinositol-3-kinase (PI-3K), three major actors of insulin action, in skeletal muscle from 10 healthy lean volunteers, 13 obese patients with Type II (non-insulin-dependent) diabetes mellitus and 7 non-diabetic obese subjects. |
| 710 | 10096790 | In contrast, insulin increased p85alpha-phosphatidylinositol-3-kinase mRNA expression in muscle from non-diabetic subjects (+98+/-22% in lean and +127+/-16% in obese, p<0.02) but this effect was totally impaired in Type II diabetic patients (+5+/-12%, NS). |
| 711 | 10096790 | A similar defect in insulin action on p85alpha-phosphatidylinositol-3-kinase mRNA expression was observed in abdominal subcutaneous adipose tissue (+138+/-25%, p<0.01 in lean and +46+/-14%, p<0.02 in obese and +29+/-11%, NS in Type II diabetic patients). |
| 712 | 10096790 | The lack of action of insulin on p85alpha-phosphatidylinositol-3-kinase mRNA in diabetic subjects was probably not due to a deleterious effect of hyperglycaemia since improvement of the glycaemic control for 10 days did not restore the response in muscle or in adipose tissue. |
| 713 | 10096790 | This study provides evidence for a defect in the regulation by insulin of PI-3K gene expression in Type II diabetic patients, thus reinforcing the concept that alterations at the gene expression might be involved in the pathogeny of Type II diabetes. |
| 714 | 10096790 | Defective regulation of phosphatidylinositol-3-kinase gene expression in skeletal muscle and adipose tissue of non-insulin-dependent diabetes mellitus patients. |
| 715 | 10096790 | We investigated the regulation of the mRNA expression of the insulin receptor, insulin receptor substrate-1 (IRS-1) and p85alpha-phosphatidylinositol-3-kinase (PI-3K), three major actors of insulin action, in skeletal muscle from 10 healthy lean volunteers, 13 obese patients with Type II (non-insulin-dependent) diabetes mellitus and 7 non-diabetic obese subjects. |
| 716 | 10096790 | In contrast, insulin increased p85alpha-phosphatidylinositol-3-kinase mRNA expression in muscle from non-diabetic subjects (+98+/-22% in lean and +127+/-16% in obese, p<0.02) but this effect was totally impaired in Type II diabetic patients (+5+/-12%, NS). |
| 717 | 10096790 | A similar defect in insulin action on p85alpha-phosphatidylinositol-3-kinase mRNA expression was observed in abdominal subcutaneous adipose tissue (+138+/-25%, p<0.01 in lean and +46+/-14%, p<0.02 in obese and +29+/-11%, NS in Type II diabetic patients). |
| 718 | 10096790 | The lack of action of insulin on p85alpha-phosphatidylinositol-3-kinase mRNA in diabetic subjects was probably not due to a deleterious effect of hyperglycaemia since improvement of the glycaemic control for 10 days did not restore the response in muscle or in adipose tissue. |
| 719 | 10096790 | This study provides evidence for a defect in the regulation by insulin of PI-3K gene expression in Type II diabetic patients, thus reinforcing the concept that alterations at the gene expression might be involved in the pathogeny of Type II diabetes. |
| 720 | 10096790 | Defective regulation of phosphatidylinositol-3-kinase gene expression in skeletal muscle and adipose tissue of non-insulin-dependent diabetes mellitus patients. |
| 721 | 10096790 | We investigated the regulation of the mRNA expression of the insulin receptor, insulin receptor substrate-1 (IRS-1) and p85alpha-phosphatidylinositol-3-kinase (PI-3K), three major actors of insulin action, in skeletal muscle from 10 healthy lean volunteers, 13 obese patients with Type II (non-insulin-dependent) diabetes mellitus and 7 non-diabetic obese subjects. |
| 722 | 10096790 | In contrast, insulin increased p85alpha-phosphatidylinositol-3-kinase mRNA expression in muscle from non-diabetic subjects (+98+/-22% in lean and +127+/-16% in obese, p<0.02) but this effect was totally impaired in Type II diabetic patients (+5+/-12%, NS). |
| 723 | 10096790 | A similar defect in insulin action on p85alpha-phosphatidylinositol-3-kinase mRNA expression was observed in abdominal subcutaneous adipose tissue (+138+/-25%, p<0.01 in lean and +46+/-14%, p<0.02 in obese and +29+/-11%, NS in Type II diabetic patients). |
| 724 | 10096790 | The lack of action of insulin on p85alpha-phosphatidylinositol-3-kinase mRNA in diabetic subjects was probably not due to a deleterious effect of hyperglycaemia since improvement of the glycaemic control for 10 days did not restore the response in muscle or in adipose tissue. |
| 725 | 10096790 | This study provides evidence for a defect in the regulation by insulin of PI-3K gene expression in Type II diabetic patients, thus reinforcing the concept that alterations at the gene expression might be involved in the pathogeny of Type II diabetes. |
| 726 | 10101263 | The mutated gene product, ATM, has a domain possessing homology to phosphatidylinositol-3-kinase and has been shown to possess protein kinase activity. |
| 727 | 10102697 | Islet transplantation restores normal levels of insulin receptor and substrate tyrosine phosphorylation and phosphatidylinositol 3-kinase activity in skeletal muscle and myocardium of streptozocin-induced diabetic rats. |
| 728 | 10102697 | Compared with controls, diabetic rats were characterized by multiple insulin signaling abnormalities in skeletal muscle, which included 1) increased insulin-stimulated tyrosine phosphorylation of the insulin receptor beta-subunit and insulin receptor substrates IRS-1 and IRS-2, 2) increased substrate tyrosine phosphorylation in the basal state, 3) a decreased amount of IRS-1 protein, 4) markedly elevated basal and insulin-stimulated phosphatidylinositol (PI) 3-kinase activity in anti-IRS-1 immunoprecipitates from total tissue extracts, and 5) increased PI 3-kinase activity in low-density microsomes. |
| 729 | 10102697 | In addition, STZ-diabetes resulted in decreased IRS-1 and increased IRS-2 protein levels in myocardium. |
| 730 | 10102697 | Islet transplantation fully corrected the diabetes-induced changes in protein tyrosine phosphorylation and PI 3-kinase activity and normalized IRS-1 and IRS-2 protein content in both skeletal muscle and myocardium. |
| 731 | 10187855 | Oxidative stress disrupts insulin-induced cellular redistribution of insulin receptor substrate-1 and phosphatidylinositol 3-kinase in 3T3-L1 adipocytes. |
| 732 | 10187855 | A putative cellular mechanism for impaired protein kinase B activation and GLUT4 translocation. |
| 733 | 10187855 | In a recent study we have demonstrated that 3T3-L1 adipocytes exposed to low micromolar H2O2 concentrations display impaired insulin stimulated GLUT4 translocation from internal membrane pools to the plasma membrane (Rudich, A., Tirosh, A., Potashnik, R., Hemi, R., Kannety, H., and Bashan, N. (1998) Diabetes 47, 1562-1569). |
| 734 | 10187855 | This was associated with reduced insulin-stimulated IRS-1 and p85-associated PI 3-kinase activities in the LDM (84 and 96% inhibition, respectively). |
| 735 | 10187855 | The effect of this finding on the downstream insulin signal was demonstrated by a 90% reduction in insulin stimulated protein kinase B (PKB) serine 473 phosphorylation and impaired activation of PKBalpha and PKBgamma. |
| 736 | 10187855 | These data suggest that activation of PKB and GLUT4 translocation are insulin signaling events dependent upon a normal insulin induced cellular compartmentalization of PI 3-kinase and IRS-1, which is oxidative stress-sensitive. |
| 737 | 10318852 | Membrane-targeted phosphatidylinositol 3-kinase mimics insulin actions and induces a state of cellular insulin resistance. |
| 738 | 10318852 | Even at this submaximal PI 3-kinase activity, p110(CAAX) fully stimulated p70 S6 kinase, Akt, 2-deoxyglucose uptake, and Ras, whereas, p110(WT) had little or no effect on these downstream effects. |
| 739 | 10318852 | Interestingly p110(CAAX) did not activate MAP kinase, despite its stimulation of p21(ras). |
| 740 | 10318852 | Surprisingly, p110(CAAX) did not increase basal glycogen synthase activity, and inhibited insulin stimulated activity, indicative of cellular resistance to this action of insulin. p110(CAAX) also inhibited insulin stimulated, but not platelet-derived growth factor-stimulated mitogen-activated protein kinase phosphorylation, demonstrating that the p110(CAAX) induced inhibition of mitogen-activated protein kinase and insulin signaling is specific, and not due to some toxic or nonspecific effect on the cells. |
| 741 | 10318852 | Moreover, p110(CAAX) stimulated IRS-1 Ser/Thr phosphorylation, and inhibited IRS-1 associated PI 3-kinase activity, without affecting insulin receptor tyrosine phosphorylation, suggesting that it may play an important role as a negative regulator for insulin signaling. |
| 742 | 10320056 | Insulin-mediated pseudoacromegaly in a patient with severe insulin resistance: association of defective insulin-stimulated glucose transport with impaired phosphatidylinositol 3-kinase activity in fibroblasts. |
| 743 | 10320056 | In cultured fibroblasts derived from the patient, (i) insulin-stimulated glucose transport, (ii) the subcellular distribution of GLUT1 glucose transporters, (iii) insulin-stimulated IRS-1-immunoprecipitable phosphatidylinositol (PI) 3-kinase activity, as well as (iv) protein expression of the small GTP-binding protein Rab4 was determined. |
| 744 | 10320056 | The results indicate, that insulin's ability to stimulate glucose transport is defective in the patients fibroblasts although the GLUT1 content in the plasma membrane was increased by 34% when compared to control cells. |
| 745 | 10320056 | Furthermore, the IRS-1 dependent activation of PI 3-kinase was reduced by 39.6% after incubation with 10 nM insulin for 5 min. |
| 746 | 10329736 | Interaction of insulin receptor substrate 3 with insulin receptor, insulin receptor-related receptor, insulin-like growth factor-1 receptor, and downstream signaling proteins. |
| 747 | 10329736 | IRS3 is considerably shorter than IRS1, IRS2, and IRS4, and is predicted to interact with a distinct group of downstream signaling molecules. |
| 748 | 10329736 | As determined in a modified yeast two-hybrid system, mIRS3 bound strongly to the p85 subunit of phosphatidylinositol 3-kinase. |
| 749 | 10329736 | Although high affinity interaction required the presence of at least two of the four YXXM motifs in mIRS3, there was not a requirement for specific YXXM motifs. mIRS3 also bound to SHP2, Grb2, Nck, and Shc, but less strongly than to p85. |
| 750 | 10329736 | Insulin stimulation promoted the association of mIRS3 with p85, SHP2, Nck, and Shc. |
| 751 | 10329736 | Despite weak association between mIRS3 and Grb2, this interaction was not increased by insulin, and may not be mediated by the SH2 domain of Grb2. |
| 752 | 10329736 | Thus, in contrast to other IRS proteins, mIRS3 appears to have greater specificity for activation of the phosphatidylinositol 3-kinase pathway rather than the Grb2/Ras pathway. |
| 753 | 10329736 | Interaction of insulin receptor substrate 3 with insulin receptor, insulin receptor-related receptor, insulin-like growth factor-1 receptor, and downstream signaling proteins. |
| 754 | 10329736 | IRS3 is considerably shorter than IRS1, IRS2, and IRS4, and is predicted to interact with a distinct group of downstream signaling molecules. |
| 755 | 10329736 | As determined in a modified yeast two-hybrid system, mIRS3 bound strongly to the p85 subunit of phosphatidylinositol 3-kinase. |
| 756 | 10329736 | Although high affinity interaction required the presence of at least two of the four YXXM motifs in mIRS3, there was not a requirement for specific YXXM motifs. mIRS3 also bound to SHP2, Grb2, Nck, and Shc, but less strongly than to p85. |
| 757 | 10329736 | Insulin stimulation promoted the association of mIRS3 with p85, SHP2, Nck, and Shc. |
| 758 | 10329736 | Despite weak association between mIRS3 and Grb2, this interaction was not increased by insulin, and may not be mediated by the SH2 domain of Grb2. |
| 759 | 10329736 | Thus, in contrast to other IRS proteins, mIRS3 appears to have greater specificity for activation of the phosphatidylinositol 3-kinase pathway rather than the Grb2/Ras pathway. |
| 760 | 10329986 | Leptin opposes insulin's effects on fatty acid partitioning in muscles isolated from obese ob/ob mice. |
| 761 | 10329986 | Because muscle triacylglycerol (TAG) accumulation might contribute to insulin resistance in leptin-deficient ob/ob mice, we studied the acute (60- to 90-min) effects of leptin and insulin on [14C]glucose and [14C]oleate metabolism in muscles isolated from lean and obese ob/ob mice. |
| 762 | 10329986 | Adding leptin diminished insulin's antioxidative, lipogenic effects. |
| 763 | 10329986 | In soleus from lean mice, insulin increased the partitioning ratio 142%, whereas leptin decreased it 51%, as previously reported (Muoio, D. |
| 764 | 10329986 | The phosphatidylinositol 3-kinase inhibitor wortmannin blocked insulin's effects on lipid metabolism but only attenuated leptin's effects. |
| 765 | 10329986 | These data indicate that leptin opposes insulin's promotion of TAG accumulation in lean and ob/ob muscles. |
| 766 | 10329986 | Because acute leptin exposure does not correct insulin resistance in ob/ob muscles, in vivo improvements in glucose homeostasis appear to require other long-term factors, possibly TAG depletion. |
| 767 | 10330234 | Wortmannin inhibits insulin-stimulated activation of protein phosphatase 1 in rat cardiomyocytes. |
| 768 | 10330234 | Phosphatidylinositol 3-kinase (PI3K) has been implicated in the insulin-induced activation of glycogen synthase, although the true function of this enzyme remains unclear. |
| 769 | 10330234 | Data presented here demonstrate that the PI3K inhibitors wortmannin and LY-294002 block the insulin-stimulated activation of protein phosphatase 1 (PP1) in rat ventricular cardiomyocytes. |
| 770 | 10330234 | This loss of phosphatase activation mimics that seen in diabetic cardiomyocytes, in which insulin stimulation fails to activate both PP1 and glycogen synthase. |
| 771 | 10330234 | Interestingly, in diabetic cells, insulin stimulated PI3K activity to 300% of that in untreated controls, whereas this activity was increased by only 77% in normal cells. |
| 772 | 10330234 | Our results indicate that PI3K is involved in the stimulation of glycogen synthase activity by insulin through the regulation of PP1. |
| 773 | 10330234 | The inability of insulin to stimulate phosphatase activity in diabetic cells, despite a significant increase in PI3K activity, suggests a defect in the insulin signaling pathway that contributes to the pathology of insulin-dependent diabetes. |
| 774 | 10330234 | Wortmannin inhibits insulin-stimulated activation of protein phosphatase 1 in rat cardiomyocytes. |
| 775 | 10330234 | Phosphatidylinositol 3-kinase (PI3K) has been implicated in the insulin-induced activation of glycogen synthase, although the true function of this enzyme remains unclear. |
| 776 | 10330234 | Data presented here demonstrate that the PI3K inhibitors wortmannin and LY-294002 block the insulin-stimulated activation of protein phosphatase 1 (PP1) in rat ventricular cardiomyocytes. |
| 777 | 10330234 | This loss of phosphatase activation mimics that seen in diabetic cardiomyocytes, in which insulin stimulation fails to activate both PP1 and glycogen synthase. |
| 778 | 10330234 | Interestingly, in diabetic cells, insulin stimulated PI3K activity to 300% of that in untreated controls, whereas this activity was increased by only 77% in normal cells. |
| 779 | 10330234 | Our results indicate that PI3K is involved in the stimulation of glycogen synthase activity by insulin through the regulation of PP1. |
| 780 | 10330234 | The inability of insulin to stimulate phosphatase activity in diabetic cells, despite a significant increase in PI3K activity, suggests a defect in the insulin signaling pathway that contributes to the pathology of insulin-dependent diabetes. |
| 781 | 10330234 | Wortmannin inhibits insulin-stimulated activation of protein phosphatase 1 in rat cardiomyocytes. |
| 782 | 10330234 | Phosphatidylinositol 3-kinase (PI3K) has been implicated in the insulin-induced activation of glycogen synthase, although the true function of this enzyme remains unclear. |
| 783 | 10330234 | Data presented here demonstrate that the PI3K inhibitors wortmannin and LY-294002 block the insulin-stimulated activation of protein phosphatase 1 (PP1) in rat ventricular cardiomyocytes. |
| 784 | 10330234 | This loss of phosphatase activation mimics that seen in diabetic cardiomyocytes, in which insulin stimulation fails to activate both PP1 and glycogen synthase. |
| 785 | 10330234 | Interestingly, in diabetic cells, insulin stimulated PI3K activity to 300% of that in untreated controls, whereas this activity was increased by only 77% in normal cells. |
| 786 | 10330234 | Our results indicate that PI3K is involved in the stimulation of glycogen synthase activity by insulin through the regulation of PP1. |
| 787 | 10330234 | The inability of insulin to stimulate phosphatase activity in diabetic cells, despite a significant increase in PI3K activity, suggests a defect in the insulin signaling pathway that contributes to the pathology of insulin-dependent diabetes. |
| 788 | 10330234 | Wortmannin inhibits insulin-stimulated activation of protein phosphatase 1 in rat cardiomyocytes. |
| 789 | 10330234 | Phosphatidylinositol 3-kinase (PI3K) has been implicated in the insulin-induced activation of glycogen synthase, although the true function of this enzyme remains unclear. |
| 790 | 10330234 | Data presented here demonstrate that the PI3K inhibitors wortmannin and LY-294002 block the insulin-stimulated activation of protein phosphatase 1 (PP1) in rat ventricular cardiomyocytes. |
| 791 | 10330234 | This loss of phosphatase activation mimics that seen in diabetic cardiomyocytes, in which insulin stimulation fails to activate both PP1 and glycogen synthase. |
| 792 | 10330234 | Interestingly, in diabetic cells, insulin stimulated PI3K activity to 300% of that in untreated controls, whereas this activity was increased by only 77% in normal cells. |
| 793 | 10330234 | Our results indicate that PI3K is involved in the stimulation of glycogen synthase activity by insulin through the regulation of PP1. |
| 794 | 10330234 | The inability of insulin to stimulate phosphatase activity in diabetic cells, despite a significant increase in PI3K activity, suggests a defect in the insulin signaling pathway that contributes to the pathology of insulin-dependent diabetes. |
| 795 | 10330234 | Wortmannin inhibits insulin-stimulated activation of protein phosphatase 1 in rat cardiomyocytes. |
| 796 | 10330234 | Phosphatidylinositol 3-kinase (PI3K) has been implicated in the insulin-induced activation of glycogen synthase, although the true function of this enzyme remains unclear. |
| 797 | 10330234 | Data presented here demonstrate that the PI3K inhibitors wortmannin and LY-294002 block the insulin-stimulated activation of protein phosphatase 1 (PP1) in rat ventricular cardiomyocytes. |
| 798 | 10330234 | This loss of phosphatase activation mimics that seen in diabetic cardiomyocytes, in which insulin stimulation fails to activate both PP1 and glycogen synthase. |
| 799 | 10330234 | Interestingly, in diabetic cells, insulin stimulated PI3K activity to 300% of that in untreated controls, whereas this activity was increased by only 77% in normal cells. |
| 800 | 10330234 | Our results indicate that PI3K is involved in the stimulation of glycogen synthase activity by insulin through the regulation of PP1. |
| 801 | 10330234 | The inability of insulin to stimulate phosphatase activity in diabetic cells, despite a significant increase in PI3K activity, suggests a defect in the insulin signaling pathway that contributes to the pathology of insulin-dependent diabetes. |
| 802 | 10331419 | Endothelin-1 modulates insulin signaling through phosphatidylinositol 3-kinase pathway in vascular smooth muscle cells. |
| 803 | 10331419 | ET-1 increased the level of serine phosphorylation of insulin receptor beta subunit but increased both tyrosine and serine phosphorylation of insulin receptor substrate (IRS)-2. |
| 804 | 10331419 | Pretreatment of cells with ET-1 (10 nmol/l) inhibited insulin-stimulated PI 3-kinase activity associated with IRS-2 by 50-60% and inhibited the association of p85 subunit of PI 3-kinase to IRS-2. |
| 805 | 10331419 | The inhibition of insulin-stimulated PI 3-kinase activity by ET-1 was prevented by BQ-123, a selective ET(A) receptor antagonist, but was not affected by pertussis toxin. |
| 806 | 10331419 | Treatment of cells with phorbol 12-myristate 13-acetate, an activator of protein kinase C (PKC), reduced both insulin-stimulated PI 3-kinase activity by 57% and the association of IRS-2 to the p85 subunit of PI 3-kinase by 40%, whereas GF109203X, a specific inhibitor of PKC, partially prevented the inhibitory effect of ET-1 on insulin-induced PI 3-kinase activity. |
| 807 | 10331419 | These results suggested that ET-1 could interfere with insulin signaling in SMCs by both PKC-dependent and -independent pathways. |
| 808 | 10334301 | Regulation of ob gene expression and leptin secretion by insulin and dexamethasone in rat adipocytes. |
| 809 | 10334301 | To better understand the molecular mechanisms of hormone-regulated leptin synthesis and secretion, we assessed the ability of insulin and dexamethasone to acutely modulate ob gene expression and leptin secretion in rat adipocytes. |
| 810 | 10334301 | Incubation of rat adipocytes with 100 nmol/l insulin for 2 h had no effect on ob mRNA levels, but it stimulated a twofold increase in leptin secretion. |
| 811 | 10334301 | Consonant with a posttranscriptional and transcriptional regulatory mechanism for insulin- and dexamethasone-stimulated leptin secretion, respectively, actinomycin D blocked dexamethasone-stimulated leptin secretion but did not affect insulin-stimulated leptin secretion. |
| 812 | 10334301 | Interestingly, however, insulin was still able to stimulate a twofold increase in leptin secretion. |
| 813 | 10334301 | These data suggest that insulin, but not dexamethasone, is able to stimulate leptin secretion from a preexisting intracellular pool, although de novo protein synthesis is required for the full insulin-stimulated effect. |
| 814 | 10334301 | The phosphatidylinositol 3-kinase inhibitor LY294002, the Map/Erk kinase inhibitor PD98059, and the immunosuppressant rapamycin had no effect on basal levels of leptin secretion. |
| 815 | 10334301 | However, all three inhibitors markedly decreased both insulin- and dexamethasone-stimulated leptin secretion. |
| 816 | 10334301 | These findings suggest a complex set of signaling pathways involved in mediating insulin- and dexamethasone-stimulated leptin synthesis and secretion. |
| 817 | 10342814 | The mouse ob gene encodes leptin, an adipocyte hormone that regulates body weight and energy expenditure. |
| 818 | 10342814 | In lean mice, leptin acutely increases glucose metabolism in an insulin-independent manner, which could account, at least in part, for some of the antidiabetic effect of the hormone. |
| 819 | 10342814 | To investigate further the acute effect of leptin on glucose metabolism in insulin-resistant obese diabetic mice, leptin (40 ng x g(-1) x h(-1)) was administered intravenously for 6 h in C57Bl/6J ob/ob mice. |
| 820 | 10342814 | Plasma insulin concentration increased moderately but neither glucose, glucagon, thyroid hormones, growth hormone, nor IGF-1 levels were different from phosphate-buffered saline-infused C57Bl/6J ob/ob mice. |
| 821 | 10342814 | In addition, leptin stimulated hepatic glucose production, which was associated with increased glucose-6-phosphatase activity. |
| 822 | 10342814 | Interestingly, hepatic insulin receptor substrate (IRS)1-associated phosphatidylinositol 3-kinase activity was slightly elevated, but neither the content of glucose transporter GLUT2 nor the phosphorylation state of the insulin receptor and IRS-1 were changed by acute leptin treatment. |
| 823 | 10342814 | Insulin resistance of skeletal muscle and WAT, while not affected by acute leptin treatment, could also be corrected in the long term and account for some of leptin's antidiabetic effects. |
| 824 | 10389840 | Membrane glycoprotein plasma cell 1 (PC-1) has been shown to be increased in type 2 diabetes and involved in insulin resistance through inhibiting the insulin receptor tyrosine kinase, which was demonstrated using cultured breast cancer cells. |
| 825 | 10389840 | Thus, we considered it necessary to investigate the effect of PC-1 using highly insulin-sensitive cells. |
| 826 | 10389840 | Here, we used two of the following approaches: 1) investigating PC-1 expression levels in insulin-responsive tissues in rat models of diabetes and 2) overexpressing PC-1 in 3T3-L1 adipocytes. |
| 827 | 10389840 | We found that PC-1 was highly expressed in insulin-responsive tissues, such as liver and adipose tissue, in normal rats. |
| 828 | 10389840 | Thus, PC-1 expression levels were not associated with high-fat-diet-induced insulin resistance or hyperglycemia. |
| 829 | 10389840 | However, insulin-induced tyrosine phosphorylation of the insulin receptor and insulin receptor substrate 1, activation of phosphatidylinositol 3-kinase, and glucose uptake were not affected by PC-1 overexpression. |
| 830 | 10389840 | These results strongly suggest that increased PC-1 expression is not causally related to insulin resistance. |
| 831 | 10414926 | Insulin inhibits glucagon secretion by the activation of PI3-kinase in In-R1-G9 cells. |
| 832 | 10414926 | In this study, we confirmed that, in In-R1-G9 cells, a pancreatic alpha cell line, insulin stimulated phosphorylation of insulin receptor substrate-1 (IRS-1) and activated phosphatidylinositol 3-kinase (PI3-kinase). |
| 833 | 10414926 | We further studied, using wortmannin, an inhibitor of PI3-kinase, whether the inhibitory effect of insulin on glucagon secretion was mediated through PI3-kinase pathway in these cells. |
| 834 | 10414926 | Insulin increased the amount of 85 kDa subunit of PI3-kinase in plasma membrane fraction (PM), with a reciprocal decrease of the kinase in cytosol fraction (CY). |
| 835 | 10414926 | Insulin also increased PI3-kinase activity in PM, but not in CY. |
| 836 | 10414926 | Recruitment and activation of PI3-kinase in plasma membrane might be relevant at least in part to insulin-induced inhibition of glucagon release. |
| 837 | 10418851 | Assessments of the response to hyperglycemic-hyperinsulinemic clamping have shown that abnormalities of muscle glycogen synthesis, apparently mediated by a defect in GLUT-4 transport and/or hexokinase activity, play a major role in causing insulin resistance in type 2 diabetes. |
| 838 | 10418851 | Studies of the mechanisms by which free fatty acids (FFA) cause insulin resistance in humans indicate that increased FFA levels inhibit glucose transport, which may be a consequence of decreased insulin receptor substrate (IRS-1)-associated phosphatidylinositol 3-kinase activity. 13C NMR spectroscopy studies have documented that liver glycogen concentrations are reduced and the rate of hepatic gluconeogenesis is increased in subjects with type 2 diabetes; thus, the higher rate of glucose production in type 2 diabetes can be attributed entirely to increased rates of hepatic gluconeogenesis. |
| 839 | 10430617 | The Gly972-->Arg amino acid polymorphism in IRS-1 impairs insulin secretion in pancreatic beta cells. |
| 840 | 10430617 | Carriers of the Arg(972) substitution are characterized by lower fasting insulin and C-peptide levels compared with non-carriers, suggesting that the Arg(972) IRS-1 variant may contribute to impairment of insulin secretion. |
| 841 | 10430617 | In this study, we stably overexpressed both wild-type IRS-1 (RIN-WT) and Arg(972) IRS-1 variant (RIN-Arg(972)) in RIN beta cells to investigate directly whether the polymorphism in codon 972 of IRS-1 impairs insulin secretion. |
| 842 | 10430617 | The Arg(972) IRS-1 variant did not affect expression or function of endogenous IRS-2. |
| 843 | 10430617 | RIN-WT showed a marked increase in both glucose- and insulin-stimulated tyrosine phosphorylation of IRS-1 compared with control RIN cells. |
| 844 | 10430617 | The Arg(972) IRS-1 variant did not alter the extent of either glucose- or insulin-stimulated tyrosine phosphorylation of recombinant IRS-1. |
| 845 | 10430617 | However, RIN-Arg(972) showed a significant decrease in binding of the p85 subunit of phosphatidylinositol-3-kinase (PI 3-kinase) with IRS-1, compared with RIN-WT. |
| 846 | 10430617 | By contrast, RIN cells expressing Arg(972) IRS-1 exhibited a marked decrease in both glucose- and sulfonylurea-stimulated insulin secretion compared with RIN-WT. |
| 847 | 10430617 | These data suggest that the insulin signaling pathway involving the IRS-1/PI 3-kinase may play an important role in the insulin secretory process in pancreatic beta cells. |
| 848 | 10430617 | More importantly, the results suggest that the common Arg(972) IRS-1 polymorphism may impair glucose-stimulated insulin secretion, thus contributing to the relative insulin deficiency observed in carriers of this variant. |
| 849 | 10440129 | Glucagon-like peptide-1 promotes DNA synthesis, activates phosphatidylinositol 3-kinase and increases transcription factor pancreatic and duodenal homeobox gene 1 (PDX-1) DNA binding activity in beta (INS-1)-cells. |
| 850 | 10449437 | In this report, insulin signaling on the phosphatidylinositol 3-kinase (PI 3-kinase) and mitogen-activated protein (MAP) kinase pathways were compared in vascular tissues of lean and obese Zucker (fa/fa) rats in both ex vivo and in vivo studies. |
| 851 | 10449437 | Ex vivo, insulin-stimulated tyrosine phosphorylation of insulin receptor beta subunits (IRbeta) in the aorta and microvessels of obese rats was significantly decreased compared with lean rats, although the protein levels of IRbeta in the 2 groups were not different. |
| 852 | 10449437 | Insulin-induced tyrosine phosphorylation of insulin receptor substrates 1 and 2 (IRS-1 and IRS-2) and their protein levels were decreased in the aorta of obese rats compared with lean rats. |
| 853 | 10449437 | The association of p85 subunit to the IRS proteins and the IRS-associated PI 3-kinase activities stimulated by insulin in the aorta of obese rats were significantly decreased compared with the lean rats. |
| 854 | 10449437 | In addition, insulin-stimulated serine phosphorylation of Akt, a downstream kinase of PI 3-kinase pathway, was also reduced significantly in isolated microvessels from obese rats compared with the lean rats. |
| 855 | 10449437 | In contrast, insulin stimulated tyrosine phosphorylation of MAP kinase (ERK-1/2) equally in isolated microvessels of lean and obese rats, although basal tyrosine phosphorylation of ERK-1/2 was higher in the obese rats. |
| 856 | 10449437 | To our knowledge, these data provided the first direct measurements of insulin signaling in the vascular tissues, and documented a selective resistance to PI 3-kinase (but not to MAP kinase pathway) in the vascular tissues of obese Zucker rats. |
| 857 | 10512355 | Tyrosine phosphorylation of specific protein kinase C isoenzymes participates in insulin stimulation of glucose transport in primary cultures of rat skeletal muscle. |
| 858 | 10512355 | Several reports indicate that protein kinase C (PKC) plays a role in insulin-induced glucose transport in certain cells. |
| 859 | 10512355 | Insulin translocated GLUT3 and GLUT4 without affecting GLUT1. |
| 860 | 10512355 | In contrast, TPA translocated GLUT1 and GLUT3 without affecting GLUT4. |
| 861 | 10512355 | Insulin translocated and tyrosine phosphorylated and activated PKC-beta2 and -zeta; these effects were blocked by phosphatidylinositol 3-kinase (PI3K) inhibitors. |
| 862 | 10512355 | TPA translocated and activated PKC-alpha, -beta2, and -delta; these effects were not noticeably affected by PI3K inhibitors. |
| 863 | 10512355 | Furthermore, wortmannin significantly inhibited both insulin and TPA effects on GLUT translocation and glucose uptake. |
| 864 | 10512355 | Tyrosine phosphorylation of specific protein kinase C isoenzymes participates in insulin stimulation of glucose transport in primary cultures of rat skeletal muscle. |
| 865 | 10512355 | Several reports indicate that protein kinase C (PKC) plays a role in insulin-induced glucose transport in certain cells. |
| 866 | 10512355 | Insulin translocated GLUT3 and GLUT4 without affecting GLUT1. |
| 867 | 10512355 | In contrast, TPA translocated GLUT1 and GLUT3 without affecting GLUT4. |
| 868 | 10512355 | Insulin translocated and tyrosine phosphorylated and activated PKC-beta2 and -zeta; these effects were blocked by phosphatidylinositol 3-kinase (PI3K) inhibitors. |
| 869 | 10512355 | TPA translocated and activated PKC-alpha, -beta2, and -delta; these effects were not noticeably affected by PI3K inhibitors. |
| 870 | 10512355 | Furthermore, wortmannin significantly inhibited both insulin and TPA effects on GLUT translocation and glucose uptake. |
| 871 | 10531330 | Discordant effects of glucosamine on insulin-stimulated glucose metabolism and phosphatidylinositol 3-kinase activity. |
| 872 | 10531330 | The impact of increased GlcN availability on insulin-stimulated p85/p110 phosphatidylinositol 3-kinase (PI3K) activity in skeletal muscle was examined in relation to GlcN-induced defects in peripheral insulin action. |
| 873 | 10531330 | Primed continuous GlcN infusion (750 micromol/kg bolus; 30 micromol/kg.min) in conscious rats limited both maximal stimulation of muscle PI3K by acute insulin (I) (1 unit/kg) bolus (I + GlcN = 1.9-fold versus saline = 3.3-fold above fasting levels; p < 0.01) and chronic activation of PI3K following 3-h euglycemic, hyperinsulinemic (18 milliunits/kg.min) clamp studies (I + GlcN = 1.2-fold versus saline = 2.6-fold stimulation; p < 0.01). |
| 874 | 10531330 | To determine the time course of GlcN-induced defects in insulin-stimulated PI3K activity and peripheral insulin action, GlcN was administered for 30, 60, 90, or 120 min during 2-h euglycemic, hyperinsulinemic clamp studies. |
| 875 | 10531330 | Activation of muscle PI3K by insulin was attenuated following only 30 min of GlcN infusion (GlcN 30 min = 1.5-fold versus saline = 2.5-fold stimulation; p < 0.05). |
| 876 | 10531330 | Thus, increased GlcN availability induced (a) profound and early inhibition of proximal insulin signaling at the level of PI3K and (b) delayed effects on insulin-mediated glucose uptake, yet (c) complete sparing of insulin-mediated glycogen synthase activation. |
| 877 | 10531330 | Discordant effects of glucosamine on insulin-stimulated glucose metabolism and phosphatidylinositol 3-kinase activity. |
| 878 | 10531330 | The impact of increased GlcN availability on insulin-stimulated p85/p110 phosphatidylinositol 3-kinase (PI3K) activity in skeletal muscle was examined in relation to GlcN-induced defects in peripheral insulin action. |
| 879 | 10531330 | Primed continuous GlcN infusion (750 micromol/kg bolus; 30 micromol/kg.min) in conscious rats limited both maximal stimulation of muscle PI3K by acute insulin (I) (1 unit/kg) bolus (I + GlcN = 1.9-fold versus saline = 3.3-fold above fasting levels; p < 0.01) and chronic activation of PI3K following 3-h euglycemic, hyperinsulinemic (18 milliunits/kg.min) clamp studies (I + GlcN = 1.2-fold versus saline = 2.6-fold stimulation; p < 0.01). |
| 880 | 10531330 | To determine the time course of GlcN-induced defects in insulin-stimulated PI3K activity and peripheral insulin action, GlcN was administered for 30, 60, 90, or 120 min during 2-h euglycemic, hyperinsulinemic clamp studies. |
| 881 | 10531330 | Activation of muscle PI3K by insulin was attenuated following only 30 min of GlcN infusion (GlcN 30 min = 1.5-fold versus saline = 2.5-fold stimulation; p < 0.05). |
| 882 | 10531330 | Thus, increased GlcN availability induced (a) profound and early inhibition of proximal insulin signaling at the level of PI3K and (b) delayed effects on insulin-mediated glucose uptake, yet (c) complete sparing of insulin-mediated glycogen synthase activation. |
| 883 | 10531330 | Discordant effects of glucosamine on insulin-stimulated glucose metabolism and phosphatidylinositol 3-kinase activity. |
| 884 | 10531330 | The impact of increased GlcN availability on insulin-stimulated p85/p110 phosphatidylinositol 3-kinase (PI3K) activity in skeletal muscle was examined in relation to GlcN-induced defects in peripheral insulin action. |
| 885 | 10531330 | Primed continuous GlcN infusion (750 micromol/kg bolus; 30 micromol/kg.min) in conscious rats limited both maximal stimulation of muscle PI3K by acute insulin (I) (1 unit/kg) bolus (I + GlcN = 1.9-fold versus saline = 3.3-fold above fasting levels; p < 0.01) and chronic activation of PI3K following 3-h euglycemic, hyperinsulinemic (18 milliunits/kg.min) clamp studies (I + GlcN = 1.2-fold versus saline = 2.6-fold stimulation; p < 0.01). |
| 886 | 10531330 | To determine the time course of GlcN-induced defects in insulin-stimulated PI3K activity and peripheral insulin action, GlcN was administered for 30, 60, 90, or 120 min during 2-h euglycemic, hyperinsulinemic clamp studies. |
| 887 | 10531330 | Activation of muscle PI3K by insulin was attenuated following only 30 min of GlcN infusion (GlcN 30 min = 1.5-fold versus saline = 2.5-fold stimulation; p < 0.05). |
| 888 | 10531330 | Thus, increased GlcN availability induced (a) profound and early inhibition of proximal insulin signaling at the level of PI3K and (b) delayed effects on insulin-mediated glucose uptake, yet (c) complete sparing of insulin-mediated glycogen synthase activation. |
| 889 | 10531330 | Discordant effects of glucosamine on insulin-stimulated glucose metabolism and phosphatidylinositol 3-kinase activity. |
| 890 | 10531330 | The impact of increased GlcN availability on insulin-stimulated p85/p110 phosphatidylinositol 3-kinase (PI3K) activity in skeletal muscle was examined in relation to GlcN-induced defects in peripheral insulin action. |
| 891 | 10531330 | Primed continuous GlcN infusion (750 micromol/kg bolus; 30 micromol/kg.min) in conscious rats limited both maximal stimulation of muscle PI3K by acute insulin (I) (1 unit/kg) bolus (I + GlcN = 1.9-fold versus saline = 3.3-fold above fasting levels; p < 0.01) and chronic activation of PI3K following 3-h euglycemic, hyperinsulinemic (18 milliunits/kg.min) clamp studies (I + GlcN = 1.2-fold versus saline = 2.6-fold stimulation; p < 0.01). |
| 892 | 10531330 | To determine the time course of GlcN-induced defects in insulin-stimulated PI3K activity and peripheral insulin action, GlcN was administered for 30, 60, 90, or 120 min during 2-h euglycemic, hyperinsulinemic clamp studies. |
| 893 | 10531330 | Activation of muscle PI3K by insulin was attenuated following only 30 min of GlcN infusion (GlcN 30 min = 1.5-fold versus saline = 2.5-fold stimulation; p < 0.05). |
| 894 | 10531330 | Thus, increased GlcN availability induced (a) profound and early inhibition of proximal insulin signaling at the level of PI3K and (b) delayed effects on insulin-mediated glucose uptake, yet (c) complete sparing of insulin-mediated glycogen synthase activation. |
| 895 | 10531330 | Discordant effects of glucosamine on insulin-stimulated glucose metabolism and phosphatidylinositol 3-kinase activity. |
| 896 | 10531330 | The impact of increased GlcN availability on insulin-stimulated p85/p110 phosphatidylinositol 3-kinase (PI3K) activity in skeletal muscle was examined in relation to GlcN-induced defects in peripheral insulin action. |
| 897 | 10531330 | Primed continuous GlcN infusion (750 micromol/kg bolus; 30 micromol/kg.min) in conscious rats limited both maximal stimulation of muscle PI3K by acute insulin (I) (1 unit/kg) bolus (I + GlcN = 1.9-fold versus saline = 3.3-fold above fasting levels; p < 0.01) and chronic activation of PI3K following 3-h euglycemic, hyperinsulinemic (18 milliunits/kg.min) clamp studies (I + GlcN = 1.2-fold versus saline = 2.6-fold stimulation; p < 0.01). |
| 898 | 10531330 | To determine the time course of GlcN-induced defects in insulin-stimulated PI3K activity and peripheral insulin action, GlcN was administered for 30, 60, 90, or 120 min during 2-h euglycemic, hyperinsulinemic clamp studies. |
| 899 | 10531330 | Activation of muscle PI3K by insulin was attenuated following only 30 min of GlcN infusion (GlcN 30 min = 1.5-fold versus saline = 2.5-fold stimulation; p < 0.05). |
| 900 | 10531330 | Thus, increased GlcN availability induced (a) profound and early inhibition of proximal insulin signaling at the level of PI3K and (b) delayed effects on insulin-mediated glucose uptake, yet (c) complete sparing of insulin-mediated glycogen synthase activation. |
| 901 | 10531330 | Discordant effects of glucosamine on insulin-stimulated glucose metabolism and phosphatidylinositol 3-kinase activity. |
| 902 | 10531330 | The impact of increased GlcN availability on insulin-stimulated p85/p110 phosphatidylinositol 3-kinase (PI3K) activity in skeletal muscle was examined in relation to GlcN-induced defects in peripheral insulin action. |
| 903 | 10531330 | Primed continuous GlcN infusion (750 micromol/kg bolus; 30 micromol/kg.min) in conscious rats limited both maximal stimulation of muscle PI3K by acute insulin (I) (1 unit/kg) bolus (I + GlcN = 1.9-fold versus saline = 3.3-fold above fasting levels; p < 0.01) and chronic activation of PI3K following 3-h euglycemic, hyperinsulinemic (18 milliunits/kg.min) clamp studies (I + GlcN = 1.2-fold versus saline = 2.6-fold stimulation; p < 0.01). |
| 904 | 10531330 | To determine the time course of GlcN-induced defects in insulin-stimulated PI3K activity and peripheral insulin action, GlcN was administered for 30, 60, 90, or 120 min during 2-h euglycemic, hyperinsulinemic clamp studies. |
| 905 | 10531330 | Activation of muscle PI3K by insulin was attenuated following only 30 min of GlcN infusion (GlcN 30 min = 1.5-fold versus saline = 2.5-fold stimulation; p < 0.05). |
| 906 | 10531330 | Thus, increased GlcN availability induced (a) profound and early inhibition of proximal insulin signaling at the level of PI3K and (b) delayed effects on insulin-mediated glucose uptake, yet (c) complete sparing of insulin-mediated glycogen synthase activation. |
| 907 | 10545524 | Insulin, exercise, and the combination of exercise plus insulin did not increase IR tyrosine phosphorylation or phosphatidylinositol 3-kinase activity in MIRKO muscle. |
| 908 | 10545524 | In contrast, insulin alone produced a small activation of Akt and glycogen synthase kinase-3 in MIRKO mice, and prior exercise markedly enhanced this insulin effect. |
| 909 | 10574950 | Insulin-induced tyrosine phosphorylation of the insulin receptor, insulin receptor substrate 1 (IRS-1), and IRS-2 was reduced by prestimulation of beta(3)-adrenergic receptors (CL316243). |
| 910 | 10574950 | Similarly, insulin-induced IRS-1-associated and phosphotyrosine-associated phosphatidylinositol 3-kinase (PI 3-kinase) activity, but not IRS-2-associated PI 3-kinase activity, was reduced by beta(3)-adrenergic prestimulation. |
| 911 | 10574950 | Furthermore, insulin-stimulated activation of Akt, but not mitogen-activated protein kinase, was diminished. |
| 912 | 10574950 | Furthermore inhibition of protein kinase C restored the beta(3)-receptor-mediated reductions in insulin-induced IRS-1 tyrosine phosphorylation and IRS-1-associated PI 3-kinase activity. |
| 913 | 10574950 | This interaction is protein kinase A-dependent and, at least in part, protein kinase C-dependent, and could play an important role in the pathogenesis of insulin resistance associated with sympathetic overactivity and regulation of brown fat metabolism. |
| 914 | 10579924 | It appears that Akt/PKB lies in the crossroads of multiple cellular signaling pathways and acts as a transducer of many functions initiated by growth factor receptors that activate phosphatidylinositol 3-kinase (PI 3-kinase). |
| 915 | 10579924 | In addition, the recent discovery of the tumor suppressor PTEN as an antagonist of PI 3-kinase and Akt/PKB kinase activity suggests that Akt/PKB is a critical factor in the genesis of cancer. |
| 916 | 10585879 | Role of janus kinase-2 in insulin-mediated phosphorylation and inactivation of protein phosphatase-2A and its impact on upstream insulin signalling components. |
| 917 | 10585879 | Our recent studies indicate that insulin rapidly inactivates serine/threonine protein phosphatase-2A (PP-2A) by increasing tyrosine phosphorylation on the catalytic subunit. |
| 918 | 10585879 | The exact mechanism of PP-2A inactivation by insulin in vivo is unclear. |
| 919 | 10585879 | In this study we investigated the potential role of JAK-2 in insulin-mediated tyrosine phosphorylation and inactivation of PP-2A using the rat skeletal muscle cell line L6. |
| 920 | 10585879 | Co-immunoprecipitation studies revealed that PP-2A is associated with JAK-2 in the basal state. |
| 921 | 10585879 | Insulin treatment did not alter JAK-2 association with PP-2A, but did increase JAK-2-mediated tyrosine phosphorylation of the PP-2A catalytic subunit and therefore inhibited PP-2A enzymic activity. |
| 922 | 10585879 | Furthermore, PP-2A is associated with phosphoinositide 3-kinase (PI-3K) in the basal state and insulin treatment increases the catalytic activity of PI-3K bound to PP-2A. |
| 923 | 10585879 | Pretreatment with AG-490, a specific JAK-2 inhibitor, and SpcAMP, a cAMP agonist, prevented the insulin-mediated increase in (i) JAK-2 kinase activity, (ii) PP-2A tyrosine phosphorylation, (iii) PP-2A inactivation and restored the enzyme activity to control levels, and (iv) PP-2A and JAK-2-associated PI-3K activity. |
| 924 | 10585879 | These observations, together with the fact that insulin rapidly activates JAK-2 in L6 cells, and that this is accompanied by an increase in tyrosine phosphorylation of PP-2A in JAK-2 immunoprecipitates, suggest that insulin controls the activation status of PP-2A by tyrosine phosphorylation via JAK-2. |
| 925 | 10585879 | PP-2A inactivation may result in an amplification of insulin-generated signals at the level of PI-3K. |
| 926 | 10585879 | Role of janus kinase-2 in insulin-mediated phosphorylation and inactivation of protein phosphatase-2A and its impact on upstream insulin signalling components. |
| 927 | 10585879 | Our recent studies indicate that insulin rapidly inactivates serine/threonine protein phosphatase-2A (PP-2A) by increasing tyrosine phosphorylation on the catalytic subunit. |
| 928 | 10585879 | The exact mechanism of PP-2A inactivation by insulin in vivo is unclear. |
| 929 | 10585879 | In this study we investigated the potential role of JAK-2 in insulin-mediated tyrosine phosphorylation and inactivation of PP-2A using the rat skeletal muscle cell line L6. |
| 930 | 10585879 | Co-immunoprecipitation studies revealed that PP-2A is associated with JAK-2 in the basal state. |
| 931 | 10585879 | Insulin treatment did not alter JAK-2 association with PP-2A, but did increase JAK-2-mediated tyrosine phosphorylation of the PP-2A catalytic subunit and therefore inhibited PP-2A enzymic activity. |
| 932 | 10585879 | Furthermore, PP-2A is associated with phosphoinositide 3-kinase (PI-3K) in the basal state and insulin treatment increases the catalytic activity of PI-3K bound to PP-2A. |
| 933 | 10585879 | Pretreatment with AG-490, a specific JAK-2 inhibitor, and SpcAMP, a cAMP agonist, prevented the insulin-mediated increase in (i) JAK-2 kinase activity, (ii) PP-2A tyrosine phosphorylation, (iii) PP-2A inactivation and restored the enzyme activity to control levels, and (iv) PP-2A and JAK-2-associated PI-3K activity. |
| 934 | 10585879 | These observations, together with the fact that insulin rapidly activates JAK-2 in L6 cells, and that this is accompanied by an increase in tyrosine phosphorylation of PP-2A in JAK-2 immunoprecipitates, suggest that insulin controls the activation status of PP-2A by tyrosine phosphorylation via JAK-2. |
| 935 | 10585879 | PP-2A inactivation may result in an amplification of insulin-generated signals at the level of PI-3K. |
| 936 | 10585879 | Role of janus kinase-2 in insulin-mediated phosphorylation and inactivation of protein phosphatase-2A and its impact on upstream insulin signalling components. |
| 937 | 10585879 | Our recent studies indicate that insulin rapidly inactivates serine/threonine protein phosphatase-2A (PP-2A) by increasing tyrosine phosphorylation on the catalytic subunit. |
| 938 | 10585879 | The exact mechanism of PP-2A inactivation by insulin in vivo is unclear. |
| 939 | 10585879 | In this study we investigated the potential role of JAK-2 in insulin-mediated tyrosine phosphorylation and inactivation of PP-2A using the rat skeletal muscle cell line L6. |
| 940 | 10585879 | Co-immunoprecipitation studies revealed that PP-2A is associated with JAK-2 in the basal state. |
| 941 | 10585879 | Insulin treatment did not alter JAK-2 association with PP-2A, but did increase JAK-2-mediated tyrosine phosphorylation of the PP-2A catalytic subunit and therefore inhibited PP-2A enzymic activity. |
| 942 | 10585879 | Furthermore, PP-2A is associated with phosphoinositide 3-kinase (PI-3K) in the basal state and insulin treatment increases the catalytic activity of PI-3K bound to PP-2A. |
| 943 | 10585879 | Pretreatment with AG-490, a specific JAK-2 inhibitor, and SpcAMP, a cAMP agonist, prevented the insulin-mediated increase in (i) JAK-2 kinase activity, (ii) PP-2A tyrosine phosphorylation, (iii) PP-2A inactivation and restored the enzyme activity to control levels, and (iv) PP-2A and JAK-2-associated PI-3K activity. |
| 944 | 10585879 | These observations, together with the fact that insulin rapidly activates JAK-2 in L6 cells, and that this is accompanied by an increase in tyrosine phosphorylation of PP-2A in JAK-2 immunoprecipitates, suggest that insulin controls the activation status of PP-2A by tyrosine phosphorylation via JAK-2. |
| 945 | 10585879 | PP-2A inactivation may result in an amplification of insulin-generated signals at the level of PI-3K. |
| 946 | 10644515 | High glucose and insulin inhibit VSMC MKP-1 expression by blocking iNOS via p38 MAPK activation. |
| 947 | 10644515 | Our laboratory has recently demonstrated a role for the phosphatidylinositol 3-kinase-mediated inducible NO synthase (iNOS) signaling pathway in acute regulation of insulin-induced mitogen-activated protein phosphatase-1 (MKP-1) expression in primary cultures of rat aortic vascular smooth muscle cells (VSMCs) (N. |
| 948 | 10644515 | We now show that prolonged treatment of VSMCs with 100 nM insulin and high glucose (25 mM) for 12-24 h, to mimic hyperinsulinemia and hyperglycemia, completely blocked MKP-1 mRNA and protein expression in response to subsequent acute insulin treatment. |
| 949 | 10644515 | To understand the mechanism of insulin resistance induced by high glucose and insulin, we studied the regulation of iNOS protein induction in these cells. |
| 950 | 10644515 | Both high glucose and chronic insulin treatment caused a marked impairment of iNOS induction in response to acute insulin. |
| 951 | 10644515 | Blocking of signaling via the p38 mitogen-activated protein kinase (MAPK) pathway by prior treatment for 1 h with SB-203580, a synthetic p38 MAPK inhibitor, completely prevented the inhibition of iNOS induced by high glucose and insulin and restored MKP-1 induction to levels observed with acute insulin treatment. |
| 952 | 10644515 | Furthermore, high glucose and chronic insulin treatment caused sustained p38 MAPK activation. |
| 953 | 10644515 | We conclude 1) that chronic insulin and high glucose-induced insulin resistance is accompanied by marked reductions in both iNOS and MKP-1 inductions due to p38 MAPK activation that leads to excessive cell growth and 2) that p38 MAPK/extracellular signal-regulated kinase pathways regulate iNOS induction, thereby controlling MKP-1 expression, which in turn inactivates MAPKs as a feedback mechanism and inhibits cell growth. |
| 954 | 10668913 | Preincubation of cardiomyocytes with the phosphatidylinositol 3-kinase inhibitor wortmannin completely abolished the effects of insulin and thioctic acid, whereas gamma-linolenic acid selectively blocked the effect of this compound. |
| 955 | 10668913 | These data show that thioctic acid mimics insulin action by activating the signalling cascade at or before the level of phosphatidylinositol 3-kinase. |
| 956 | 10668913 | Preincubation of cardiomyocytes with the phosphatidylinositol 3-kinase inhibitor wortmannin completely abolished the effects of insulin and thioctic acid, whereas gamma-linolenic acid selectively blocked the effect of this compound. |
| 957 | 10668913 | These data show that thioctic acid mimics insulin action by activating the signalling cascade at or before the level of phosphatidylinositol 3-kinase. |
| 958 | 10675357 | Insulin resistance differentially affects the PI 3-kinase- and MAP kinase-mediated signaling in human muscle. |
| 959 | 10675357 | Insulin stimulation of the phosphatidylinositol 3-kinase (PI 3-kinase) pathway, as measured by phosphorylation of the insulin receptor and IRS-1 and by IRS protein association with p85 and with PI 3-kinase, was dramatically reduced in obese nondiabetics and virtually absent in type 2 diabetic patients. |
| 960 | 10675357 | Insulin stimulation of the MAP kinase pathway was normal in obese and diabetic subjects. |
| 961 | 10675357 | Insulin stimulation of glucose-disposal correlated with association of p85 with IRS-1. |
| 962 | 10675357 | Exercise 24 hours before the euglycemic clamp increased phosphorylation of insulin receptor and IRS-1 in obese and diabetic subjects but did not increase glucose uptake or PI 3-kinase association with IRS-1 upon insulin stimulation. |
| 963 | 10675357 | Thus, insulin resistance differentially affects the PI 3-kinase and MAP kinase signaling pathways, and insulin-stimulated IRS-1-association with PI 3-kinase defines a key step in insulin resistance. |
| 964 | 10688912 | Selective interaction between leptin and insulin signaling pathways in a hepatic cell line. |
| 965 | 10688912 | Leptin is a 16-kDa hormone secreted by adipocytes and plays an important role in control of feeding behavior and energy expenditure. |
| 966 | 10688912 | In obesity, circulating levels of leptin and insulin are high because of the presence of increased body fat mass and insulin resistance. |
| 967 | 10688912 | Recent reports have suggested that leptin can act through some of the components of the insulin signaling cascade, such as insulin receptor substrates (IRS-1 and IRS-2), phosphatidylinositol 3-kinase (PI 3-kinase), and mitogen-activated protein kinase, and can modify insulin-induced changes in gene expression in vitro and in vivo. |
| 968 | 10688912 | Well differentiated hepatoma cells (Fao) possess both the long and short forms of the leptin receptor and respond to leptin with a stimulation of c-fos gene expression. |
| 969 | 10688912 | In Fao cells, leptin alone had no effects on the insulin signaling pathway, but leptin pretreatment transiently enhanced insulin-induced tyrosine phosphorylation and PI 3-kinase binding to IRS-1, while producing an inhibition of tyrosine phosphorylation and PI 3-kinase binding to IRS-2. |
| 970 | 10688912 | Leptin alone also induced serine phosphorylation of Akt and glycogen synthase kinase 3 but to a lesser extent than insulin, and the combination of these hormones was not additive. |
| 971 | 10688912 | These results suggest complex interactions between the leptin and insulin signaling pathways that can potentially lead to differential modification of the metabolic and mitotic effects of insulin exerted through IRS-1 and IRS-2 and the downstream kinases that they activate. |
| 972 | 10698715 | Initial signalling events of insulin action, including receptor kinase activation, the tyrosine phosphorylation of insulin receptor substrate (IRS)-1 and IRS-2 and the recruitment of PI-3K to IRS-1 and IRS-2, were found not to be involved in contraction-mediated signalling. |
| 973 | 10707556 | The insulin-activated pathway is the phosphatidylinositol 3-kinase pathway in the endothelial cells and MAP kinase pathway in the VSMC. |
| 974 | 10722680 | Both of these abnormalities were associated with defects in insulin activation of insulin receptor substrate-1 and -2-associated phosphatidylinositol 3-kinase activity and a 2-fold increase in muscle and liver triglyceride content. |
| 975 | 10722680 | In conclusion, these results suggest that the development of insulin resistance in type 2 diabetes may be due to alterations in the partitioning of fat between the adipocyte and muscle/liver leading to accumulation of triglyceride in the latter tissues with subsequent impairment of insulin signaling and action. |
| 976 | 10726921 | In muscle obtained during clamp studies prior to vanadium therapy, insulin stimulated the tyrosine phosphorylation of the insulin receptor, insulin receptor substrate-1 (IRS-1), and Shc proteins by 2- to 3-fold, while phosphatidylinositol 3-kinase (PI 3-kinase) activity associated with IRS-1 increased 4.7-fold during insulin stimulation (P = .02). |
| 977 | 10726921 | Following vanadium, there was a consistent trend for increased basal levels of insulin receptor, Shc, and IRS-1 protein tyrosine phosphorylation and IRS-1-associated PI 3-kinase, but no further increase with insulin. |
| 978 | 10726921 | Vanadyl modifies proteins in human skeletal muscle involved in early insulin signaling, including basal insulin receptor and substrate tyrosine phosphorylation and activation of PI 3-kinase, and is not additive or synergistic with insulin at these steps. |
| 979 | 10744689 | Phosphorylation of PDE3B by phosphatidylinositol 3-kinase associated with the insulin receptor. |
| 980 | 10744689 | Phosphatidylinositol 3-kinase mediates several actions of insulin including its antilipolytic effect. |
| 981 | 10744689 | This effect is elicited by the insulin-stimulated serine phosphorylation and activation of cGMP-inhibited phosphodiesterase (PDE3B). |
| 982 | 10744689 | In human adipocytes, we found that insulin differentially stimulated phosphatidylinositol 3-kinase activity; the lipid kinase activity was associated with IRS-1, whereas the serine kinase activity was associated with the insulin receptor and phosphorylated a number of proteins including p85, p110, and a 135-kDa protein identified as PDE3B. |
| 983 | 10744689 | Phosphorylation of PDE3B by phosphatidylinositol 3-kinase associated with the insulin receptor. |
| 984 | 10744689 | Phosphatidylinositol 3-kinase mediates several actions of insulin including its antilipolytic effect. |
| 985 | 10744689 | This effect is elicited by the insulin-stimulated serine phosphorylation and activation of cGMP-inhibited phosphodiesterase (PDE3B). |
| 986 | 10744689 | In human adipocytes, we found that insulin differentially stimulated phosphatidylinositol 3-kinase activity; the lipid kinase activity was associated with IRS-1, whereas the serine kinase activity was associated with the insulin receptor and phosphorylated a number of proteins including p85, p110, and a 135-kDa protein identified as PDE3B. |
| 987 | 10744689 | Phosphorylation of PDE3B by phosphatidylinositol 3-kinase associated with the insulin receptor. |
| 988 | 10744689 | Phosphatidylinositol 3-kinase mediates several actions of insulin including its antilipolytic effect. |
| 989 | 10744689 | This effect is elicited by the insulin-stimulated serine phosphorylation and activation of cGMP-inhibited phosphodiesterase (PDE3B). |
| 990 | 10744689 | In human adipocytes, we found that insulin differentially stimulated phosphatidylinositol 3-kinase activity; the lipid kinase activity was associated with IRS-1, whereas the serine kinase activity was associated with the insulin receptor and phosphorylated a number of proteins including p85, p110, and a 135-kDa protein identified as PDE3B. |
| 991 | 10751417 | Overexpression of protein-tyrosine phosphatase-1B in adipocytes inhibits insulin-stimulated phosphoinositide 3-kinase activity without altering glucose transport or Akt/Protein kinase B activation. |
| 992 | 10751417 | Previous studies suggested that protein-tyrosine phosphatase 1B (PTP1B) antagonizes insulin action by catalyzing dephosphorylation of the insulin receptor (IR) and/or other key proteins in the insulin signaling pathway. |
| 993 | 10751417 | In adipose tissue and muscle of obese humans and rodents, PTP1B expression is increased, which led to the hypothesis that PTP1B plays a role in the pathogenesis of insulin resistance. |
| 994 | 10751417 | Consistent with this, mice in which the PTP1B gene was disrupted exhibit increased insulin sensitivity. |
| 995 | 10751417 | To test whether increased expression of PTP1B in an insulin-sensitive cell type could contribute to insulin resistance, we overexpressed wild-type PTP1B in 3T3L1 adipocytes using adenovirus-mediated gene delivery. |
| 996 | 10751417 | Compared with control cells, cells expressing high levels of PTP1B showed a 50-60% decrease in maximally insulin-stimulated tyrosyl phosphorylation of IR and insulin receptor substrate-1 (IRS-1) and phosphoinositide 3-kinase (PI3K) activity associated with IRS-1 or with phosphotyrosine. |
| 997 | 10751417 | Phosphorylation of p42 and p44 MAP kinase (MAPK) was reduced approximately 32%. |
| 998 | 10751417 | Overexpression of PTP1B had no effect on basal, submaximally or maximally (100 nm) insulin-stimulated glucose transport or on the EC(50) for transport. |
| 999 | 10751417 | Our results suggest that: 1) insulin stimulation of glucose transport in adipocytes requires </=45% of maximal tyrosyl phosphorylation of IR or IRS-1 and <50% of maximal activation of PI3K, 2) a novel PI3K-independent pathway may play a role in insulin-induced glucose transport in adipocytes, and 3) overexpression of PTP1B alone in adipocytes does not impair glucose transport. |
| 1000 | 10751417 | Overexpression of protein-tyrosine phosphatase-1B in adipocytes inhibits insulin-stimulated phosphoinositide 3-kinase activity without altering glucose transport or Akt/Protein kinase B activation. |
| 1001 | 10751417 | Previous studies suggested that protein-tyrosine phosphatase 1B (PTP1B) antagonizes insulin action by catalyzing dephosphorylation of the insulin receptor (IR) and/or other key proteins in the insulin signaling pathway. |
| 1002 | 10751417 | In adipose tissue and muscle of obese humans and rodents, PTP1B expression is increased, which led to the hypothesis that PTP1B plays a role in the pathogenesis of insulin resistance. |
| 1003 | 10751417 | Consistent with this, mice in which the PTP1B gene was disrupted exhibit increased insulin sensitivity. |
| 1004 | 10751417 | To test whether increased expression of PTP1B in an insulin-sensitive cell type could contribute to insulin resistance, we overexpressed wild-type PTP1B in 3T3L1 adipocytes using adenovirus-mediated gene delivery. |
| 1005 | 10751417 | Compared with control cells, cells expressing high levels of PTP1B showed a 50-60% decrease in maximally insulin-stimulated tyrosyl phosphorylation of IR and insulin receptor substrate-1 (IRS-1) and phosphoinositide 3-kinase (PI3K) activity associated with IRS-1 or with phosphotyrosine. |
| 1006 | 10751417 | Phosphorylation of p42 and p44 MAP kinase (MAPK) was reduced approximately 32%. |
| 1007 | 10751417 | Overexpression of PTP1B had no effect on basal, submaximally or maximally (100 nm) insulin-stimulated glucose transport or on the EC(50) for transport. |
| 1008 | 10751417 | Our results suggest that: 1) insulin stimulation of glucose transport in adipocytes requires </=45% of maximal tyrosyl phosphorylation of IR or IRS-1 and <50% of maximal activation of PI3K, 2) a novel PI3K-independent pathway may play a role in insulin-induced glucose transport in adipocytes, and 3) overexpression of PTP1B alone in adipocytes does not impair glucose transport. |
| 1009 | 10768097 | Regulation of gene expression during severe caloric restriction: lack of induction of p85 alpha phosphatidylinositol 3-kinase mRNA in skeletal muscle of patients with type II (non-insulin-dependent) diabetes mellitus. |
| 1010 | 10801879 | Coimmunoprecipitation experiments demonstrated insulin-dependent binding of dIRS to phosphatidylinositol 3-kinase and SHP2. |
| 1011 | 10801879 | However, we did not detect interactions with Grb2, SHC, or phospholipase C-gamma. |
| 1012 | 10811851 | Expression of an IRS-1 mutant (IRS-1Deltap85) lacking the binding site for the p85 subunit of phosphatidylinositol 3-kinase (PI3K) also restored insulin sensitivity, although PI3K is known to play a crucial role in insulin's metabolic responses. |
| 1013 | 10811851 | Protein kinase B (PKB) activity in liver was decreased in null mice compared with the wild-type and the null mice expressing IRS-1 or IRS-1Deltap85. |
| 1014 | 10811851 | In primary hepatocytes isolated from null mice, expression of IRS-1 enhanced both PI3K and PKB activities, but expression of IRS-1Deltap85 enhanced only PKB. |
| 1015 | 10811851 | These data suggest that PKB in liver plays a pivotal role in systemic glucose homeostasis and that PKB activation might be sufficient for reducing insulin resistance even without full activation of PI3K. |
| 1016 | 10811851 | Expression of an IRS-1 mutant (IRS-1Deltap85) lacking the binding site for the p85 subunit of phosphatidylinositol 3-kinase (PI3K) also restored insulin sensitivity, although PI3K is known to play a crucial role in insulin's metabolic responses. |
| 1017 | 10811851 | Protein kinase B (PKB) activity in liver was decreased in null mice compared with the wild-type and the null mice expressing IRS-1 or IRS-1Deltap85. |
| 1018 | 10811851 | In primary hepatocytes isolated from null mice, expression of IRS-1 enhanced both PI3K and PKB activities, but expression of IRS-1Deltap85 enhanced only PKB. |
| 1019 | 10811851 | These data suggest that PKB in liver plays a pivotal role in systemic glucose homeostasis and that PKB activation might be sufficient for reducing insulin resistance even without full activation of PI3K. |
| 1020 | 10811851 | Expression of an IRS-1 mutant (IRS-1Deltap85) lacking the binding site for the p85 subunit of phosphatidylinositol 3-kinase (PI3K) also restored insulin sensitivity, although PI3K is known to play a crucial role in insulin's metabolic responses. |
| 1021 | 10811851 | Protein kinase B (PKB) activity in liver was decreased in null mice compared with the wild-type and the null mice expressing IRS-1 or IRS-1Deltap85. |
| 1022 | 10811851 | In primary hepatocytes isolated from null mice, expression of IRS-1 enhanced both PI3K and PKB activities, but expression of IRS-1Deltap85 enhanced only PKB. |
| 1023 | 10811851 | These data suggest that PKB in liver plays a pivotal role in systemic glucose homeostasis and that PKB activation might be sufficient for reducing insulin resistance even without full activation of PI3K. |
| 1024 | 10813377 | In vascular smooth muscle cells (VSMCs), insulin transduces a mitogenic signal that is dependent on the ERK1/2 MAP kinases. |
| 1025 | 10813377 | TRO at I and 10 microM had no significant effect on insulin-stimulated ERK1/2 activity. |
| 1026 | 10813377 | At 20 microM, however, TRO modestly enhanced insulin-stimulated ERK1/2 activity by 1.5-fold. |
| 1027 | 10813377 | TRO at 1-20 microM potently inhibited insulin-stimulated, ERK1/2-dependent Elk-1 transcription factor activity. |
| 1028 | 10813377 | Neither early steps in insulin signaling nor the phosphatidylinositol 3-kinase (PI3K) branch of this pathway were affected by TRO, because it had no effect on IRS-1 phosphorylation, PI3K/IRS-1 association, or Akt phosphorylation. |
| 1029 | 10813377 | In summary, these data show that TRO inhibits mitogenic signaling by insulin at a point distal of ERK1/2 activation, potentially by a PPARgamma-mediated inhibition of ERK-dependent phosphorylation and activation of nuclear transcription factors that regulate cell growth. |
| 1030 | 10829028 | Activation of serum response factor in the depolarization induction of Egr-1 transcription in pancreatic islet beta-cells. |
| 1031 | 10829028 | Pharmacological inhibition of the Egr-1 induction by H89 (48%) and calmidazolium (35%), but not by mitogen-activated protein kinase/extracellular signal-regulated kinase kinase 1 and 2 or phosphatidylinositol 3-kinase inhibitors, implied that protein kinase A and Ca(2+)/calmodulin pathways are involved. |
| 1032 | 10829028 | Depolarization activation of 5XSRE-LUC and serum response factor (SRF)-GAL4 constructs, along with activation of SRF-GAL4 by co-transfection with constitutively active calmodulin kinase IV and protein kinase A, and binding of Ser(103)-phosphorylated SRF in nuclear extracts, indicated that the SRE.SRF complexes contribute to the Ca(2+)-mediated transcriptional regulation of Egr-1. |
| 1033 | 10842663 | We demonstrate that fatty acids and amino acids inhibit early post-receptor steps in insulin action, including tyrosine phosphorylation of insulin receptor substrate (IRS) proteins and activation of phosphatidylinositol 3-kinase (PI3-kinase), both in vitro and in several in vivo models. |
| 1034 | 10842663 | Similarly, activation of the hexosamine pathway by infusion of glucosamine also reduces insulin-stimulated phosphorylation of IRS proteins, activation of PI3-kinase, and activation of glycogen synthase. |
| 1035 | 10866052 | In these cells, insulin stimulation of glucose uptake, glycogen synthesis, insulin receptor (IR) kinase activity, and insulin receptor substrate 1-associated phosphatidylinositol 3-kinase (PI 3-kinase) activity were measured. |
| 1036 | 10866052 | Furthermore, insulin activation of protein kinase B (PKB) was compared with immunoblotting of serine residues at position 473. |
| 1037 | 10866052 | Insulin stimulation (1 nmol/l) of IR kinase and PI 3-kinase were maximal within 5 min (approximately 8- and 5-fold over basal, respectively), and insulin activation of PKB was maximal within 15 min (approximately 3.5-fold over basal). |
| 1038 | 10868937 | Inhibitory effect of IGF-I on type 2 nitric oxide synthase expression in Ins-1 cells and protection against activation-dependent apoptosis: involvement of phosphatidylinositol 3-kinase. |
| 1039 | 10868937 | Challenge of Ins-1 cells, a rat beta-pancreatic cell line, with lipopolysaccharide (LPS) and interferon-gamma (IFN-gamma) promoted the expression of type 2 nitric oxide synthase (NOS-2) in a cooperative way. |
| 1040 | 10868937 | Treatment of Ins-1 cells with IGF-I significantly inhibited the expression of NOS-2, especially at subsaturating concentrations of LPS and IFN-gamma. |
| 1041 | 10868937 | The inhibitory effect of IGF-I on NOS-2 expression was abrogated when cells were incubated with wortmannin or LY294002, two inhibitors of phosphatidylinositol 3-kinase. |
| 1042 | 10868937 | Transient expression of the p110 subunit of phosphatidylinositol 3-kinase impaired the LPS and IFN-gamma-dependent NOS-2 promoter activity in cells transfected with a 1-kb fragment corresponding to the 5'-flanking region of the NOS-2 gene. |
| 1043 | 10868937 | However, expression of a dominant negative form of p85 abolished the inhibitory action of IGF-I on the NOS-2 promoter activity. |
| 1044 | 10868937 | However, in activated cells treated with N-[3-(aminomethyl)benzyl]acetamidine, a specific NOS-2 inhibitor, IGF-I completely abolished the NO-independent apoptosis. |
| 1045 | 10868937 | Inhibitory effect of IGF-I on type 2 nitric oxide synthase expression in Ins-1 cells and protection against activation-dependent apoptosis: involvement of phosphatidylinositol 3-kinase. |
| 1046 | 10868937 | Challenge of Ins-1 cells, a rat beta-pancreatic cell line, with lipopolysaccharide (LPS) and interferon-gamma (IFN-gamma) promoted the expression of type 2 nitric oxide synthase (NOS-2) in a cooperative way. |
| 1047 | 10868937 | Treatment of Ins-1 cells with IGF-I significantly inhibited the expression of NOS-2, especially at subsaturating concentrations of LPS and IFN-gamma. |
| 1048 | 10868937 | The inhibitory effect of IGF-I on NOS-2 expression was abrogated when cells were incubated with wortmannin or LY294002, two inhibitors of phosphatidylinositol 3-kinase. |
| 1049 | 10868937 | Transient expression of the p110 subunit of phosphatidylinositol 3-kinase impaired the LPS and IFN-gamma-dependent NOS-2 promoter activity in cells transfected with a 1-kb fragment corresponding to the 5'-flanking region of the NOS-2 gene. |
| 1050 | 10868937 | However, expression of a dominant negative form of p85 abolished the inhibitory action of IGF-I on the NOS-2 promoter activity. |
| 1051 | 10868937 | However, in activated cells treated with N-[3-(aminomethyl)benzyl]acetamidine, a specific NOS-2 inhibitor, IGF-I completely abolished the NO-independent apoptosis. |
| 1052 | 10868937 | Inhibitory effect of IGF-I on type 2 nitric oxide synthase expression in Ins-1 cells and protection against activation-dependent apoptosis: involvement of phosphatidylinositol 3-kinase. |
| 1053 | 10868937 | Challenge of Ins-1 cells, a rat beta-pancreatic cell line, with lipopolysaccharide (LPS) and interferon-gamma (IFN-gamma) promoted the expression of type 2 nitric oxide synthase (NOS-2) in a cooperative way. |
| 1054 | 10868937 | Treatment of Ins-1 cells with IGF-I significantly inhibited the expression of NOS-2, especially at subsaturating concentrations of LPS and IFN-gamma. |
| 1055 | 10868937 | The inhibitory effect of IGF-I on NOS-2 expression was abrogated when cells were incubated with wortmannin or LY294002, two inhibitors of phosphatidylinositol 3-kinase. |
| 1056 | 10868937 | Transient expression of the p110 subunit of phosphatidylinositol 3-kinase impaired the LPS and IFN-gamma-dependent NOS-2 promoter activity in cells transfected with a 1-kb fragment corresponding to the 5'-flanking region of the NOS-2 gene. |
| 1057 | 10868937 | However, expression of a dominant negative form of p85 abolished the inhibitory action of IGF-I on the NOS-2 promoter activity. |
| 1058 | 10868937 | However, in activated cells treated with N-[3-(aminomethyl)benzyl]acetamidine, a specific NOS-2 inhibitor, IGF-I completely abolished the NO-independent apoptosis. |
| 1059 | 10868952 | However, prior exercise did not result in a greater or more rapid increase in insulin-induced receptor tyrosine kinase (IRTK) activity (t1/2 = 50 min), serine phosphorylation of Akt (t1/2 = 1-2 min), or serine phosphorylation of glycogen synthase kinase-3 (GSK-3) (t1/2 = 1-2 min) or in a larger or more rapid decrease in GSK-3 activity (t1/2 = 3-8 min). |
| 1060 | 10868952 | We conclude the following: 1) physiological hyperinsulinemia induces sustained activation of insulin-signaling molecules in human skeletal muscle; 2) the more distal insulin-signaling components (Akt, GSK-3) are activated much more rapidly than the proximal signaling molecules (IRTK as well as insulin receptor substrate 1 and phosphatidylinositol 3-kinase [Wojtaszewski et al., Diabetes 46:1775-1781, 1997]); and 3) prior exercise increases insulin stimulation of both glucose uptake and glycogen synthase activity in the absence of an upregulation of signaling events in human skeletal muscle. |
| 1061 | 10905496 | Divergent regulation of Akt1 and Akt2 isoforms in insulin target tissues of obese Zucker rats. |
| 1062 | 10905496 | To determine whether impaired Akt (protein kinase B or rac) activation contributes to insulin resistance in vivo, we examined the expression, phosphorylation, and kinase activities of Akt1 and Akt2 isoforms in insulin target tissues of insulin-resistant obese Zucker rats. |
| 1063 | 10905496 | In lean rats, insulin (10 U/kg i.v. x 2.5 min) stimulated Akt1 activity 6.2-, 8.8-, and 4.4-fold and Akt2 activity 5.4-, 9.3-, and 1.8-fold in muscle, liver, and adipose tissue, respectively. |
| 1064 | 10905496 | In obese rats, insulin-stimulated Akt1 activity decreased 30% in muscle and 21% in adipose tissue but increased 37% in liver compared with lean littermates. |
| 1065 | 10905496 | Insulin-stimulated Akt2 activity decreased 29% in muscle and 37% in liver but increased 24% in adipose tissue. |
| 1066 | 10905496 | Akt2 protein levels were reduced 56% in muscle and 35% in liver of obese rats, but Akt1 expression was unaltered. |
| 1067 | 10905496 | Phosphoinositide 3-kinase (PI3K) activity associated with insulin receptor substrate (IRS)-1 or phosphotyrosine was reduced 67-86% in tissues of obese rats because of lower IRS-1 protein levels and reduced insulin receptor and IRS-1 phosphorylation. |
| 1068 | 10905496 | In adipose tissue of obese rats, in spite of an 86% reduction in insulin-stimulated PI3K activity, activation of Akt2 was increased. |
| 1069 | 10905496 | Maximal insulin-stimulated (100 nmol/l) glucose transport was reduced 70% in isolated adipocytes, with a rightward shift in the insulin dose response for transport and for Akt1 stimulation but normal sensitivity for Akt2. |
| 1070 | 10905496 | These findings suggest that PI3K-dependent effects on glucose transport in adipocytes are not mediated primarily by Akt2. |
| 1071 | 10905496 | Akt1 and Akt2 activations by insulin have a similar time course and are maximal by 2.5 min in adipocytes of both lean and obese rats. |
| 1072 | 10905496 | We conclude that 1) activation of Akt1 and Akt2 in vivo is much less impaired than activation of PI3K in this insulin-resistant state, and 2) the mechanisms for divergent alterations in insulin action on Akt1 and Akt2 activities in tissues of insulin-resistant obese rats involve tissue- and isoform-specific changes in both expression and activation. |
| 1073 | 10905496 | Divergent regulation of Akt1 and Akt2 isoforms in insulin target tissues of obese Zucker rats. |
| 1074 | 10905496 | To determine whether impaired Akt (protein kinase B or rac) activation contributes to insulin resistance in vivo, we examined the expression, phosphorylation, and kinase activities of Akt1 and Akt2 isoforms in insulin target tissues of insulin-resistant obese Zucker rats. |
| 1075 | 10905496 | In lean rats, insulin (10 U/kg i.v. x 2.5 min) stimulated Akt1 activity 6.2-, 8.8-, and 4.4-fold and Akt2 activity 5.4-, 9.3-, and 1.8-fold in muscle, liver, and adipose tissue, respectively. |
| 1076 | 10905496 | In obese rats, insulin-stimulated Akt1 activity decreased 30% in muscle and 21% in adipose tissue but increased 37% in liver compared with lean littermates. |
| 1077 | 10905496 | Insulin-stimulated Akt2 activity decreased 29% in muscle and 37% in liver but increased 24% in adipose tissue. |
| 1078 | 10905496 | Akt2 protein levels were reduced 56% in muscle and 35% in liver of obese rats, but Akt1 expression was unaltered. |
| 1079 | 10905496 | Phosphoinositide 3-kinase (PI3K) activity associated with insulin receptor substrate (IRS)-1 or phosphotyrosine was reduced 67-86% in tissues of obese rats because of lower IRS-1 protein levels and reduced insulin receptor and IRS-1 phosphorylation. |
| 1080 | 10905496 | In adipose tissue of obese rats, in spite of an 86% reduction in insulin-stimulated PI3K activity, activation of Akt2 was increased. |
| 1081 | 10905496 | Maximal insulin-stimulated (100 nmol/l) glucose transport was reduced 70% in isolated adipocytes, with a rightward shift in the insulin dose response for transport and for Akt1 stimulation but normal sensitivity for Akt2. |
| 1082 | 10905496 | These findings suggest that PI3K-dependent effects on glucose transport in adipocytes are not mediated primarily by Akt2. |
| 1083 | 10905496 | Akt1 and Akt2 activations by insulin have a similar time course and are maximal by 2.5 min in adipocytes of both lean and obese rats. |
| 1084 | 10905496 | We conclude that 1) activation of Akt1 and Akt2 in vivo is much less impaired than activation of PI3K in this insulin-resistant state, and 2) the mechanisms for divergent alterations in insulin action on Akt1 and Akt2 activities in tissues of insulin-resistant obese rats involve tissue- and isoform-specific changes in both expression and activation. |
| 1085 | 10905496 | Divergent regulation of Akt1 and Akt2 isoforms in insulin target tissues of obese Zucker rats. |
| 1086 | 10905496 | To determine whether impaired Akt (protein kinase B or rac) activation contributes to insulin resistance in vivo, we examined the expression, phosphorylation, and kinase activities of Akt1 and Akt2 isoforms in insulin target tissues of insulin-resistant obese Zucker rats. |
| 1087 | 10905496 | In lean rats, insulin (10 U/kg i.v. x 2.5 min) stimulated Akt1 activity 6.2-, 8.8-, and 4.4-fold and Akt2 activity 5.4-, 9.3-, and 1.8-fold in muscle, liver, and adipose tissue, respectively. |
| 1088 | 10905496 | In obese rats, insulin-stimulated Akt1 activity decreased 30% in muscle and 21% in adipose tissue but increased 37% in liver compared with lean littermates. |
| 1089 | 10905496 | Insulin-stimulated Akt2 activity decreased 29% in muscle and 37% in liver but increased 24% in adipose tissue. |
| 1090 | 10905496 | Akt2 protein levels were reduced 56% in muscle and 35% in liver of obese rats, but Akt1 expression was unaltered. |
| 1091 | 10905496 | Phosphoinositide 3-kinase (PI3K) activity associated with insulin receptor substrate (IRS)-1 or phosphotyrosine was reduced 67-86% in tissues of obese rats because of lower IRS-1 protein levels and reduced insulin receptor and IRS-1 phosphorylation. |
| 1092 | 10905496 | In adipose tissue of obese rats, in spite of an 86% reduction in insulin-stimulated PI3K activity, activation of Akt2 was increased. |
| 1093 | 10905496 | Maximal insulin-stimulated (100 nmol/l) glucose transport was reduced 70% in isolated adipocytes, with a rightward shift in the insulin dose response for transport and for Akt1 stimulation but normal sensitivity for Akt2. |
| 1094 | 10905496 | These findings suggest that PI3K-dependent effects on glucose transport in adipocytes are not mediated primarily by Akt2. |
| 1095 | 10905496 | Akt1 and Akt2 activations by insulin have a similar time course and are maximal by 2.5 min in adipocytes of both lean and obese rats. |
| 1096 | 10905496 | We conclude that 1) activation of Akt1 and Akt2 in vivo is much less impaired than activation of PI3K in this insulin-resistant state, and 2) the mechanisms for divergent alterations in insulin action on Akt1 and Akt2 activities in tissues of insulin-resistant obese rats involve tissue- and isoform-specific changes in both expression and activation. |
| 1097 | 10905496 | Divergent regulation of Akt1 and Akt2 isoforms in insulin target tissues of obese Zucker rats. |
| 1098 | 10905496 | To determine whether impaired Akt (protein kinase B or rac) activation contributes to insulin resistance in vivo, we examined the expression, phosphorylation, and kinase activities of Akt1 and Akt2 isoforms in insulin target tissues of insulin-resistant obese Zucker rats. |
| 1099 | 10905496 | In lean rats, insulin (10 U/kg i.v. x 2.5 min) stimulated Akt1 activity 6.2-, 8.8-, and 4.4-fold and Akt2 activity 5.4-, 9.3-, and 1.8-fold in muscle, liver, and adipose tissue, respectively. |
| 1100 | 10905496 | In obese rats, insulin-stimulated Akt1 activity decreased 30% in muscle and 21% in adipose tissue but increased 37% in liver compared with lean littermates. |
| 1101 | 10905496 | Insulin-stimulated Akt2 activity decreased 29% in muscle and 37% in liver but increased 24% in adipose tissue. |
| 1102 | 10905496 | Akt2 protein levels were reduced 56% in muscle and 35% in liver of obese rats, but Akt1 expression was unaltered. |
| 1103 | 10905496 | Phosphoinositide 3-kinase (PI3K) activity associated with insulin receptor substrate (IRS)-1 or phosphotyrosine was reduced 67-86% in tissues of obese rats because of lower IRS-1 protein levels and reduced insulin receptor and IRS-1 phosphorylation. |
| 1104 | 10905496 | In adipose tissue of obese rats, in spite of an 86% reduction in insulin-stimulated PI3K activity, activation of Akt2 was increased. |
| 1105 | 10905496 | Maximal insulin-stimulated (100 nmol/l) glucose transport was reduced 70% in isolated adipocytes, with a rightward shift in the insulin dose response for transport and for Akt1 stimulation but normal sensitivity for Akt2. |
| 1106 | 10905496 | These findings suggest that PI3K-dependent effects on glucose transport in adipocytes are not mediated primarily by Akt2. |
| 1107 | 10905496 | Akt1 and Akt2 activations by insulin have a similar time course and are maximal by 2.5 min in adipocytes of both lean and obese rats. |
| 1108 | 10905496 | We conclude that 1) activation of Akt1 and Akt2 in vivo is much less impaired than activation of PI3K in this insulin-resistant state, and 2) the mechanisms for divergent alterations in insulin action on Akt1 and Akt2 activities in tissues of insulin-resistant obese rats involve tissue- and isoform-specific changes in both expression and activation. |
| 1109 | 10909976 | It has previously been shown that Wortmannin, a phosphatidylinositol 3-kinase inhibitor, inhibits glucose transport activated by insulin but not by ischemia, suggesting the importance of an activating mechanism that bypasses the insulin signal. |
| 1110 | 10909975 | Expression of insulin receptor substrate 1, phosphatidylinositol 3-kinase, protein kinase B, and glycogen synthase was normal in the relative cultures with impaired insulin responsiveness. |
| 1111 | 10909984 | Induction of endothelin-1 expression by glucose: an effect of protein kinase C activation. |
| 1112 | 10909984 | Elevation of glucose, but not mannitol, from 5.5 to 25 mmol/l for 3 days increased membranous protein kinase C (PKC) activities and ET-1 mRNA in parallel levels by 2-fold in BREC and BRPC. |
| 1113 | 10909984 | Glucose-induced ET-1 overexpression was inhibited by a general PKC inhibitor, GF109203X, and a mitogen-activated protein kinase kinase inhibitor, PD98059, but not by wortmannin, a phosphatidylinositol 3-kinase inhibitor. |
| 1114 | 10909984 | Overexpression of PKC-beta1 and -delta isoforms but not PKC-zeta isoform by adenovirus vectors containing the respective cDNA enhanced in parallel PKC activities, proteins, and basal and glucose-induced ET-1 mRNA expression by at least 2-fold. |
| 1115 | 10909984 | These results showed that enhanced ET-1 expression induced by hyperglycemia in diabetes is partly due to activation of PKC-beta and -delta isoforms, suggesting that inhibition of these PKC isoforms may prevent early changes in diabetic retinopathy and neuropathy. |
| 1116 | 10926840 | Regulation of GLUT5, GLUT2 and intestinal brush-border fructose absorption by the extracellular signal-regulated kinase, p38 mitogen-activated kinase and phosphatidylinositol 3-kinase intracellular signalling pathways: implications for adaptation to diabetes. |
| 1117 | 10926840 | We have investigated the role of the extracellular signal-regulated kinase (ERK), p38 and phosphatidylinositol 3-kinase (PI 3-kinase) pathways in the regulation of intestinal fructose transport. |
| 1118 | 10926840 | Transport was mediated by both GLUT5 and GLUT2. |
| 1119 | 10926840 | In general, GLUT2 levels increased up to 4-fold within minutes and with only minimal changes in GLUT5 or SGLT1 levels, demonstrating that GLUT2 trafficks by a rapid trafficking pathway distinct from that of GLUT5 and SGLT1. |
| 1120 | 10926840 | It is concluded that there is extensive cross-talk between the ERK, p38 and PI 3-kinase pathways in their control of brush-border fructose transport by modulation of both the levels and intrinsic activities of GLUT5 and GLUT2. |
| 1121 | 10926840 | Regulation of GLUT5, GLUT2 and intestinal brush-border fructose absorption by the extracellular signal-regulated kinase, p38 mitogen-activated kinase and phosphatidylinositol 3-kinase intracellular signalling pathways: implications for adaptation to diabetes. |
| 1122 | 10926840 | We have investigated the role of the extracellular signal-regulated kinase (ERK), p38 and phosphatidylinositol 3-kinase (PI 3-kinase) pathways in the regulation of intestinal fructose transport. |
| 1123 | 10926840 | Transport was mediated by both GLUT5 and GLUT2. |
| 1124 | 10926840 | In general, GLUT2 levels increased up to 4-fold within minutes and with only minimal changes in GLUT5 or SGLT1 levels, demonstrating that GLUT2 trafficks by a rapid trafficking pathway distinct from that of GLUT5 and SGLT1. |
| 1125 | 10926840 | It is concluded that there is extensive cross-talk between the ERK, p38 and PI 3-kinase pathways in their control of brush-border fructose transport by modulation of both the levels and intrinsic activities of GLUT5 and GLUT2. |
| 1126 | 10940305 | The glucagon-like peptide-2 receptor mediates direct inhibition of cellular apoptosis via a cAMP-dependent protein kinase-independent pathway. |
| 1127 | 10940305 | Because GLP-2 decreases mortality and reduces intestinal apoptosis in rodents after experimental injury, we examined whether GLP-2R signaling directly modifies the cellular response to external injury. |
| 1128 | 10940305 | We show here that activation of GLP-2R signaling inhibits cycloheximide-induced apoptosis in baby hamster kidney fibroblasts expressing a transfected GLP-2 receptor. |
| 1129 | 10940305 | GLP-2 reduced DNA fragmentation and improved cell survival, in association with reduced activation of caspase-3 and decreased poly(ADP-ribose) polymerase cleavage and reduced caspase-8 and caspase-9-like activities. |
| 1130 | 10940305 | Both GLP-2 and forskolin reduced mitochondrial cytochrome c release and decreased the cycloheximide-induced cleavage of caspase-3 in the presence or absence of the PKA inhibitor H-89. |
| 1131 | 10940305 | These findings provide evidence that signaling through G protein-coupled receptors of the glucagon superfamily is directly linked to regulation of apoptosis and suggest the existence of a cAMP-dependent protein kinase-, phosphatidylinositol 3-kinase-, and mitogen-activated protein kinase-independent pathway coupling GLP-2R signaling to caspase inhibition and cell survival. |
| 1132 | 10976915 | Regulation of myosin-bound protein phosphatase by insulin in vascular smooth muscle cells: evaluation of the role of Rho kinase and phosphatidylinositol-3-kinase-dependent signaling pathways. |
| 1133 | 10976915 | Insulin-mediated MBP activation was accompanied by a rapid time-dependent reduction in the phosphorylation state of the myosin-bound regulatory subunit (MBS) of MBP. |
| 1134 | 10976915 | The decrease observed in MBS phosphorylation was due to insulin-induced inhibition of Rho kinase activity. |
| 1135 | 10976915 | Insulin also prevented a thrombin-mediated increase in Rho kinase activation and abolished the thrombin-induced increase in MBS phosphorylation and MBP inactivation. |
| 1136 | 10976915 | These data are consistent with the notion that insulin inactivates Rho kinase and decreases MBS phosphorylation to activate MBP in VSMCs. |
| 1137 | 10976915 | Furthermore, treatment with synthetic inhibitors of phosphatidylinositol-3 kinase (PI3-kinase), nitric oxide synthase (NOS), and cyclic guanosine monophosphate (cGMP) all blocked insulin's effect on MBP activation. |
| 1138 | 10976915 | We conclude that insulin stimulates MBP via its regulatory subunit, MBS partly by inactivating Rho kinase and stimulating NO/cGMP signaling via PI3-kinase as part of a complex signaling network that controls 20-kDa myosin light chain (MLC20) phosphorylation and VSMC contraction. |
| 1139 | 10976915 | Regulation of myosin-bound protein phosphatase by insulin in vascular smooth muscle cells: evaluation of the role of Rho kinase and phosphatidylinositol-3-kinase-dependent signaling pathways. |
| 1140 | 10976915 | Insulin-mediated MBP activation was accompanied by a rapid time-dependent reduction in the phosphorylation state of the myosin-bound regulatory subunit (MBS) of MBP. |
| 1141 | 10976915 | The decrease observed in MBS phosphorylation was due to insulin-induced inhibition of Rho kinase activity. |
| 1142 | 10976915 | Insulin also prevented a thrombin-mediated increase in Rho kinase activation and abolished the thrombin-induced increase in MBS phosphorylation and MBP inactivation. |
| 1143 | 10976915 | These data are consistent with the notion that insulin inactivates Rho kinase and decreases MBS phosphorylation to activate MBP in VSMCs. |
| 1144 | 10976915 | Furthermore, treatment with synthetic inhibitors of phosphatidylinositol-3 kinase (PI3-kinase), nitric oxide synthase (NOS), and cyclic guanosine monophosphate (cGMP) all blocked insulin's effect on MBP activation. |
| 1145 | 10976915 | We conclude that insulin stimulates MBP via its regulatory subunit, MBS partly by inactivating Rho kinase and stimulating NO/cGMP signaling via PI3-kinase as part of a complex signaling network that controls 20-kDa myosin light chain (MLC20) phosphorylation and VSMC contraction. |
| 1146 | 10997626 | Cardiac insulin resistance is associated with an impaired recruitment of phosphatidylinositol 3-kinase to GLUT4 vesicles. |
| 1147 | 11007772 | Expression of constitutively active phosphatidylinositol 3-kinase inhibits activation of caspase 3 and apoptosis of cardiac muscle cells. |
| 1148 | 11007772 | Recent studies showed that insulin-like growth factor I (IGF-I) inhibits apoptosis of cardiac muscle cells and improves myocardial function in experimental heart failure. |
| 1149 | 11007772 | This study was carried out to elucidate the role of phosphatidylinositol 3-kinase (PI 3-kinase) in the anti-apoptotic actions of IGF-I in cardiomyocytes and to explore whether expression of constitutively active PI 3-kinase can inhibit apoptosis in cardiomyocytes. |
| 1150 | 11007772 | Transduction of cardiomyocytes with constitutively active PI 3-kinase specifically lead to serine phosphorylation of Akt, whereas phosphorylation of IGF-I receptor, IRS1/2 and p44/42 mitogen-activated protein kinase were not increased. |
| 1151 | 11007772 | These findings indicate the existence of an IGF-I receptor-PI 3-kinase-caspase 3 pathway in cardiomyocytes that plays an important role in the anti-apoptotic actions of IGF-I in heart. |
| 1152 | 11007772 | Expression of constitutively active phosphatidylinositol 3-kinase inhibits activation of caspase 3 and apoptosis of cardiac muscle cells. |
| 1153 | 11007772 | Recent studies showed that insulin-like growth factor I (IGF-I) inhibits apoptosis of cardiac muscle cells and improves myocardial function in experimental heart failure. |
| 1154 | 11007772 | This study was carried out to elucidate the role of phosphatidylinositol 3-kinase (PI 3-kinase) in the anti-apoptotic actions of IGF-I in cardiomyocytes and to explore whether expression of constitutively active PI 3-kinase can inhibit apoptosis in cardiomyocytes. |
| 1155 | 11007772 | Transduction of cardiomyocytes with constitutively active PI 3-kinase specifically lead to serine phosphorylation of Akt, whereas phosphorylation of IGF-I receptor, IRS1/2 and p44/42 mitogen-activated protein kinase were not increased. |
| 1156 | 11007772 | These findings indicate the existence of an IGF-I receptor-PI 3-kinase-caspase 3 pathway in cardiomyocytes that plays an important role in the anti-apoptotic actions of IGF-I in heart. |
| 1157 | 11016454 | On the other hand, dexamethasone treatment did not alter the amount of GLUT4 protein in total cell lysates but decreased the insulin-stimulated GLUT4 translocation to the plasma membrane, which possibly caused decreased insulin-stimulated glucose uptake. |
| 1158 | 11016454 | To investigate whether the reduced IRS-1 content is involved in insulin resistance, IRS-1 was overexpressed in dexamethasone-treated 3T3-L1 adipocytes using an adenovirus transfection system. |
| 1159 | 11016454 | Despite protein expression and phosphorylation levels of IRS-1 being normalized, insulin-induced 2-deoxy-D-[3H]glucose uptake impaired by dexamethasone showed no significant improvement. |
| 1160 | 11016454 | Subsequently, we examined the effect of dexamethasone on the glucose uptake increase induced by overexpression of GLUT2-tagged p110alpha, constitutively active Akt (myristoylated Akt), oxidative stress (30 mU glucose oxidase for 2 h), 2 mmol/l 5-aminoimidazole-4-carboxamide ribonucleoside for 30 min, and osmotic shock (600 mmol/l sorbitol for 30 min). |
| 1161 | 11016454 | Thus, in conclusion, the GLUT1 decrease may be involved in the dexamethasone-induced decrease in basal glucose transport activity, and the mechanism of dexamethasone-induced insulin resistance in glucose transport activity (rather than the inhibition of phosphatidylinositol 3-kinase activation resulting from a decreased IRS-1 content) is likely to underlie impaired glucose transporter regulation. |
| 1162 | 11016454 | On the other hand, dexamethasone treatment did not alter the amount of GLUT4 protein in total cell lysates but decreased the insulin-stimulated GLUT4 translocation to the plasma membrane, which possibly caused decreased insulin-stimulated glucose uptake. |
| 1163 | 11016454 | To investigate whether the reduced IRS-1 content is involved in insulin resistance, IRS-1 was overexpressed in dexamethasone-treated 3T3-L1 adipocytes using an adenovirus transfection system. |
| 1164 | 11016454 | Despite protein expression and phosphorylation levels of IRS-1 being normalized, insulin-induced 2-deoxy-D-[3H]glucose uptake impaired by dexamethasone showed no significant improvement. |
| 1165 | 11016454 | Subsequently, we examined the effect of dexamethasone on the glucose uptake increase induced by overexpression of GLUT2-tagged p110alpha, constitutively active Akt (myristoylated Akt), oxidative stress (30 mU glucose oxidase for 2 h), 2 mmol/l 5-aminoimidazole-4-carboxamide ribonucleoside for 30 min, and osmotic shock (600 mmol/l sorbitol for 30 min). |
| 1166 | 11016454 | Thus, in conclusion, the GLUT1 decrease may be involved in the dexamethasone-induced decrease in basal glucose transport activity, and the mechanism of dexamethasone-induced insulin resistance in glucose transport activity (rather than the inhibition of phosphatidylinositol 3-kinase activation resulting from a decreased IRS-1 content) is likely to underlie impaired glucose transporter regulation. |
| 1167 | 11016459 | Gene encoding the catalytic subunit p110beta of human phosphatidylinositol 3-kinase: cloning, genomic structure, and screening for variants in patients with type 2 diabetes. |
| 1168 | 11016459 | Our results may indicate that the catalytic subunit p110beta of PI 3-kinase plays such a fundamental role in the insulin-signaling pathway that structural variants are not likely to exist in that gene. |
| 1169 | 11016459 | The importance of the polymorphisms in the proximal/5' region of the p110beta gene for insulin signaling remains to be determined. |
| 1170 | 11018037 | Vascular endothelial growth factor induces expression of connective tissue growth factor via KDR, Flt1, and phosphatidylinositol 3-kinase-akt-dependent pathways in retinal vascular cells. |
| 1171 | 11018037 | Since connective tissue growth factor (CTGF) is a potent mitogen for fibrosis, extracellular matrix production, and angiogenesis, we have studied the effects and mechanism by which vascular endothelial growth factor (VEGF) regulates CTGF gene expression in retinal capillary cells. |
| 1172 | 11018037 | In our study, VEGF increased CTGF mRNA levels in a time- and concentration-dependent manner in bovine retinal endothelial cells and pericytes, without the need of new protein synthesis and without altering mRNA stability. |
| 1173 | 11018037 | VEGF activated the tyrosine receptor phosphorylation of KDR and Flt1 and increased the binding of phosphatidylinositol 3-kinase (PI3-kinase) p85 subunit to KDR and Flt1, both of which could mediate CTGF gene induction. |
| 1174 | 11018037 | VEGF-induced CTGF expression was mediated primarily by PI3-kinase activation, whereas PKC and ERK pathways made only minimal contributions. |
| 1175 | 11018037 | Furthermore, overexpression of constitutive active Akt was sufficient to induce CTGF gene expression, and inhibition of Akt activation by overexpressing dominant negative mutant of Akt abolished the VEGF-induced CTGF expression. |
| 1176 | 11018037 | These data suggest that VEGF can increase CTGF gene expression in bovine retinal capillary cells via KDR or Flt receptors and the activation of PI3-kinase-Akt pathway independently of PKC or Ras-ERK pathway, possibly inducing the fibrosis observed in retinal neovascular diseases. |
| 1177 | 11018037 | Vascular endothelial growth factor induces expression of connective tissue growth factor via KDR, Flt1, and phosphatidylinositol 3-kinase-akt-dependent pathways in retinal vascular cells. |
| 1178 | 11018037 | Since connective tissue growth factor (CTGF) is a potent mitogen for fibrosis, extracellular matrix production, and angiogenesis, we have studied the effects and mechanism by which vascular endothelial growth factor (VEGF) regulates CTGF gene expression in retinal capillary cells. |
| 1179 | 11018037 | In our study, VEGF increased CTGF mRNA levels in a time- and concentration-dependent manner in bovine retinal endothelial cells and pericytes, without the need of new protein synthesis and without altering mRNA stability. |
| 1180 | 11018037 | VEGF activated the tyrosine receptor phosphorylation of KDR and Flt1 and increased the binding of phosphatidylinositol 3-kinase (PI3-kinase) p85 subunit to KDR and Flt1, both of which could mediate CTGF gene induction. |
| 1181 | 11018037 | VEGF-induced CTGF expression was mediated primarily by PI3-kinase activation, whereas PKC and ERK pathways made only minimal contributions. |
| 1182 | 11018037 | Furthermore, overexpression of constitutive active Akt was sufficient to induce CTGF gene expression, and inhibition of Akt activation by overexpressing dominant negative mutant of Akt abolished the VEGF-induced CTGF expression. |
| 1183 | 11018037 | These data suggest that VEGF can increase CTGF gene expression in bovine retinal capillary cells via KDR or Flt receptors and the activation of PI3-kinase-Akt pathway independently of PKC or Ras-ERK pathway, possibly inducing the fibrosis observed in retinal neovascular diseases. |
| 1184 | 11027274 | The gene for the p85alpha regulatory subunit yields three splicing variants, p85alpha, AS53/p55alpha, and p50alpha. |
| 1185 | 11027274 | To determine if these regulatory subunits differ in their effects on enzyme activity and signal transduction from insulin receptor substrate (IRS) proteins under physiological conditions, we expressed each regulatory subunit in fully differentiated L6 myotubes using adenovirus-mediated gene transfer with or without coexpression of the p110alpha catalytic subunit. |
| 1186 | 11027274 | Insulin stimulation of two kinases downstream from PI-3 kinase, Akt and p70 S6 kinase (p70(S6K)), was decreased in cells expressing p85alpha or AS53 but not in cells expressing p50alpha. |
| 1187 | 11027274 | Similar inhibition of PI 3-kinase, Akt, and p70(S6K) was observed, even when p110alpha was coexpressed with p85alpha or AS53. |
| 1188 | 11027274 | The gene for the p85alpha regulatory subunit yields three splicing variants, p85alpha, AS53/p55alpha, and p50alpha. |
| 1189 | 11027274 | To determine if these regulatory subunits differ in their effects on enzyme activity and signal transduction from insulin receptor substrate (IRS) proteins under physiological conditions, we expressed each regulatory subunit in fully differentiated L6 myotubes using adenovirus-mediated gene transfer with or without coexpression of the p110alpha catalytic subunit. |
| 1190 | 11027274 | Insulin stimulation of two kinases downstream from PI-3 kinase, Akt and p70 S6 kinase (p70(S6K)), was decreased in cells expressing p85alpha or AS53 but not in cells expressing p50alpha. |
| 1191 | 11027274 | Similar inhibition of PI 3-kinase, Akt, and p70(S6K) was observed, even when p110alpha was coexpressed with p85alpha or AS53. |
| 1192 | 11053255 | Leptin promotes invasiveness of kidney and colonic epithelial cells via phosphoinositide 3-kinase-, rho-, and rac-dependent signaling pathways. |
| 1193 | 11053255 | First, leptin potently (EC50 = 10-30 ng/ml) induces invasion of collagen gels by premalignant familial adenomatous colonic cells PC/AA/C1 and nontumorigenic MDCK kidney epithelial cells, their src-transformed counterparts, and the human adenocarcinoma colonic cells LoVo and HCT-8/S11. |
| 1194 | 11053255 | Leptin-induced invasion was effectively blocked by pharmacological inhibitors of several downstream signaling pathways involved in cell transformation, namely, JAK2 tyrosine kinase (AG490), phosphoinositide PI3'-kinase (wortmannin and LY294002), mTOR kinase (rapamycin), and protein kinases C (GF109203X, Gö6976). |
| 1195 | 11053255 | Accordingly, leptin induces transient elevation of the PI3'-kinase lipid products in JAK2 immunoprecipitates prepared from parental MDCK cells. |
| 1196 | 11053255 | The leptin effect on invasion was potentiated by the activated form of the small GTPase RhoA and was abrogated by dominant negative mutants of RhoA, Rac1, and the p110alpha of PI3'-K. |
| 1197 | 11078443 | Sustained activation of insulin receptors internalized in GLUT4 vesicles of insulin-stimulated skeletal muscle. |
| 1198 | 11078443 | We report herein that, in skeletal muscle, in vivo stimulation with insulin induced a rapid internalization of the IR to an insulin-sensitive GLUT4-enriched intracellular membrane fraction. |
| 1199 | 11078443 | In marked contrast with hepatic endosomes or adipocyte low-density microsomes, no IR tyrosine dephosphorylation activity was observed in GLUT4-enriched vesicles isolated from skeletal muscle. |
| 1200 | 11078443 | The activated IR was recovered in immunopurified GLUT4 vesicles after insulin stimulation. |
| 1201 | 11078443 | Insulin also increased tyrosine-phosphorylated insulin receptor substrate 1 and phosphatidylinositol 3-kinase adapter (p85) subunit contents in the intracellular membrane fraction, but these signaling molecules were not directly associated with GLUT4 vesicles. |
| 1202 | 11078443 | We propose that compartmentalization of activated IRs to GLUT4 vesicles may play a role in sustaining insulin signaling at this locus in skeletal muscle. |
| 1203 | 11113178 | Insulin receptor substrate 3 (IRS-3) and IRS-4 impair IRS-1- and IRS-2-mediated signaling. |
| 1204 | 11113178 | To investigate the roles of insulin receptor substrate 3 (IRS-3) and IRS-4 in the insulin-like growth factor 1 (IGF-1) signaling cascade, we introduced these proteins into 3T3 embryonic fibroblast cell lines prepared from wild-type (WT) and IRS-1 knockout (KO) mice by using a retroviral system. |
| 1205 | 11113178 | Following transduction of IRS-3 or IRS-4, the cells showed a significant decrease in IRS-2 mRNA and protein levels without any change in the IRS-1 protein level. |
| 1206 | 11113178 | However, IRS-3- or IRS-4-expressing cells also showed a marked decrease in IRS-1 and IRS-2 phosphorylation compared to the host cells. |
| 1207 | 11113178 | This decrease was accounted for in part by a decrease in the level of IRS-2 protein but occurred with no significant change in the IRS-1 protein level. |
| 1208 | 11113178 | IRS-3- or IRS-4-overexpressing cells showed an increase in basal phosphatidylinositol 3-kinase activity and basal Akt phosphorylation, while the IGF-1-stimulated levels correlated well with total tyrosine phosphorylation level of all IRS proteins in each cell line. |
| 1209 | 11113178 | In the IRS-1 KO cells, the impaired mitogenic response to IGF-1 was reconstituted with IRS-1 to supranormal levels and was returned to almost normal by IRS-2 or IRS-3 but was not improved by overexpression of IRS-4. |
| 1210 | 11113178 | These data suggest that IRS-3 and IRS-4 may act as negative regulators of the IGF-1 signaling pathway by suppressing the function of other IRS proteins at several steps. |
| 1211 | 11113183 | The p90 ribosomal S6 kinase (RSK), a cytosolic substrate for the extracellular signal-regulated kinase (ERK), is involved in transcriptional regulation, and one isoform (RSK2) has been implicated in the activation of glycogen synthase by insulin. |
| 1212 | 11113183 | To determine RSK2 function in vivo, mice lacking a functional rsk2 gene were generated and studied in response to insulin and exercise, two potent stimulators of the ERK cascade in skeletal muscle. |
| 1213 | 11113183 | While insulin and exercise significantly increased ERK phosphorylation in skeletal muscle from both WT and KO mice, the increases were twofold greater in the KO animals. |
| 1214 | 11113183 | The enhanced insulin-stimulated increases in ERK and glycogen synthase activities in KO mice were not associated with higher insulin receptor or with IRS1 tyrosine phosphorylation or with IRS1 binding to phosphatidylinositol 3-kinase. |
| 1215 | 11113183 | However, insulin-stimulated serine phosphorylation of Akt was significantly higher in the KO animals. c-fos mRNA was increased similarly in muscle from WT and KO mice in response to insulin (2. 5-fold) and exercise (15-fold). |
| 1216 | 11113183 | In conclusion, RSK2 likely plays a major role in feedback inhibition of the ERK pathway in skeletal muscle. |
| 1217 | 11113183 | Furthermore, RSK2 is not required for activation of muscle glycogen synthase by insulin but may indirectly modulate muscle glycogen synthase activity and/or glycogen content by other mechanisms, possibly through regulation of Akt. |
| 1218 | 11113183 | RSK2 knockout mice may be a good animal model for the study of Coffin-Lowry syndrome. |
| 1219 | 11113206 | The most widely distributed members of the family of insulin receptor substrate (IRS) proteins are IRS-1 and IRS-2. |
| 1220 | 11113206 | These proteins participate in insulin and insulin-like growth factor 1 signaling, as well as the actions of some cytokines, growth hormone, and prolactin. |
| 1221 | 11113206 | To more precisely define the specific role of IRS-1 in adipocyte biology, we established brown adipocyte cell lines from wild-type and IRS-1 knockout (KO) animals. |
| 1222 | 11113206 | Using differentiation protocols, both with and without insulin, preadipocyte cell lines derived from IRS-1 KO mice exhibited a marked decrease in differentiation and lipid accumulation (10 to 40%) compared to wild-type cells (90 to 100%). |
| 1223 | 11113206 | Furthermore, IRS-1 KO cells showed decreased expression of adipogenic marker proteins, such as peroxisome proliferator-activated receptor gamma (PPARgamma), CCAAT/enhancer-binding protein alpha (C/EBPalpha), fatty acid synthase, uncoupling protein-1, and glucose transporter 4. |
| 1224 | 11113206 | The differentiation deficit in the KO cells could be reversed almost completely by retrovirus-mediated reexpression of IRS-1, PPARgamma, or C/EBPalpha but not the thiazolidinedione troglitazone. |
| 1225 | 11113206 | Phosphatidylinositol 3-kinase (PI 3-kinase) assays performed at various stages of the differentiation process revealed a strong and transient activation in IRS-1, IRS-2, and phosphotyrosine-associated PI 3-kinase in the wild-type cells, whereas the IRS-1 KO cells showed impaired phosphotyrosine-associated PI 3-kinase activation, all of which was associated with IRS-2. |
| 1226 | 11113206 | Thus, IRS-1 appears to be an important mediator of brown adipocyte maturation. |
| 1227 | 11113206 | Furthermore, this signaling molecule appears to exert its unique role in the differentiation process via activation of PI 3-kinase and its downstream target, Akt, and is upstream of the effects of PPARgamma and C/EBPalpha. |
| 1228 | 11120660 | Diversification of cardiac insulin signaling involves the p85 alpha/beta subunits of phosphatidylinositol 3-kinase. |
| 1229 | 11120660 | Ventricular cardiomyocytes and cardiac tissue of lean and genetically obese (fa/fa) Zucker rats were used 1) to study the role of the p85 regulatory subunit isoforms p85 alpha and p85 beta for insulin signaling through the phosphatidylinositol (PI) 3-kinase pathway, and 2) to elucidate the implications of these mechanisms for cardiac insulin resistance. |
| 1230 | 11120660 | Western blot analysis of cardiomyocyte lysates revealed expression of p85 alpha and p85 beta but no detectable amounts of the splice variants of p85 alpha. |
| 1231 | 11120660 | Essentially no p85 alpha subunit of PI 3-kinase was found to be associated with insulin receptor substrate (IRS)-1 or IRS-2 in basal and insulin-stimulated (5 min) cardiomyocytes. |
| 1232 | 11120660 | Instead, insulin produced a twofold increase in p85 beta associated with IRS-1, leading to a three- to fourfold increase in p85 beta-associated PI 3-kinase activity. |
| 1233 | 11120660 | In GLUT-4-containing vesicles, an increased abundance (3.7 +/- 0.7-fold over basal) of p85 alpha was observed after insulin stimulation of lean animals, with no significant effect in the obese group. |
| 1234 | 11120660 | No p85 beta could be detected in GLUT-4-containing vesicles. |
| 1235 | 11120660 | We conclude that, in the heart, p85 alpha recruits PI 3-kinase activity to GLUT-4 vesicles, whereas p85 beta represents the main regulator of IRS-1- and IRS-2-mediated PI 3-kinase activation. |
| 1236 | 11120660 | Furthermore, multiple defects of PI 3-kinase activation, involving both the p85 alpha and the p85 beta adaptor subunits, may contribute to cardiac insulin resistance. |
| 1237 | 11124266 | In Caenorhabditis elegans, an insulin-like signaling pathway to phosphatidylinositol 3-kinase (PI 3-kinase) and AKT negatively regulates the activity of DAF-16, a Forkhead transcription factor. |
| 1238 | 11124266 | We show that in mammalian cells, C. elegans DAF-16 is a direct target of AKT and that AKT phosphorylation generates 14-3-3 binding sites and regulates the nuclear/cytoplasmic distribution of DAF-16 as previously shown for its mammalian homologs FKHR and FKHRL1. |
| 1239 | 11124266 | In vitro, interaction of AKT- phosphorylated DAF-16 with 14-3-3 prevents DAF-16 binding to its target site in the insulin-like growth factor binding protein-1 gene, the insulin response element. |
| 1240 | 11124266 | In HepG2 cells, insulin signaling to PI 3-kinase/AKT inhibits the ability of a GAL4 DNA binding domain/DAF-16 fusion protein to activate transcription via the insulin-like growth factor binding protein-1-insulin response element, but not the GAL4 DNA binding site, which suggests that insulin inhibits the interaction of DAF-16 with its cognate DNA site. |
| 1241 | 11124266 | Elimination of the DAF-16/1433 association by mutation of the AKT/14-3-3 sites in DAF-16, prevents 14-3-3 inhibition of DAF-16 DNA binding and insulin inhibition of DAF-16 function. |
| 1242 | 11147570 | (II) The underlying molecular mechanisms seemed to rely on beta cells on a sulfonylurea receptor protein, SURX, associated with the ATP-sensitive potassium channel (K(ATP)) and different from SUR1 for glibenclamide, and in muscle and adipose cells on: (a) the increased production of diacylglycerol and activation of protein kinase C; (b) the enhanced expression of glucose transporter isoforms; and (c) the insulin receptor-independent activation of the insulin receptor substrate/phosphatidylinositol-3-kinase pathway. |
| 1243 | 11171554 | Defects in insulin signal transduction through the insulin-receptor substrate-1/phosphatidylinositol 3-kinase pathway is associated with reduced insulin-stimulated glucose transport activity in skeletal muscle from Type II diabetic patients. |
| 1244 | 11171554 | Glucose transport, the rate limiting step in glucose metabolism, is mediated by glucose transporter 4 (GLUT4) translocation and can be activated in skeletal muscle by two separate and distinct signaling pathways; one stimulated by insulin and the second by muscle contractions. |
| 1245 | 11171610 | The aim of this study was to investigate the possibility that this deterioration of glucose tolerance is associated with changes in adipocyte insulin action. |
| 1246 | 11171610 | These changes in insulin action were not related to altered expression of insulin receptors or insulin receptor tyrosine phosphorylation; however, they were associated with reduced phosphatidylinositol 3-kinase and protein kinase B activation. |
| 1247 | 11171610 | These results demonstrate that reduced glucose tolerance observed in late adult life after early growth restriction is associated with adipocyte insulin resistance. |
| 1248 | 11238471 | A generally accepted paradigm is that insulin receptors, acting through insulin receptor substrates, stimulate the lipid kinase activity of phosphatidylinositol 3-kinase. |
| 1249 | 11238471 | Among the latter, Akt (a product of the akt protooncogene) and atypical protein kinase C isoforms are thought to be involved in insulin regulation of glucose transport and oxidation; glycogen, lipid, and protein synthesis; and modulation of gene expression. |
| 1250 | 11238471 | Moreover, there exists substantial evidence for insulin receptor substrate- and/or phosphatidylinositol 3-kinase-independent pathways of insulin action. |
| 1251 | 11238471 | A generally accepted paradigm is that insulin receptors, acting through insulin receptor substrates, stimulate the lipid kinase activity of phosphatidylinositol 3-kinase. |
| 1252 | 11238471 | Among the latter, Akt (a product of the akt protooncogene) and atypical protein kinase C isoforms are thought to be involved in insulin regulation of glucose transport and oxidation; glycogen, lipid, and protein synthesis; and modulation of gene expression. |
| 1253 | 11238471 | Moreover, there exists substantial evidence for insulin receptor substrate- and/or phosphatidylinositol 3-kinase-independent pathways of insulin action. |
| 1254 | 11246893 | In vitro and in vivo studies of a naturally occurring variant of the human p85alpha regulatory subunit of the phosphoinositide 3-kinase: inhibition of protein kinase B and relationships with type 2 diabetes, insulin secretion, glucose disappearance constant, and insulin sensitivity. |
| 1255 | 11246893 | In humans, the Met326Ile missense variant of the p85alpha regulatory subunit of the phosphoinositide 3-kinase (PI3K) has been associated with either significant reductions in glucose effectiveness and intravenous glucose tolerance in Caucasians or a significantly higher insulin secretory response in Pima Indians. |
| 1256 | 11246893 | In the present study, we genotyped 1,190 Caucasian males to evaluate the impact in vivo of the Met326Ile variant of the p85alpha subunit of PI3K on the acute insulin response, intravenous glucose tolerance, insulin-mediated glucose uptake, and the prevalence of type 2 diabetes after 20 years of follow-up. |
| 1257 | 11246893 | We also expressed the variant in vitro to evaluate the impact on insulin-stimulated activation of protein kinase B (PKB). |
| 1258 | 11246893 | The Met326Ile variant of p85alpha was not associated with type 2 diabetes or with alterations in insulin secretion, insulin sensitivity, or intravenous glucose tolerance in vivo. |
| 1259 | 11246893 | Expressed in vitro, the Ile326 and the Met326 variant acted equally as a dominant-negative and prevented (60-70% inhibition) insulin-mediated activation of PKB by inhibiting the phosphorylation of PKB at Thr308. |
| 1260 | 11246893 | We conclude that the Met326Ile variant of the p85alpha regulatory subunit of PI3K is likely to be as functionally normal in vivo as in vitro. |
| 1261 | 11246893 | In vitro and in vivo studies of a naturally occurring variant of the human p85alpha regulatory subunit of the phosphoinositide 3-kinase: inhibition of protein kinase B and relationships with type 2 diabetes, insulin secretion, glucose disappearance constant, and insulin sensitivity. |
| 1262 | 11246893 | In humans, the Met326Ile missense variant of the p85alpha regulatory subunit of the phosphoinositide 3-kinase (PI3K) has been associated with either significant reductions in glucose effectiveness and intravenous glucose tolerance in Caucasians or a significantly higher insulin secretory response in Pima Indians. |
| 1263 | 11246893 | In the present study, we genotyped 1,190 Caucasian males to evaluate the impact in vivo of the Met326Ile variant of the p85alpha subunit of PI3K on the acute insulin response, intravenous glucose tolerance, insulin-mediated glucose uptake, and the prevalence of type 2 diabetes after 20 years of follow-up. |
| 1264 | 11246893 | We also expressed the variant in vitro to evaluate the impact on insulin-stimulated activation of protein kinase B (PKB). |
| 1265 | 11246893 | The Met326Ile variant of p85alpha was not associated with type 2 diabetes or with alterations in insulin secretion, insulin sensitivity, or intravenous glucose tolerance in vivo. |
| 1266 | 11246893 | Expressed in vitro, the Ile326 and the Met326 variant acted equally as a dominant-negative and prevented (60-70% inhibition) insulin-mediated activation of PKB by inhibiting the phosphorylation of PKB at Thr308. |
| 1267 | 11246893 | We conclude that the Met326Ile variant of the p85alpha regulatory subunit of PI3K is likely to be as functionally normal in vivo as in vitro. |
| 1268 | 11246893 | In vitro and in vivo studies of a naturally occurring variant of the human p85alpha regulatory subunit of the phosphoinositide 3-kinase: inhibition of protein kinase B and relationships with type 2 diabetes, insulin secretion, glucose disappearance constant, and insulin sensitivity. |
| 1269 | 11246893 | In humans, the Met326Ile missense variant of the p85alpha regulatory subunit of the phosphoinositide 3-kinase (PI3K) has been associated with either significant reductions in glucose effectiveness and intravenous glucose tolerance in Caucasians or a significantly higher insulin secretory response in Pima Indians. |
| 1270 | 11246893 | In the present study, we genotyped 1,190 Caucasian males to evaluate the impact in vivo of the Met326Ile variant of the p85alpha subunit of PI3K on the acute insulin response, intravenous glucose tolerance, insulin-mediated glucose uptake, and the prevalence of type 2 diabetes after 20 years of follow-up. |
| 1271 | 11246893 | We also expressed the variant in vitro to evaluate the impact on insulin-stimulated activation of protein kinase B (PKB). |
| 1272 | 11246893 | The Met326Ile variant of p85alpha was not associated with type 2 diabetes or with alterations in insulin secretion, insulin sensitivity, or intravenous glucose tolerance in vivo. |
| 1273 | 11246893 | Expressed in vitro, the Ile326 and the Met326 variant acted equally as a dominant-negative and prevented (60-70% inhibition) insulin-mediated activation of PKB by inhibiting the phosphorylation of PKB at Thr308. |
| 1274 | 11246893 | We conclude that the Met326Ile variant of the p85alpha regulatory subunit of PI3K is likely to be as functionally normal in vivo as in vitro. |
| 1275 | 11250941 | Rosiglitazone, insulin treatment, and fasting correct defective activation of protein kinase C-zeta/lambda by insulin in vastus lateralis muscles and adipocytes of diabetic rats. |
| 1276 | 11250941 | Atypical protein kinases C (PKCs), zeta and lambda, and protein kinase B (PKB) are thought to function downstream of phosphatidylinositol 3-kinase (PI 3-kinase) and regulate glucose transport during insulin action in skeletal muscle and adipocytes. |
| 1277 | 11250941 | Presently, we evaluated the effects of these insulin-sensitizing modalities on the activation of insulin receptor substrate-1 (IRS-1)-dependent PI 3-kinase, PKC-zeta/lambda, and PKB in vastus lateralis skeletal muscles and adipocytes of nondiabetic and Goto-Kakizaki (GK) diabetic rats. |
| 1278 | 11250941 | Insulin provoked rapid increases in the activity of PI 3-kinase, PKC-zeta/lambda, and PKB in muscles and adipocytes of nondiabetic rats, but increases in IRS-1-dependent PI 3-kinase and PKC-zeta/lambda, but not PKB, activity were substantially diminished in GK muscles and adipocytes. |
| 1279 | 11250941 | Rosiglitazone treatment for 10-14 days, 10-day insulin treatment, and 60-h fasting reversed defects in PKC-zeta/lambda activation in GK muscles and adipocytes and increased glucose transport in GK adipocytes, without necessarily increasing IRS-1-dependent PI 3-kinase or PKB activation. |
| 1280 | 11250941 | Our findings suggest that insulin-sensitizing modalities, viz. thiazolidinediones, chronic insulin treatment, and short-term fasting, similarly improve defects in insulin-stimulated glucose transport at least partly by correcting defects in insulin-induced activation of PKC-zeta/lambda. |
| 1281 | 11272176 | Insulin receptor substrate (IRS) proteins mediate a variety of the metabolic and growth-promoting actions of insulin and IGF-1. |
| 1282 | 11272176 | After phosphorylation by activated receptors, these intracellular signaling molecules recruit various downstream effector pathways including phosphatidylinositol 3-kinase and Grb2. |
| 1283 | 11272176 | Ablation of the IRS-2 gene produces a diabetic phenotype; mice lacking IRS-2 display peripheral insulin resistance and beta-cell dysfunction characterized by a 50% reduction in beta-cell mass. |
| 1284 | 11273003 | Insulin-like growth factor-I and over-expression of Bcl-xL prevent glucose-mediated apoptosis in Schwann cells. |
| 1285 | 11273003 | Insulin-like growth factor-I (IGF-I) is protective. |
| 1286 | 11273003 | LY294002, a phosphatidylinositol 3-kinase (PI 3-kinase) inhibitor, blocks the effect of IGF-I. |
| 1287 | 11273003 | Over-expression of Bcl-xL, or IGF-I, signaling via PI 3-kinase, protects SCs from glucose-mediated apoptosis in vitro. |
| 1288 | 11274905 | Glucose-induced insulin resistance of phosphatidylinositol 3'-OH kinase and AKT/PKB is mediated by the hexosamine biosynthesis pathway. |
| 1289 | 11274905 | Overexpression of GFA in rat-1 fibroblasts results in insulin resistance for glycogen synthase (GS) activity, and renders these cells more sensitive to the effects of glucose. |
| 1290 | 11274905 | Insulin stimulated GS activity was found to occur via a PI-3 kinase (PI-3K)-dependent pathway as wortmannin, an inhibitor of PI-3K, blocked insulin's ability to stimulate GS activity. |
| 1291 | 11274905 | Subsequently, we examined the effects of hexosamines on PI-3K and Akt/PKB activity. |
| 1292 | 11274905 | After treatment with insulin (100 nM) for 5 min, cell extracts were assayed for IRS-1 associated and total PI-3K activity. |
| 1293 | 11274905 | At LG, insulin increased PI-3K activity by 43%. |
| 1294 | 11274905 | There was no insulin stimulation of PI-3K activity in cells cultured in HG or GlcN. |
| 1295 | 11274905 | At LG, insulin stimulated PKB activity. |
| 1296 | 11274905 | Again, both HG and GlcN significantly reduced insulin's ability to stimulate PKB activity. |
| 1297 | 11274905 | We conclude that the hexosamine-mediated insulin resistance of GS activity seen in rat-1 cells is mediated by hexosamine regulation of PI-3K and PKB. |
| 1298 | 11274905 | Glucose-induced insulin resistance of phosphatidylinositol 3'-OH kinase and AKT/PKB is mediated by the hexosamine biosynthesis pathway. |
| 1299 | 11274905 | Overexpression of GFA in rat-1 fibroblasts results in insulin resistance for glycogen synthase (GS) activity, and renders these cells more sensitive to the effects of glucose. |
| 1300 | 11274905 | Insulin stimulated GS activity was found to occur via a PI-3 kinase (PI-3K)-dependent pathway as wortmannin, an inhibitor of PI-3K, blocked insulin's ability to stimulate GS activity. |
| 1301 | 11274905 | Subsequently, we examined the effects of hexosamines on PI-3K and Akt/PKB activity. |
| 1302 | 11274905 | After treatment with insulin (100 nM) for 5 min, cell extracts were assayed for IRS-1 associated and total PI-3K activity. |
| 1303 | 11274905 | At LG, insulin increased PI-3K activity by 43%. |
| 1304 | 11274905 | There was no insulin stimulation of PI-3K activity in cells cultured in HG or GlcN. |
| 1305 | 11274905 | At LG, insulin stimulated PKB activity. |
| 1306 | 11274905 | Again, both HG and GlcN significantly reduced insulin's ability to stimulate PKB activity. |
| 1307 | 11274905 | We conclude that the hexosamine-mediated insulin resistance of GS activity seen in rat-1 cells is mediated by hexosamine regulation of PI-3K and PKB. |
| 1308 | 11274905 | Glucose-induced insulin resistance of phosphatidylinositol 3'-OH kinase and AKT/PKB is mediated by the hexosamine biosynthesis pathway. |
| 1309 | 11274905 | Overexpression of GFA in rat-1 fibroblasts results in insulin resistance for glycogen synthase (GS) activity, and renders these cells more sensitive to the effects of glucose. |
| 1310 | 11274905 | Insulin stimulated GS activity was found to occur via a PI-3 kinase (PI-3K)-dependent pathway as wortmannin, an inhibitor of PI-3K, blocked insulin's ability to stimulate GS activity. |
| 1311 | 11274905 | Subsequently, we examined the effects of hexosamines on PI-3K and Akt/PKB activity. |
| 1312 | 11274905 | After treatment with insulin (100 nM) for 5 min, cell extracts were assayed for IRS-1 associated and total PI-3K activity. |
| 1313 | 11274905 | At LG, insulin increased PI-3K activity by 43%. |
| 1314 | 11274905 | There was no insulin stimulation of PI-3K activity in cells cultured in HG or GlcN. |
| 1315 | 11274905 | At LG, insulin stimulated PKB activity. |
| 1316 | 11274905 | Again, both HG and GlcN significantly reduced insulin's ability to stimulate PKB activity. |
| 1317 | 11274905 | We conclude that the hexosamine-mediated insulin resistance of GS activity seen in rat-1 cells is mediated by hexosamine regulation of PI-3K and PKB. |
| 1318 | 11274905 | Glucose-induced insulin resistance of phosphatidylinositol 3'-OH kinase and AKT/PKB is mediated by the hexosamine biosynthesis pathway. |
| 1319 | 11274905 | Overexpression of GFA in rat-1 fibroblasts results in insulin resistance for glycogen synthase (GS) activity, and renders these cells more sensitive to the effects of glucose. |
| 1320 | 11274905 | Insulin stimulated GS activity was found to occur via a PI-3 kinase (PI-3K)-dependent pathway as wortmannin, an inhibitor of PI-3K, blocked insulin's ability to stimulate GS activity. |
| 1321 | 11274905 | Subsequently, we examined the effects of hexosamines on PI-3K and Akt/PKB activity. |
| 1322 | 11274905 | After treatment with insulin (100 nM) for 5 min, cell extracts were assayed for IRS-1 associated and total PI-3K activity. |
| 1323 | 11274905 | At LG, insulin increased PI-3K activity by 43%. |
| 1324 | 11274905 | There was no insulin stimulation of PI-3K activity in cells cultured in HG or GlcN. |
| 1325 | 11274905 | At LG, insulin stimulated PKB activity. |
| 1326 | 11274905 | Again, both HG and GlcN significantly reduced insulin's ability to stimulate PKB activity. |
| 1327 | 11274905 | We conclude that the hexosamine-mediated insulin resistance of GS activity seen in rat-1 cells is mediated by hexosamine regulation of PI-3K and PKB. |
| 1328 | 11274905 | Glucose-induced insulin resistance of phosphatidylinositol 3'-OH kinase and AKT/PKB is mediated by the hexosamine biosynthesis pathway. |
| 1329 | 11274905 | Overexpression of GFA in rat-1 fibroblasts results in insulin resistance for glycogen synthase (GS) activity, and renders these cells more sensitive to the effects of glucose. |
| 1330 | 11274905 | Insulin stimulated GS activity was found to occur via a PI-3 kinase (PI-3K)-dependent pathway as wortmannin, an inhibitor of PI-3K, blocked insulin's ability to stimulate GS activity. |
| 1331 | 11274905 | Subsequently, we examined the effects of hexosamines on PI-3K and Akt/PKB activity. |
| 1332 | 11274905 | After treatment with insulin (100 nM) for 5 min, cell extracts were assayed for IRS-1 associated and total PI-3K activity. |
| 1333 | 11274905 | At LG, insulin increased PI-3K activity by 43%. |
| 1334 | 11274905 | There was no insulin stimulation of PI-3K activity in cells cultured in HG or GlcN. |
| 1335 | 11274905 | At LG, insulin stimulated PKB activity. |
| 1336 | 11274905 | Again, both HG and GlcN significantly reduced insulin's ability to stimulate PKB activity. |
| 1337 | 11274905 | We conclude that the hexosamine-mediated insulin resistance of GS activity seen in rat-1 cells is mediated by hexosamine regulation of PI-3K and PKB. |
| 1338 | 11274905 | Glucose-induced insulin resistance of phosphatidylinositol 3'-OH kinase and AKT/PKB is mediated by the hexosamine biosynthesis pathway. |
| 1339 | 11274905 | Overexpression of GFA in rat-1 fibroblasts results in insulin resistance for glycogen synthase (GS) activity, and renders these cells more sensitive to the effects of glucose. |
| 1340 | 11274905 | Insulin stimulated GS activity was found to occur via a PI-3 kinase (PI-3K)-dependent pathway as wortmannin, an inhibitor of PI-3K, blocked insulin's ability to stimulate GS activity. |
| 1341 | 11274905 | Subsequently, we examined the effects of hexosamines on PI-3K and Akt/PKB activity. |
| 1342 | 11274905 | After treatment with insulin (100 nM) for 5 min, cell extracts were assayed for IRS-1 associated and total PI-3K activity. |
| 1343 | 11274905 | At LG, insulin increased PI-3K activity by 43%. |
| 1344 | 11274905 | There was no insulin stimulation of PI-3K activity in cells cultured in HG or GlcN. |
| 1345 | 11274905 | At LG, insulin stimulated PKB activity. |
| 1346 | 11274905 | Again, both HG and GlcN significantly reduced insulin's ability to stimulate PKB activity. |
| 1347 | 11274905 | We conclude that the hexosamine-mediated insulin resistance of GS activity seen in rat-1 cells is mediated by hexosamine regulation of PI-3K and PKB. |
| 1348 | 11278970 | Expression of UCP3 in L6 myotubes increased 2-deoxyglucose uptake 2-fold and cell surface GLUT4 2.3-fold, thereby reaching maximally insulin-stimulated levels in control myotubes. |
| 1349 | 11278970 | Wortmannin, LY 294002, or the tyrosine kinase inhibitor genistein abolished the effect of UCP3 on glucose uptake, and wortmannin inhibited UCP3-induced GLUT4 cell surface recruitment. |
| 1350 | 11278970 | UCP3 overexpression increased phosphotyrosine-associated phosphoinositide 3-kinase (PI3K) activity 2.2-fold compared with control cells (p < 0.05). |
| 1351 | 11278970 | In parallel, glucose transport increased 1.3- and 2-fold at 12 h and 7 days, respectively, and the stimulation was inhibited by wortmannin or genistein. p85 association with membranes was increased 5.5-fold and phosphotyrosine-associated PI3K activity 3.8-fold. |
| 1352 | 11278970 | Thus, UCP3 stimulates glucose transport and GLUT4 translocation to the cell surface in cardiac and skeletal muscle cells by activating a PI3K dependent pathway. |
| 1353 | 11278970 | Expression of UCP3 in L6 myotubes increased 2-deoxyglucose uptake 2-fold and cell surface GLUT4 2.3-fold, thereby reaching maximally insulin-stimulated levels in control myotubes. |
| 1354 | 11278970 | Wortmannin, LY 294002, or the tyrosine kinase inhibitor genistein abolished the effect of UCP3 on glucose uptake, and wortmannin inhibited UCP3-induced GLUT4 cell surface recruitment. |
| 1355 | 11278970 | UCP3 overexpression increased phosphotyrosine-associated phosphoinositide 3-kinase (PI3K) activity 2.2-fold compared with control cells (p < 0.05). |
| 1356 | 11278970 | In parallel, glucose transport increased 1.3- and 2-fold at 12 h and 7 days, respectively, and the stimulation was inhibited by wortmannin or genistein. p85 association with membranes was increased 5.5-fold and phosphotyrosine-associated PI3K activity 3.8-fold. |
| 1357 | 11278970 | Thus, UCP3 stimulates glucose transport and GLUT4 translocation to the cell surface in cardiac and skeletal muscle cells by activating a PI3K dependent pathway. |
| 1358 | 11278970 | Expression of UCP3 in L6 myotubes increased 2-deoxyglucose uptake 2-fold and cell surface GLUT4 2.3-fold, thereby reaching maximally insulin-stimulated levels in control myotubes. |
| 1359 | 11278970 | Wortmannin, LY 294002, or the tyrosine kinase inhibitor genistein abolished the effect of UCP3 on glucose uptake, and wortmannin inhibited UCP3-induced GLUT4 cell surface recruitment. |
| 1360 | 11278970 | UCP3 overexpression increased phosphotyrosine-associated phosphoinositide 3-kinase (PI3K) activity 2.2-fold compared with control cells (p < 0.05). |
| 1361 | 11278970 | In parallel, glucose transport increased 1.3- and 2-fold at 12 h and 7 days, respectively, and the stimulation was inhibited by wortmannin or genistein. p85 association with membranes was increased 5.5-fold and phosphotyrosine-associated PI3K activity 3.8-fold. |
| 1362 | 11278970 | Thus, UCP3 stimulates glucose transport and GLUT4 translocation to the cell surface in cardiac and skeletal muscle cells by activating a PI3K dependent pathway. |
| 1363 | 11289048 | TLK16998 alone had no effect on IR signaling in mouse 3T3-L1 adipocytes but, at concentrations as low as 3.2 micromol/l, enhanced the effects of insulin on the phosphorylation of the IR beta-subunit and IR substrate 1, and on the amount of phosphatidylinositol 3-kinase that coimmunoprecipitated with IRS-1. |
| 1364 | 11289049 | The Q allele variant (GLN121) of membrane glycoprotein PC-1 interacts with the insulin receptor and inhibits insulin signaling more effectively than the common K allele variant (LYS121). |
| 1365 | 11289049 | When overexpressed, the membrane glycoprotein PC-1 may play a role in human insulin resistance through the inhibition of insulin receptor (IR) autophosphorylation. |
| 1366 | 11289049 | A PC-1 variant (K121Q, with lysine 121 replaced by glutamine) is also associated with whole-body insulin resistance when not overexpressed. |
| 1367 | 11289049 | In human MCF-7 cells, the Q allele was severalfold more effective (P < 0.05-0.01) than the K allele in reducing insulin stimulation of IR autophosphorylation, insulin receptor substrate-1 phosphorylation, phosphatidylinositol 3-kinase activity, glycogen synthesis, and cell proliferation. |
| 1368 | 11289049 | In transfected MCF-7 cells, 125I-labeled insulin binding and IR content were unchanged, and PC-1 overexpression did not influence IGF-1 stimulation of IGF-1 receptor autophosphorylation. |
| 1369 | 11289049 | This interaction was greater for the Q allele than for the K allele (P < 0.01), suggesting that direct PC-1-IR interactions are important for the PC-1 inhibitory effect on insulin signaling. |
| 1370 | 11334418 | Basal mRNA levels (determined by reverse transcriptase-competitive polymerase chain reaction) of insulin receptor, insulin receptor substrate-1, p85alpha phosphatidylinositol 3-kinase (PI3K), p110alphaPI3K, p110betaPI3K, GLUT4, glycogen synthase, and sterol regulatory-element-binding protein-1c (SREBP-1c) were similar in muscle of control (n = 17), type 2 diabetic (n = 9), type 1 diabetic (n = 9), and nondiabetic obese (n = 9) subjects. |
| 1371 | 11359881 | Effects of insulin-like growth factor-1 on retinal endothelial cell glucose transport and proliferation. |
| 1372 | 11359881 | Insulin-like growth factor-1 (IGF-1) plays important roles in the developing and mature retina and in pathological states characterized by retinal neovascularization, such as diabetic retinopathy. |
| 1373 | 11359881 | IGF-1 stimulated activity of both protein kinase C (PKC) and phosphatidylinositol-3 kinase (PI3 kinase), and both pathways were required for IGF-1-mediated BREC glucose transport and thymidine incorporation. |
| 1374 | 11359881 | Use of a selective inhibitor of the beta isoform of PKC, LY379196, revealed that IGF-1 stimulation of glucose transport was mediated by PKC-beta; however, inhibition of PKC-beta had no effect on BREC proliferation. |
| 1375 | 11375341 | The insulin-stimulated increase in cell-surface GLUT4, assessed using the 2-N-4-(1-azi-2,2,2-trifluoroethyl)benzoyl-1,3-bis-[2-(3)H] (D-mannose-4-yloxy)-2-propylamine exofacial photolabeling technique, was reduced by approximately 70% in the presence of 20 micromol/l indinavir. |
| 1376 | 11375341 | Insulin stimulation of phosphatidylinositol 3-kinase activity and phosphorylation of protein kinase B were not decreased by indinavir. |
| 1377 | 11375341 | These results provide evidence that indinavir inhibits the translocation or intrinsic activity of GLUT4 rather than insulin signaling. |
| 1378 | 11375348 | Subcellular localization of insulin receptor substrate family proteins associated with phosphatidylinositol 3-kinase activity and alterations in lipolysis in primary mouse adipocytes from IRS-1 null mice. |
| 1379 | 11375348 | To clarify the roles of insulin receptor substrate (IRS) family proteins in phosphatidylinositol (PI) 3-kinase activation and insulin actions in adipocytes, we investigated the intracellular localization of IRS family proteins and PI 3-kinase activation in response to insulin by fractionation of mouse adipocytes from wild-type and IRS-1 null mice. |
| 1380 | 11375348 | In adipocytes from wild-type mice, tyrosine-phosphorylated IRS-1 and IRS-2, which were found to associate with PI 3-kinase in response to insulin, were detected in the plasma membrane (PM) and low-density microsome (LDM) fractions. |
| 1381 | 11375348 | In adipocytes from IRS-1-null mice, insulin-stimulated PI 3-kinase activity in anti-phosphotyrosine (alphaPY) immunoprecipitates in the LDM fraction was almost exclusively mediated via IRS-2 and was reduced to 25%; however, insulin-stimulated PI 3-kinase activity in the PM fraction was primarily mediated via IRS-3 and was reduced to 60%. |
| 1382 | 11375348 | To determine the potential functional impact of the distinct subcellular localization of IRSs and associating PI 3-kinase activity on adipocyte-specific metabolic actions, we examined lipolysis in IRS-1 null mice. |
| 1383 | 11375348 | The antilipolytic effect of insulin in IRS-1 null adipocytes, however, was comparable to that in wild-type mice. |
| 1384 | 11375348 | Thus, discordance between these two insulin actions as well as the transcriptional and translational effect (HSL mRNA and protein regulation) and the PM effect (antilipolysis) of insulin may be explained by distinct roles of both PI 3-kinase activity associated with IRS-1/IRS-2 and PI 3-kinase activity associated with IRS-3 in insulin actions related to their subcellular localization. |
| 1385 | 11380072 | The expression of the p85alpha subunit of phosphatidylinositol 3-kinase is induced by activation of the peroxisome proliferator-activated receptor gamma in human adipocytes. |
| 1386 | 11387480 | Insulin resistance and a diabetes mellitus-like syndrome in mice lacking the protein kinase Akt2 (PKB beta). |
| 1387 | 11387480 | The critical initial steps in insulin action include phosphorylation of scaffolding proteins and activation of phosphatidylinositol 3-kinase. |
| 1388 | 11387480 | We show that mice deficient in Akt2 are impaired in the ability of insulin to lower blood glucose because of defects in the action of the hormone on liver and skeletal muscle. |
| 1389 | 11388693 | In a set of in vivo experiments, the levels of alpha subunit of the insulin receptor, the insulin receptor substrate 1 (IRS-1) and the phosphatidylinositol 3-kinase (PI3K) were determined. [3H]-thymidine incorporation into DNA 24 or 48 h after surgery was assessed in all the experimental groups. |
| 1390 | 11388693 | IRS-1 and PI3K showed similar increases. |
| 1391 | 11388693 | In conclusion, increased expression of IR and IRS-1 leads to increased association of PI3K in vivo in diabetic regenerating rats. |
| 1392 | 11388693 | In a set of in vivo experiments, the levels of alpha subunit of the insulin receptor, the insulin receptor substrate 1 (IRS-1) and the phosphatidylinositol 3-kinase (PI3K) were determined. [3H]-thymidine incorporation into DNA 24 or 48 h after surgery was assessed in all the experimental groups. |
| 1393 | 11388693 | IRS-1 and PI3K showed similar increases. |
| 1394 | 11388693 | In conclusion, increased expression of IR and IRS-1 leads to increased association of PI3K in vivo in diabetic regenerating rats. |
| 1395 | 11388693 | In a set of in vivo experiments, the levels of alpha subunit of the insulin receptor, the insulin receptor substrate 1 (IRS-1) and the phosphatidylinositol 3-kinase (PI3K) were determined. [3H]-thymidine incorporation into DNA 24 or 48 h after surgery was assessed in all the experimental groups. |
| 1396 | 11388693 | IRS-1 and PI3K showed similar increases. |
| 1397 | 11388693 | In conclusion, increased expression of IR and IRS-1 leads to increased association of PI3K in vivo in diabetic regenerating rats. |
| 1398 | 11390966 | Tissue-specific overexpression of lipoprotein lipase causes tissue-specific insulin resistance. |
| 1399 | 11390966 | Transgenic mice with muscle- and liver-specific overexpression of lipoprotein lipase were studied during a 2-h hyperinsulinemic-euglycemic clamp to determine the effect of tissue-specific increase in fat on insulin action and signaling. |
| 1400 | 11390966 | Muscle-lipoprotein lipase mice had a 3-fold increase in muscle triglyceride content and were insulin resistant because of decreases in insulin-stimulated glucose uptake in skeletal muscle and insulin activation of insulin receptor substrate-1-associated phosphatidylinositol 3-kinase activity. |
| 1401 | 11390966 | In contrast, liver-lipoprotein lipase mice had a 2-fold increase in liver triglyceride content and were insulin resistant because of impaired ability of insulin to suppress endogenous glucose production associated with defects in insulin activation of insulin receptor substrate-2-associated phosphatidylinositol 3-kinase activity. |
| 1402 | 11390966 | Tissue-specific overexpression of lipoprotein lipase causes tissue-specific insulin resistance. |
| 1403 | 11390966 | Transgenic mice with muscle- and liver-specific overexpression of lipoprotein lipase were studied during a 2-h hyperinsulinemic-euglycemic clamp to determine the effect of tissue-specific increase in fat on insulin action and signaling. |
| 1404 | 11390966 | Muscle-lipoprotein lipase mice had a 3-fold increase in muscle triglyceride content and were insulin resistant because of decreases in insulin-stimulated glucose uptake in skeletal muscle and insulin activation of insulin receptor substrate-1-associated phosphatidylinositol 3-kinase activity. |
| 1405 | 11390966 | In contrast, liver-lipoprotein lipase mice had a 2-fold increase in liver triglyceride content and were insulin resistant because of impaired ability of insulin to suppress endogenous glucose production associated with defects in insulin activation of insulin receptor substrate-2-associated phosphatidylinositol 3-kinase activity. |
| 1406 | 11402048 | Insulin-stimulated activation of eNOS is independent of Ca2+ but requires phosphorylation by Akt at Ser(1179). |
| 1407 | 11402048 | Vasodilator actions of insulin are mediated by activation of endothelial nitric-oxide synthase (eNOS) and subsequent production of NO. |
| 1408 | 11402048 | Phosphatidylinositol 3-kinase and Akt play important roles in insulin-signaling pathways leading to production of NO in vascular endothelium. |
| 1409 | 11402048 | Here we dissected mechanisms whereby insulin activates eNOS by using the fluorescent dye DAF-2 to directly measure NO production in single cells. |
| 1410 | 11402048 | Insulin caused a rapid increase in intracellular NO in NIH-3T3(IR) cells transiently transfected with eNOS. |
| 1411 | 11402048 | However, cells expressing the eNOS-S1179A mutant (disrupted Akt phosphorylation site) did not produce detectable NO in response to insulin, whereas the response to LPA was similar to that observed in cells expressing wild-type eNOS. |
| 1412 | 11402048 | Moreover, production of NO in response to insulin was blocked by coexpression of an inhibitory mutant of Akt, whereas the response to LPA was unaffected. |
| 1413 | 11402048 | Phosphorylation of eNOS at Ser(1179) was observed only in response to treatment with insulin, but not with LPA. |
| 1414 | 11402048 | Interestingly, platelet-derived growth factor treatment of cells activated Akt but not eNOS. |
| 1415 | 11402048 | We conclude that insulin regulates eNOS activity using a Ca(2+)-independent mechanism requiring phosphorylation of eNOS by Akt. |
| 1416 | 11412137 | Glucose transport, the rate limiting step in glucose metabolism, is mediated by glucose transporter 4 (GLUT4) and can be activated in skeletal muscle by two separate and distinct signalling pathways; one stimulated by insulin and the second by muscle contractions. |
| 1417 | 11412137 | Defects in insulin signal transduction through the insulin-receptor substrate-1/phosphatidylinositol 3-kinase pathway are associated with reduced insulin-stimulated glucose transporter 4 translocation and glucose transport activity in skeletal muscle from type II diabetic patients. |
| 1418 | 11433005 | In non-diabetic cells, the stimulatory effect of insulin on adenosine transport was mimicked by dibutyryl cGMP (100 nM) and reduced by inhibitors of phosphatidylinositol 3-kinase (10 nM wortmannin), nitric oxide synthase (100 microM N (G)-nitro-L-arginine methyl ester, L-NAME) or protein synthesis (1 microM cycloheximide), whereas inhibition of adenylyl cyclase (100 microM SQ-22536) had no effect. 5. |
| 1419 | 11433005 | Protein levels of inducible NO synthase (iNOS) were similar in non-diabetic and diabetic cells, but were increased by insulin (1 nM, 8 h) only in non-diabetic smooth muscle cells. 7. |
| 1420 | 11433005 | Our results suggest that adenosine transport via the es nucleoside transporter is modulated differentially by insulin in either cell type. |
| 1421 | 11433005 | Insulin increased adenosine transport in non-diabetic cells via NO and cGMP, but inhibited the diabetes-elevated adenosine transport via activation of adenylyl cyclase, suggesting that the biological actions of adenosine may be altered under conditions of sustained hyperglycaemia in uncontrolled diabetes. |
| 1422 | 11440917 | Insulin receptor substrate (IRS)-1-associated phosphatidylinositol 3-kinase (PI 3K) activity was significantly decreased in PCOS (n = 12) compared with control skeletal muscle (n = 8; P < 0.05). |
| 1423 | 11440917 | There was no significant difference in the abundance of IR, IRS-1, or the p85 regulatory subunit of PI 3K in PCOS (n = 14) compared with control (n = 12) muscle. |
| 1424 | 11459778 | After IGF-I stimulation, insulin receptor substrate-1 and -2 phosphorylation and PI3K activity were restored to levels similar to or greater than those seen in wild-type cells. |
| 1425 | 11463381 | Selective insulin signaling through A and B insulin receptors regulates transcription of insulin and glucokinase genes in pancreatic beta cells. |
| 1426 | 11463381 | We show here that insulin activates the transcription of its own gene and that of the beta cell glucokinase gene (betaGK) by different mechanisms. |
| 1427 | 11463381 | Whereas insulin gene transcription is promoted by signaling through insulin receptor A type (Ex11-), PI3K class Ia, and p70s6k, insulin stimulates the betaGK gene by signaling via insulin receptor B type (Ex11+), PI3K class II-like activity, and PKB (c-Akt). |
| 1428 | 11463381 | Our data provide evidence for selectivity in insulin action via the two isoforms of the insulin receptor, the molecular basis being preferential signaling through different PI3K and protein kinases. |
| 1429 | 11463381 | Selective insulin signaling through A and B insulin receptors regulates transcription of insulin and glucokinase genes in pancreatic beta cells. |
| 1430 | 11463381 | We show here that insulin activates the transcription of its own gene and that of the beta cell glucokinase gene (betaGK) by different mechanisms. |
| 1431 | 11463381 | Whereas insulin gene transcription is promoted by signaling through insulin receptor A type (Ex11-), PI3K class Ia, and p70s6k, insulin stimulates the betaGK gene by signaling via insulin receptor B type (Ex11+), PI3K class II-like activity, and PKB (c-Akt). |
| 1432 | 11463381 | Our data provide evidence for selectivity in insulin action via the two isoforms of the insulin receptor, the molecular basis being preferential signaling through different PI3K and protein kinases. |
| 1433 | 11463795 | Glucose activates protein kinase C-zeta /lambda through proline-rich tyrosine kinase-2, extracellular signal-regulated kinase, and phospholipase D: a novel mechanism for activating glucose transporter translocation. |
| 1434 | 11463795 | Insulin controls glucose uptake by translocating GLUT4 and other glucose transporters to the plasma membrane in muscle and adipose tissues by a mechanism that appears to require protein kinase C (PKC)-zeta/lambda operating downstream of phosphatidylinositol 3-kinase. |
| 1435 | 11463795 | Presently, we found that glucose acutely activated PKC-zeta/lambda in rat adipocytes and rat skeletal muscle preparations by a mechanism that was independent of phosphatidylinositol 3-kinase but, interestingly, dependent on the apparently sequential activation of the dantrolene-sensitive, nonreceptor proline-rich tyrosine kinase-2; components of the extracellular signal-regulated kinase (ERK) pathway, including, GRB2, SOS, RAS, RAF, MEK1 and ERK1/2; and, most interestingly, phospholipase D, thus yielding increases in phosphatidic acid, a known activator of PKC-zeta/lambda. |
| 1436 | 11463795 | This activation of PKC-zeta/lambda, moreover, appeared to be required for glucose-induced increases in GLUT4 translocation and glucose transport in adipocytes and muscle cells. |
| 1437 | 11463795 | Glucose activates protein kinase C-zeta /lambda through proline-rich tyrosine kinase-2, extracellular signal-regulated kinase, and phospholipase D: a novel mechanism for activating glucose transporter translocation. |
| 1438 | 11463795 | Insulin controls glucose uptake by translocating GLUT4 and other glucose transporters to the plasma membrane in muscle and adipose tissues by a mechanism that appears to require protein kinase C (PKC)-zeta/lambda operating downstream of phosphatidylinositol 3-kinase. |
| 1439 | 11463795 | Presently, we found that glucose acutely activated PKC-zeta/lambda in rat adipocytes and rat skeletal muscle preparations by a mechanism that was independent of phosphatidylinositol 3-kinase but, interestingly, dependent on the apparently sequential activation of the dantrolene-sensitive, nonreceptor proline-rich tyrosine kinase-2; components of the extracellular signal-regulated kinase (ERK) pathway, including, GRB2, SOS, RAS, RAF, MEK1 and ERK1/2; and, most interestingly, phospholipase D, thus yielding increases in phosphatidic acid, a known activator of PKC-zeta/lambda. |
| 1440 | 11463795 | This activation of PKC-zeta/lambda, moreover, appeared to be required for glucose-induced increases in GLUT4 translocation and glucose transport in adipocytes and muscle cells. |
| 1441 | 11472733 | Glucosamine enhances platelet-derived growth factor-induced DNA synthesis via phosphatidylinositol 3-kinase pathway in rat aortic smooth muscle cells. |
| 1442 | 11472733 | Culture of vascular smooth muscle A10 cells with high glucose for 4 weeks enhanced platelet-derived growth factor (PDGF)-induced BrdU incorporation. |
| 1443 | 11472733 | Of the subsequent intracellular signaling pathways, PDGF-induced PDGF beta-receptor association with PLC gamma was not affected, whereas tyrosine phosphorylation of Shc, subsequent association of Shc with Grb2, and MAP kinase activation were relatively decreased. |
| 1444 | 11472733 | In contrast, PDGF-induced PDGF beta-receptor association with the p85 regulatory subunit of PI3-kinase and PI3-kinase activation were increased by 20% (P<0.01) and 36% (P<0.01), respectively. |
| 1445 | 11472733 | Pretreatment with PLC inhibitor (U73122) had negligible effects, and MEK1 inhibitor (PD98059) showed only a slight inhibitory effect on the PDGF-induced BrdU incorporation. |
| 1446 | 11472733 | In contrast, pretreatment with PI3-kinase inhibitor (LY294002) significantly inhibited glucosamine enhancement of PDGF-induced BrdU incorporation. |
| 1447 | 11472733 | These findings suggest that glucosamine is involved in the development of atherosclerosis by enhancing PDGF-induced mitogenesis specifically via the PI3-kinase pathway. |
| 1448 | 11473053 | Growth hormone induces cellular insulin resistance by uncoupling phosphatidylinositol 3-kinase and its downstream signals in 3T3-L1 adipocytes. |
| 1449 | 11473053 | In this study, we demonstrated that chronic GH treatment of differentiated 3T3-L1 adipocytes reduces insulin-stimulated 2-deoxyglucose (DOG) uptake and activation of Akt (also known as protein kinase B), both of which are downstream effects of phosphatidylinositol (PI) 3-kinase, despite enhanced tyrosine phosphorylation of insulin receptor substrate (IRS)-1, association of IRS-1 with the p85 subunit of PI 3-kinase, and IRS-1-associated PI 3-kinase activity. |
| 1450 | 11473053 | In contrast, chronic GH treatment did not affect 2-DOG uptake and Akt activation induced by overexpression of a membrane-targeted form of the p110 subunit of PI 3-kinase (p110(CAAX)) or Akt activation stimulated by platelet-derived growth factor. |
| 1451 | 11473053 | Fractionation studies indicated that chronic GH treatment reduces insulin-stimulated translocation of Akt from the cytosol to the plasma membrane. |
| 1452 | 11473053 | Interestingly, chronic GH treatment increased insulin-stimulated association of IRS-1 with p85 and IRS-1-associated PI 3-kinase activity preferentially in the cytosol. |
| 1453 | 11518806 | Glucose-dependent insulinotropic polypeptide is a growth factor for beta (INS-1) cells by pleiotropic signaling. |
| 1454 | 11518806 | Activation of the G-protein-coupled receptor for glucose-dependent insulinotropic polypeptide facilitates insulin-release from pancreatic beta-cells. |
| 1455 | 11518806 | In the present study, we examined whether glucose-dependent insulinotropic polypeptide also acts as a growth factor for the beta-cell line INS-1. |
| 1456 | 11518806 | Glucose-dependent insulinotropic polypeptide stimulated the signaling modules of PKA/cAMP regulatory element binder, MAPK, and PI3K/protein kinase B in a glucose- and dose-dependent manner. |
| 1457 | 11518806 | Janus kinase 2 and signal transducer and activators of transcription 5/6 pathways were not stimulated by glucose-dependent insulinotropic polypeptide. |
| 1458 | 11518806 | Activation of PI3K by glucose-dependent insulinotropic polypeptide and glucose was associated with insulin receptor substrate isoforms insulin receptor substrate-2 and growth factor bound-2 associated binder-1 and PI3K isoforms p85alpha, p110alpha, p110beta, and p110gamma. |
| 1459 | 11518806 | Downstream of PI3K, glucose-dependent insulinotropic polypeptide-stimulated protein kinase Balpha and protein kinase Bbeta isoforms and phosphorylated glycogen synthase kinase-3, forkhead transcription factor FKHR, and p70S6K. |
| 1460 | 11518806 | These data indicate that glucose-dependent insulinotropic polypeptide functions synergistically with glucose as a pleiotropic growth factor for insulin-producing beta-cells, which may play a role for metabolic adaptations of insulin-producing cells during type II diabetes. |
| 1461 | 11518806 | Glucose-dependent insulinotropic polypeptide is a growth factor for beta (INS-1) cells by pleiotropic signaling. |
| 1462 | 11518806 | Activation of the G-protein-coupled receptor for glucose-dependent insulinotropic polypeptide facilitates insulin-release from pancreatic beta-cells. |
| 1463 | 11518806 | In the present study, we examined whether glucose-dependent insulinotropic polypeptide also acts as a growth factor for the beta-cell line INS-1. |
| 1464 | 11518806 | Glucose-dependent insulinotropic polypeptide stimulated the signaling modules of PKA/cAMP regulatory element binder, MAPK, and PI3K/protein kinase B in a glucose- and dose-dependent manner. |
| 1465 | 11518806 | Janus kinase 2 and signal transducer and activators of transcription 5/6 pathways were not stimulated by glucose-dependent insulinotropic polypeptide. |
| 1466 | 11518806 | Activation of PI3K by glucose-dependent insulinotropic polypeptide and glucose was associated with insulin receptor substrate isoforms insulin receptor substrate-2 and growth factor bound-2 associated binder-1 and PI3K isoforms p85alpha, p110alpha, p110beta, and p110gamma. |
| 1467 | 11518806 | Downstream of PI3K, glucose-dependent insulinotropic polypeptide-stimulated protein kinase Balpha and protein kinase Bbeta isoforms and phosphorylated glycogen synthase kinase-3, forkhead transcription factor FKHR, and p70S6K. |
| 1468 | 11518806 | These data indicate that glucose-dependent insulinotropic polypeptide functions synergistically with glucose as a pleiotropic growth factor for insulin-producing beta-cells, which may play a role for metabolic adaptations of insulin-producing cells during type II diabetes. |
| 1469 | 11518806 | Glucose-dependent insulinotropic polypeptide is a growth factor for beta (INS-1) cells by pleiotropic signaling. |
| 1470 | 11518806 | Activation of the G-protein-coupled receptor for glucose-dependent insulinotropic polypeptide facilitates insulin-release from pancreatic beta-cells. |
| 1471 | 11518806 | In the present study, we examined whether glucose-dependent insulinotropic polypeptide also acts as a growth factor for the beta-cell line INS-1. |
| 1472 | 11518806 | Glucose-dependent insulinotropic polypeptide stimulated the signaling modules of PKA/cAMP regulatory element binder, MAPK, and PI3K/protein kinase B in a glucose- and dose-dependent manner. |
| 1473 | 11518806 | Janus kinase 2 and signal transducer and activators of transcription 5/6 pathways were not stimulated by glucose-dependent insulinotropic polypeptide. |
| 1474 | 11518806 | Activation of PI3K by glucose-dependent insulinotropic polypeptide and glucose was associated with insulin receptor substrate isoforms insulin receptor substrate-2 and growth factor bound-2 associated binder-1 and PI3K isoforms p85alpha, p110alpha, p110beta, and p110gamma. |
| 1475 | 11518806 | Downstream of PI3K, glucose-dependent insulinotropic polypeptide-stimulated protein kinase Balpha and protein kinase Bbeta isoforms and phosphorylated glycogen synthase kinase-3, forkhead transcription factor FKHR, and p70S6K. |
| 1476 | 11518806 | These data indicate that glucose-dependent insulinotropic polypeptide functions synergistically with glucose as a pleiotropic growth factor for insulin-producing beta-cells, which may play a role for metabolic adaptations of insulin-producing cells during type II diabetes. |
| 1477 | 11546773 | Regulation of insulin/insulin-like growth factor-1 signaling by proteasome-mediated degradation of insulin receptor substrate-2. |
| 1478 | 11546773 | Insulin and insulin-like growth factor-1 (IGF-1) regulate metabolism and body growth through homologous receptor tyrosine kinases that phosphorylate the insulin receptor substrate (IRS) proteins. |
| 1479 | 11546773 | IRS-2 is an important IRS protein, as it mediates peripheral insulin action and beta-cell survival. |
| 1480 | 11546773 | In this study, we show that insulin, IGF-1, or osmotic stress promoted ubiquitin/proteasome-mediated degradation of IRS-2 in 3T3-L1 cells, Fao hepatoma, cells and mouse embryo fibroblasts; however, insulin/IGF-1 did not promote degradation of IRS-1 in 3T3-L1 preadipocytes or mouse embryo fibroblasts. |
| 1481 | 11546773 | MG132 or lactacystin, specific inhibitors of 26S proteasome, blocked insulin/IGF-1-induced degradation of IRS-2 and enhanced the detection of ubiquitinated IRS-2. |
| 1482 | 11546773 | Insulin/IGF1-induced ubiquitination and degradation of IRS-2 was blocked by inhibitors of phosphatidylinositol 3-kinase (wortmannin or LY294002) or mTOR (rapamycin). |
| 1483 | 11546773 | Chronic insulin or IGF-1 treatment of IRS-1-deficient mouse embryo fibroblasts inhibited IRS-2-mediated activation of Akt and ERK1/2, which was reversed by lactacystin pretreatment. |
| 1484 | 11546773 | By contrast, IRS-1 activation of Akt and ERK1/2 was not inhibited by chronic insulin/IGF-1 stimulation in IRS-2-deficient mouse embryo fibroblasts. |
| 1485 | 11546773 | Thus, we identified a novel negative feedback mechanism by which the ubiquitin/proteasome-mediated degradation of IRS-2 limits the magnitude and duration of the response to insulin or IGF-1. |
| 1486 | 11549666 | Insulin stimulation of glycogen synthase activity as well as phosphorylation of MAPK, p70 S6 kinase, and protein kinase B (Akt) were blocked by the phosphatidylinositol 3-kinase inhibitors wortmannin (50 nM) and LY294002 (10 microM). |
| 1487 | 11549666 | This increased sensitivity of diabetic muscle to impairment of insulin-stimulated glycogen synthase activity occurs together with diminished insulin-stimulation (by 40%) of IRS-1-associated phosphatidylinositol 3-kinase activity in the same cells. |
| 1488 | 11549666 | Protein expression of IRS-1, p85, p110, Akt, p70 S6 kinase, and MAPK were normal in diabetic cells, as was insulin-stimulated phosphorylation of Akt, p70 S6 kinase, and MAPK. |
| 1489 | 11549666 | These studies indicate that, despite prolonged growth and differentiation of diabetic muscle under normal metabolic culture conditions, defects of insulin-stimulated phosphatidylinositol 3-kinase and glycogen synthase activity in diabetic muscle persist, consistent with intrinsic (rather than acquired) defects of insulin action. |
| 1490 | 11549666 | Insulin stimulation of glycogen synthase activity as well as phosphorylation of MAPK, p70 S6 kinase, and protein kinase B (Akt) were blocked by the phosphatidylinositol 3-kinase inhibitors wortmannin (50 nM) and LY294002 (10 microM). |
| 1491 | 11549666 | This increased sensitivity of diabetic muscle to impairment of insulin-stimulated glycogen synthase activity occurs together with diminished insulin-stimulation (by 40%) of IRS-1-associated phosphatidylinositol 3-kinase activity in the same cells. |
| 1492 | 11549666 | Protein expression of IRS-1, p85, p110, Akt, p70 S6 kinase, and MAPK were normal in diabetic cells, as was insulin-stimulated phosphorylation of Akt, p70 S6 kinase, and MAPK. |
| 1493 | 11549666 | These studies indicate that, despite prolonged growth and differentiation of diabetic muscle under normal metabolic culture conditions, defects of insulin-stimulated phosphatidylinositol 3-kinase and glycogen synthase activity in diabetic muscle persist, consistent with intrinsic (rather than acquired) defects of insulin action. |
| 1494 | 11549666 | Insulin stimulation of glycogen synthase activity as well as phosphorylation of MAPK, p70 S6 kinase, and protein kinase B (Akt) were blocked by the phosphatidylinositol 3-kinase inhibitors wortmannin (50 nM) and LY294002 (10 microM). |
| 1495 | 11549666 | This increased sensitivity of diabetic muscle to impairment of insulin-stimulated glycogen synthase activity occurs together with diminished insulin-stimulation (by 40%) of IRS-1-associated phosphatidylinositol 3-kinase activity in the same cells. |
| 1496 | 11549666 | Protein expression of IRS-1, p85, p110, Akt, p70 S6 kinase, and MAPK were normal in diabetic cells, as was insulin-stimulated phosphorylation of Akt, p70 S6 kinase, and MAPK. |
| 1497 | 11549666 | These studies indicate that, despite prolonged growth and differentiation of diabetic muscle under normal metabolic culture conditions, defects of insulin-stimulated phosphatidylinositol 3-kinase and glycogen synthase activity in diabetic muscle persist, consistent with intrinsic (rather than acquired) defects of insulin action. |
| 1498 | 11563968 | Intact actin microfilaments are required for insulin-regulated glucose transporter isoform 4 (GLUT4) translocation to the plasma membrane. |
| 1499 | 11563968 | In the present investigation, ventricular cardiomyocytes were used to study the effects of two structurally different LO inhibitors (esculetin and nordihydroguaiaretic acid) on insulin signalling events, glucose uptake, GLUT4 translocation and the actin network organization. |
| 1500 | 11563968 | This was paralleled by a slight reduction in the insulin-induced tyrosine phosphorylation of insulin receptor substrate (IRS)-1 and IRS-2. |
| 1501 | 11563968 | However, inhibition of 12-LO did not affect the association of phosphatidylinositol 3-kinase with IRS-1 and the phosphorylation of Akt/protein kinase B in response to insulin. |
| 1502 | 11563968 | Insulin stimulation increased cell surface GLUT4 2-fold in control cells, whereas LO inhibition abrogated the insulin-stimulated GLUT4 translocation. |
| 1503 | 11563968 | LO inhibition blocks GLUT4 translocation without affecting downstream insulin signalling. |
| 1504 | 11571295 | In this report, we show that injection of insulin and glycated albumin (Alb-AGE) to mice increases VEGF mRNA expression in eyes. |
| 1505 | 11571295 | Insulin and Alb-AGE stimulate VEGF mRNA and protein expression in retinal epithelial cells (ARPE-19). |
| 1506 | 11571295 | Alb-AGE-induced VEGF expression is not modulated by the use of antioxidants, N-acetyl-l-cysteine or pyrrolidinedithiocarbamate, or by an inhibitor of phosphatidylinositol 3-kinase (PI3K), wortmannin. |
| 1507 | 11571295 | However, using an inhibitor of ERK activation, U0126, we show that Alb-AGE stimulates VEGF expression through an ERK-dependent pathway. |
| 1508 | 11571295 | Accordingly, we found that Alb-AGE activated mitogen-activate protein kinase, ERK1/2, JNK1/2, but not p38, and that Alb-AGE did not activate PI3K and PKB. |
| 1509 | 11571295 | Moreover, Alb-AGE activated the transcription factor, hypoxia inducible factor-1 (HIF-1) DNA binding activity. |
| 1510 | 11571295 | This activation is mediated by an increase in accumulation of the HIF-1alpha protein through an ERK-dependent pathway. |
| 1511 | 11571295 | Thus, stimulation of VEGF expression by Alb-AGE, through the activation of HIF-1, could play an important role in the development of diabetic retinopathy. |
| 1512 | 11571295 | In this report, we show that injection of insulin and glycated albumin (Alb-AGE) to mice increases VEGF mRNA expression in eyes. |
| 1513 | 11571295 | Insulin and Alb-AGE stimulate VEGF mRNA and protein expression in retinal epithelial cells (ARPE-19). |
| 1514 | 11571295 | Alb-AGE-induced VEGF expression is not modulated by the use of antioxidants, N-acetyl-l-cysteine or pyrrolidinedithiocarbamate, or by an inhibitor of phosphatidylinositol 3-kinase (PI3K), wortmannin. |
| 1515 | 11571295 | However, using an inhibitor of ERK activation, U0126, we show that Alb-AGE stimulates VEGF expression through an ERK-dependent pathway. |
| 1516 | 11571295 | Accordingly, we found that Alb-AGE activated mitogen-activate protein kinase, ERK1/2, JNK1/2, but not p38, and that Alb-AGE did not activate PI3K and PKB. |
| 1517 | 11571295 | Moreover, Alb-AGE activated the transcription factor, hypoxia inducible factor-1 (HIF-1) DNA binding activity. |
| 1518 | 11571295 | This activation is mediated by an increase in accumulation of the HIF-1alpha protein through an ERK-dependent pathway. |
| 1519 | 11571295 | Thus, stimulation of VEGF expression by Alb-AGE, through the activation of HIF-1, could play an important role in the development of diabetic retinopathy. |
| 1520 | 11574397 | Insulin activates ATP-sensitive K(+) channels in pancreatic beta-cells through a phosphatidylinositol 3-kinase-dependent pathway. |
| 1521 | 11574404 | We previously provided evidence that GLP-1 induces pancreatic beta-cell growth nonadditively with glucose in a phosphatidylinositol-3 kinase (PI-3K)-dependent manner. |
| 1522 | 11574404 | In the present study, we investigated the downstream effectors of PI-3K to determine the precise signal transduction pathways that mediate the action of GLP-1 on beta-cell proliferation. |
| 1523 | 11574404 | GLP-1 increased extracellular signal-related kinase 1/2, p38 mitogen-activated protein kinase (MAPK), and protein kinase B activities nonadditively with glucose in pancreatic beta(INS 832/13) cells. |
| 1524 | 11574404 | GLP-1 also caused nuclear translocation of the atypical protein kinase C (aPKC) zeta isoform in INS as well as in dissociated normal rat beta-cells as shown by immunolocalization and Western immunoblotting analysis. |
| 1525 | 11574404 | Tritiated thymidine incorporation measurements showed that the p38 MAPK inhibitor SB203580 suppressed GLP-1-induced beta-cell proliferation. |
| 1526 | 11574404 | The PKCzeta pseudosubstrate suppressed the proliferative action of GLP-1, whereas the inhibitor of classical PKC isoforms had no effect. |
| 1527 | 11574404 | In addition, ectopic expression of a constitutively active PKCzeta mutant stimulated tritiated thymidine incorporation to the same extent as GLP-1, and the glucoincretin had no growth-promoting action under this condition. |
| 1528 | 11574404 | The results are consistent with a model in which GLP-1-induced PI-3K activation results in PKCzeta translocation to the nucleus, which may play a role in the pleiotropic effects (DNA synthesis, metabolic enzymes, and insulin gene expression) of the glucoincretin. |
| 1529 | 11574404 | We previously provided evidence that GLP-1 induces pancreatic beta-cell growth nonadditively with glucose in a phosphatidylinositol-3 kinase (PI-3K)-dependent manner. |
| 1530 | 11574404 | In the present study, we investigated the downstream effectors of PI-3K to determine the precise signal transduction pathways that mediate the action of GLP-1 on beta-cell proliferation. |
| 1531 | 11574404 | GLP-1 increased extracellular signal-related kinase 1/2, p38 mitogen-activated protein kinase (MAPK), and protein kinase B activities nonadditively with glucose in pancreatic beta(INS 832/13) cells. |
| 1532 | 11574404 | GLP-1 also caused nuclear translocation of the atypical protein kinase C (aPKC) zeta isoform in INS as well as in dissociated normal rat beta-cells as shown by immunolocalization and Western immunoblotting analysis. |
| 1533 | 11574404 | Tritiated thymidine incorporation measurements showed that the p38 MAPK inhibitor SB203580 suppressed GLP-1-induced beta-cell proliferation. |
| 1534 | 11574404 | The PKCzeta pseudosubstrate suppressed the proliferative action of GLP-1, whereas the inhibitor of classical PKC isoforms had no effect. |
| 1535 | 11574404 | In addition, ectopic expression of a constitutively active PKCzeta mutant stimulated tritiated thymidine incorporation to the same extent as GLP-1, and the glucoincretin had no growth-promoting action under this condition. |
| 1536 | 11574404 | The results are consistent with a model in which GLP-1-induced PI-3K activation results in PKCzeta translocation to the nucleus, which may play a role in the pleiotropic effects (DNA synthesis, metabolic enzymes, and insulin gene expression) of the glucoincretin. |
| 1537 | 11574404 | We previously provided evidence that GLP-1 induces pancreatic beta-cell growth nonadditively with glucose in a phosphatidylinositol-3 kinase (PI-3K)-dependent manner. |
| 1538 | 11574404 | In the present study, we investigated the downstream effectors of PI-3K to determine the precise signal transduction pathways that mediate the action of GLP-1 on beta-cell proliferation. |
| 1539 | 11574404 | GLP-1 increased extracellular signal-related kinase 1/2, p38 mitogen-activated protein kinase (MAPK), and protein kinase B activities nonadditively with glucose in pancreatic beta(INS 832/13) cells. |
| 1540 | 11574404 | GLP-1 also caused nuclear translocation of the atypical protein kinase C (aPKC) zeta isoform in INS as well as in dissociated normal rat beta-cells as shown by immunolocalization and Western immunoblotting analysis. |
| 1541 | 11574404 | Tritiated thymidine incorporation measurements showed that the p38 MAPK inhibitor SB203580 suppressed GLP-1-induced beta-cell proliferation. |
| 1542 | 11574404 | The PKCzeta pseudosubstrate suppressed the proliferative action of GLP-1, whereas the inhibitor of classical PKC isoforms had no effect. |
| 1543 | 11574404 | In addition, ectopic expression of a constitutively active PKCzeta mutant stimulated tritiated thymidine incorporation to the same extent as GLP-1, and the glucoincretin had no growth-promoting action under this condition. |
| 1544 | 11574404 | The results are consistent with a model in which GLP-1-induced PI-3K activation results in PKCzeta translocation to the nucleus, which may play a role in the pleiotropic effects (DNA synthesis, metabolic enzymes, and insulin gene expression) of the glucoincretin. |
| 1545 | 11574405 | Pancreatic duodenal homeobox-1 (PDX-1) is a homeodomain protein that plays an important role in the development of the pancreas and in maintaining the identity and function of the islets of Langerhans. |
| 1546 | 11574405 | Glucose and insulin regulate PDX-1 by way of a signaling pathway involving phosphatidylinositol 3-kinase (PI 3-kinase) and SAPK2/p38. |
| 1547 | 11574405 | Insulin and sodium arsenite, an activator of the stress-activated pathway, also stimulated PDX-1 movement from the nuclear periphery to the nucleoplasm. |
| 1548 | 11574405 | Glucose- and insulin-stimulated translocation of PDX-1 to the nucleoplasm was inhibited by wortmannin and SB 203580, indicating that a pathway involving PI 3-kinase and SAPK2/p38 was involved; translocation was unaffected by PD 098959 and rapamycin, suggesting that neither mitogen-activated protein kinase nor p70(s6k) were involved. |
| 1549 | 11574405 | These results demonstrated that PDX-1 shuttles between the nuclear periphery and nucleoplasm in response to changes in glucose and insulin concentrations and that these events are dependent on PI 3-kinase, SAPK2/p38, and a nuclear phosphatase(s). |
| 1550 | 11598104 | 5'-AMP-activated protein kinase phosphorylates IRS-1 on Ser-789 in mouse C2C12 myotubes in response to 5-aminoimidazole-4-carboxamide riboside. |
| 1551 | 11598104 | Activation of 5'-AMP-activated protein kinase (AMPK) by 5-aminoimidazole-4-carboxamide riboside (AICAR), exercise, or electrically stimulated contraction leads to increased glucose transport in skeletal muscle. |
| 1552 | 11598104 | Here we report the first evidence of a direct interaction between AMPK and the most upstream component of the insulin-signaling cascade, insulin receptor substrate-1 (IRS-1). |
| 1553 | 11598104 | We find that AMPK rapidly phosphorylates IRS-1 on Ser-789 in cell-free assays as well as in mouse C2C12 myotubes incubated with AICAR. |
| 1554 | 11598104 | In the C2C12 myotubes activation of AMPK by AICAR matched the phosphorylation of IRS-1 on Ser-789. |
| 1555 | 11598104 | This phosphorylation correlates with a 65% increase in insulin-stimulated IRS-1-associated phosphatidylinositol 3-kinase activity in C2C12 myotubes preincubated with AICAR. |
| 1556 | 11598104 | The binding of phosphatidylinositol 3-kinase to IRS-1 was not affected by AICAR. |
| 1557 | 11598104 | These results demonstrate the existence of an interaction between AMPK and early insulin signaling that could be of importance to our understanding of the potentiating effects of exercise on insulin signaling. |
| 1558 | 11598104 | 5'-AMP-activated protein kinase phosphorylates IRS-1 on Ser-789 in mouse C2C12 myotubes in response to 5-aminoimidazole-4-carboxamide riboside. |
| 1559 | 11598104 | Activation of 5'-AMP-activated protein kinase (AMPK) by 5-aminoimidazole-4-carboxamide riboside (AICAR), exercise, or electrically stimulated contraction leads to increased glucose transport in skeletal muscle. |
| 1560 | 11598104 | Here we report the first evidence of a direct interaction between AMPK and the most upstream component of the insulin-signaling cascade, insulin receptor substrate-1 (IRS-1). |
| 1561 | 11598104 | We find that AMPK rapidly phosphorylates IRS-1 on Ser-789 in cell-free assays as well as in mouse C2C12 myotubes incubated with AICAR. |
| 1562 | 11598104 | In the C2C12 myotubes activation of AMPK by AICAR matched the phosphorylation of IRS-1 on Ser-789. |
| 1563 | 11598104 | This phosphorylation correlates with a 65% increase in insulin-stimulated IRS-1-associated phosphatidylinositol 3-kinase activity in C2C12 myotubes preincubated with AICAR. |
| 1564 | 11598104 | The binding of phosphatidylinositol 3-kinase to IRS-1 was not affected by AICAR. |
| 1565 | 11598104 | These results demonstrate the existence of an interaction between AMPK and early insulin signaling that could be of importance to our understanding of the potentiating effects of exercise on insulin signaling. |
| 1566 | 11606564 | One serine residue located near the phosphotyrosine-binding (PTB) domain in IRS-1 (Ser(307) in rat IRS-1 or Ser(312) in human IRS-1) is phosphorylated via several mechanisms, including insulin-stimulated kinases or stress-activated kinases like JNK1. |
| 1567 | 11606564 | During a yeast tri-hybrid assay, phosphorylation of Ser(307) by JNK1 disrupted the interaction between the catalytic domain of the insulin receptor and the PTB domain of IRS-1. |
| 1568 | 11606564 | In 32D myeloid progenitor cells, phosphorylation of Ser(307) inhibited insulin stimulation of the phosphatidylinositol 3-kinase and MAPK cascades. |
| 1569 | 11606564 | These results suggest that inhibition of PTB domain function in IRS-1 by phosphorylation of Ser(307) (Ser(312) in human IRS-1) might be a general mechanism to regulate insulin signaling. |
| 1570 | 11672473 | To clarify diabetic complications mediated by increased platelet activity, we have studied platelet aggregation and its second messenger molecules such as protein kinase C (PKC), RhoA, and phosphatidylinositol 3-kinase (PI3- kinase), in six diabetic patients with diabetic retinopathy and other diabetic complications in spite of good glycemic control. |
| 1571 | 11672473 | PKC, RhoA and PI3-kinase activities in the cytosol- and membrane-associated fractions were examined in the platelets from the two patients (Cases 2 and 4). |
| 1572 | 11672473 | Platelet membrane-associated RhoA and PI3-kinase activity in Case 2 were increased before the stimulation. |
| 1573 | 11672473 | Membrane-associated immunoreactive PKC alpha, but not PKC beta in Cases 2 and 4 was elevated. |
| 1574 | 11672473 | These results suggest that hyperreactivity of PKC alpha may lead to increased RhoA and PI3-kinase activities and platelet hyperfunction in diabetic patients with good glycemic control, and that raised platelet PKC alpha may be implicated in the pathogenesis of diabetic complications. |
| 1575 | 11679440 | Rosiglitazone (BRL 49653) enhances insulin secretory response via phosphatidylinositol 3-kinase pathway. |
| 1576 | 11679440 | To elucidate the direct effect of rosiglitazone (RSG), a new thiazolidinedione antihyperglycemic agent, on pancreatic insulin secretion, an in situ investigation by rat pancreatic perfusion was performed. |
| 1577 | 11679440 | The effects of RSG on insulin secretion were inhibited by a phosphatidylinositol 3-kinase (PI3K) inhibitor, LY294002. |
| 1578 | 11679440 | These results suggest that RSG has a direct potentiation effect on insulin secretion in the presence of 10 mmol/l glucose, mediated through PI3K activity. |
| 1579 | 11679440 | Rosiglitazone (BRL 49653) enhances insulin secretory response via phosphatidylinositol 3-kinase pathway. |
| 1580 | 11679440 | To elucidate the direct effect of rosiglitazone (RSG), a new thiazolidinedione antihyperglycemic agent, on pancreatic insulin secretion, an in situ investigation by rat pancreatic perfusion was performed. |
| 1581 | 11679440 | The effects of RSG on insulin secretion were inhibited by a phosphatidylinositol 3-kinase (PI3K) inhibitor, LY294002. |
| 1582 | 11679440 | These results suggest that RSG has a direct potentiation effect on insulin secretion in the presence of 10 mmol/l glucose, mediated through PI3K activity. |
| 1583 | 11679440 | Rosiglitazone (BRL 49653) enhances insulin secretory response via phosphatidylinositol 3-kinase pathway. |
| 1584 | 11679440 | To elucidate the direct effect of rosiglitazone (RSG), a new thiazolidinedione antihyperglycemic agent, on pancreatic insulin secretion, an in situ investigation by rat pancreatic perfusion was performed. |
| 1585 | 11679440 | The effects of RSG on insulin secretion were inhibited by a phosphatidylinositol 3-kinase (PI3K) inhibitor, LY294002. |
| 1586 | 11679440 | These results suggest that RSG has a direct potentiation effect on insulin secretion in the presence of 10 mmol/l glucose, mediated through PI3K activity. |
| 1587 | 11694503 | Stretch-induced retinal vascular endothelial growth factor expression is mediated by phosphatidylinositol 3-kinase and protein kinase C (PKC)-zeta but not by stretch-induced ERK1/2, Akt, Ras, or classical/novel PKC pathways. |
| 1588 | 11694503 | We present novel findings demonstrating that stretch-induced VEGF expression in retinal capillary pericytes is mediated by phosphatidylinositol (PI) 3-kinase and protein kinase C (PKC)-zeta but is not mediated by ERK1/2, classical/novel isoforms of PKC, Akt, or Ras despite their activation by stretch. |
| 1589 | 11694503 | Stretch increased ERK1/2 phosphorylation, PI 3-kinase activity, Akt phosphorylation, and PKC-zeta activity. |
| 1590 | 11694503 | Signaling pathways were explored using inhibitors of PKC, MEK1/2, and PI 3-kinase; adenovirus-mediated overexpression of ERK, PKC-alpha, PKC-delta, PKC-zeta, and Akt; and dominant negative (DN) mutants of ERK, PKC-zeta, Ras, PI 3-kinase and Akt. |
| 1591 | 11694503 | Although stretch activated ERK1/2 through a Ras- and PKC classical/novel isoform-dependent pathway, these pathways were not responsible for stretch-induced VEGF expression. |
| 1592 | 11694503 | Overexpression of DN ERK and Ras had no effect on VEGF expression in these cells. |
| 1593 | 11694503 | Although stretch-induced PI 3-kinase activation increased both Akt phosphorylation and activity of PKC-zeta, VEGF expression was dependent on PKC-zeta but not Akt. |
| 1594 | 11694503 | In addition, PKC-zeta did not mediate stretch-induced ERK1/2 activation. |
| 1595 | 11694503 | These results suggest that stretch-induced expression of VEGF involves a novel mechanism dependent upon PI 3-kinase-mediated activation of PKC-zeta that is independent of stretch-induced activation of ERK1/2, classical/novel PKC isoforms, Ras, or Akt. |
| 1596 | 11701440 | Normal Akt/PKB with reduced PI3K activation in insulin-resistant mice. |
| 1597 | 11701440 | Similarly, adipocytes from insulin-resistant mice have diminished insulin-stimulated IRS-1 phosphorylation and phosphatidylinositol 3-kinase (PI3K) activation. |
| 1598 | 11701440 | However, normal activation of protein kinase B (Akt/PKB) by insulin is observed. |
| 1599 | 11701440 | Thus BtB6 mice demonstrate the dissociation of insulin-stimulated PI3K activity and Akt/PKB activation and represent a useful model to investigate the causes of insulin resistance in humans. |
| 1600 | 11701440 | Normal Akt/PKB with reduced PI3K activation in insulin-resistant mice. |
| 1601 | 11701440 | Similarly, adipocytes from insulin-resistant mice have diminished insulin-stimulated IRS-1 phosphorylation and phosphatidylinositol 3-kinase (PI3K) activation. |
| 1602 | 11701440 | However, normal activation of protein kinase B (Akt/PKB) by insulin is observed. |
| 1603 | 11701440 | Thus BtB6 mice demonstrate the dissociation of insulin-stimulated PI3K activity and Akt/PKB activation and represent a useful model to investigate the causes of insulin resistance in humans. |
| 1604 | 11701440 | Normal Akt/PKB with reduced PI3K activation in insulin-resistant mice. |
| 1605 | 11701440 | Similarly, adipocytes from insulin-resistant mice have diminished insulin-stimulated IRS-1 phosphorylation and phosphatidylinositol 3-kinase (PI3K) activation. |
| 1606 | 11701440 | However, normal activation of protein kinase B (Akt/PKB) by insulin is observed. |
| 1607 | 11701440 | Thus BtB6 mice demonstrate the dissociation of insulin-stimulated PI3K activity and Akt/PKB activation and represent a useful model to investigate the causes of insulin resistance in humans. |
| 1608 | 11701445 | Activation of Elk-1, an Ets transcription factor, by glucose and EGF treatment of insulinoma cells. |
| 1609 | 11701445 | Treatment with either epidermal growth factor (EGF), a known inducer of beta-cell hyperplasia, glucose, or KCl-induced depolarization resulted in Ser(383) phosphorylation and transcriptional activation of Elk-1 (4 +/- 0.3-, P = 0.003, 2.3 +/- 0.19-, P = 0.002, and 2.2 +/- 0.1- fold, P = 0.001 respectively). |
| 1610 | 11701445 | EGF-induced activation of Elk-1 was also inhibited by PD98059 (60 +/- 5%). |
| 1611 | 11701445 | Experiments with p38, phosphatidylinositol 3-kinase, and protein kinase A inhibitors indicated that these pathways are not involved. |
| 1612 | 11701445 | Furthermore, the results demonstrated a convergence of nutrient- and growth factor-mediated signaling pathways on Elk-1 activation through induction of Ras/mitogen-activated protein kinase ERK-1 and -2. |
| 1613 | 11707433 | Inhibition of phosphatidylinositol 3-kinase enhances mitogenic actions of insulin in endothelial cells. |
| 1614 | 11707433 | To explore this hypothesis in endothelial cells, we designed a set of experiments to mimic the "typical metabolic insulin resistance" by blocking the phosphatidylinositol 3-kinase pathway and exposing the cells to increasing concentrations of insulin ("compensatory hyperinsulinemia"). |
| 1615 | 11707433 | Inhibition of phosphatidylinositol 3-kinase with wortmannin blocked the ability of insulin to stimulate increased expression of endothelial nitric-oxide synthase, did not affect insulin-induced activation of MAP kinase, and increased the effects of insulin on prenylation of Ras and Rho proteins. |
| 1616 | 11707433 | Inhibition of phosphatidylinositol 3-kinase enhances mitogenic actions of insulin in endothelial cells. |
| 1617 | 11707433 | To explore this hypothesis in endothelial cells, we designed a set of experiments to mimic the "typical metabolic insulin resistance" by blocking the phosphatidylinositol 3-kinase pathway and exposing the cells to increasing concentrations of insulin ("compensatory hyperinsulinemia"). |
| 1618 | 11707433 | Inhibition of phosphatidylinositol 3-kinase with wortmannin blocked the ability of insulin to stimulate increased expression of endothelial nitric-oxide synthase, did not affect insulin-induced activation of MAP kinase, and increased the effects of insulin on prenylation of Ras and Rho proteins. |
| 1619 | 11707433 | Inhibition of phosphatidylinositol 3-kinase enhances mitogenic actions of insulin in endothelial cells. |
| 1620 | 11707433 | To explore this hypothesis in endothelial cells, we designed a set of experiments to mimic the "typical metabolic insulin resistance" by blocking the phosphatidylinositol 3-kinase pathway and exposing the cells to increasing concentrations of insulin ("compensatory hyperinsulinemia"). |
| 1621 | 11707433 | Inhibition of phosphatidylinositol 3-kinase with wortmannin blocked the ability of insulin to stimulate increased expression of endothelial nitric-oxide synthase, did not affect insulin-induced activation of MAP kinase, and increased the effects of insulin on prenylation of Ras and Rho proteins. |
| 1622 | 11711055 | Hypertension often complicates type 2 diabetes mellitus, and angiotensin converting enzyme inhibitor treatment has been shown to improve insulin resistance in such cases. |
| 1623 | 11711055 | However, the effect of angiotensin II type-1 (AT(1)) receptor antagonists on insulin resistance is still controversial. |
| 1624 | 11711055 | Although Akt activity and glucose transporter type 4 (GLUT4) expressions were not affected by losartan with or without exercise, extracellular signal-regulated kinase (ERK1/2) and p38 mitogen-activated protein (MAP) kinase activities were increased by both interventions. |
| 1625 | 11711055 | These results indicate that angiotensin AT(1) receptor antagonist improved local insulin resistance, but not systemic insulin resistance. |
| 1626 | 11711055 | These findings may explain the controversy over the effect of angiotensin AT(1) receptor antagonists on insulin resistance in clinical use. |
| 1627 | 11711055 | The enhancing effect of angiotensin AT(1) receptor antagonist on skeletal muscle glucose uptake may be attributable to MAP kinase activation or other mechanisms rather than phosphatidylinositol 3-kinase activation. |
| 1628 | 11723053 | The levels of insulin-stimulated tyrosine phosphorylation of the insulin receptor beta-subunit, insulin receptor substrate (IRS)-2, and p52(Shc) were increased in diabetic compared with control heart, whereas tyrosine phosphorylation of IRS-1 was unchanged. |
| 1629 | 11723053 | The amount of the p85 subunit of phosphatidylinositol 3-kinase (PI 3-kinase) and the level of PI 3-kinase activity associated with IRS-2 were also elevated in diabetes, whereas no changes in IRS-1-associated PI 3-kinase were observed. |
| 1630 | 11723053 | Insulin-induced phosphorylation of Akt on Thr-308 was increased fivefold in diabetic heart, whereas Akt phosphorylation on Ser-473 was normal. |
| 1631 | 11723053 | In contrast with Akt phosphorylation, insulin-induced phosphorylation of glycogen synthase kinase (GSK)-3, a major cellular substrate of Akt, was markedly reduced in diabetes. |
| 1632 | 11723053 | In islet-transplanted rats, the majority of the alterations in insulin-signaling proteins found in diabetic rats were normalized, but insulin stimulation of IRS-2 tyrosine phosphorylation and association with PI 3-kinase was blunted. |
| 1633 | 11723053 | In conclusion, in the diabetic heart, 1) IRS-1, IRS-2, and p52(Shc) are differently altered, 2) the levels of Akt phosphorylation on Ser-473 and Thr-308, respectively, are not coordinately regulated, and 3) the increased activity of proximal-signaling proteins (i.e., IRS-2 and PI 3-kinase) is not propagated distally to GSK-3. |
| 1634 | 11739394 | Active Rho kinase (ROK-alpha ) associates with insulin receptor substrate-1 and inhibits insulin signaling in vascular smooth muscle cells. |
| 1635 | 11739394 | Recent studies from our laboratory have shown that insulin stimulates myosin-bound phosphatase (MBP) in vascular smooth muscle cells (VSMCs) by decreasing site-specific phosphorylation of the myosin-bound subunit (MBS) of MBP via nitric oxide/cGMP-mediated Rho/Rho kinase inactivation. |
| 1636 | 11739394 | Here we tested potential interactions between Rho kinase and insulin signaling pathways. |
| 1637 | 11739394 | In control VSMCs, insulin inactivates ROK-alpha, the major Rho kinase isoform in VSMCs, and inhibits thrombin-induced increase in ROK-alpha association with the insulin receptor substrate-1 (IRS-1). |
| 1638 | 11739394 | Hypertension (in spontaneous hypertensive rats) or expression of an active RhoA(V14) up-regulates Rho kinase activity and increases ROK-alpha/IRS-1 association resulting in IRS-1 serine phosphorylation that leads to inhibition of both insulin-induced IRS-1 tyrosine phosphorylation and phosphatidylinositol 3-kinase (PI3-kinase) activation. |
| 1639 | 11739394 | In contrast, expression of dominant negative RhoA or cGMP-dependent protein kinase type I alpha inactivates Rho kinase, abolishes ROK-alpha/IRS-1 association, and potentiates insulin-induced tyrosine phosphorylation and PI3-kinase activation leading to decreased MBS(T695) phosphorylation and decreased MBP inhibition. |
| 1640 | 11739394 | Collectively, these results suggest a novel function for ROK-alpha in insulin signal transduction at the level of IRS-1 and potential cross-talk between cGMP-dependent protein kinase type I alpha, Rho/Rho kinase signaling, and insulin signaling at the level of IRS-1/PI3-kinase. |
| 1641 | 11751589 | Ceramide and glucosamine antagonism of alternate signaling pathways regulating insulin- and osmotic shock-induced glucose transporter 4 translocation. |
| 1642 | 11751589 | In addition to insulin, hyperosmolarity induces glucose transporter 4 (GLUT4) translocation in 3T3-L1 adipocytes. |
| 1643 | 11751589 | However, in contrast to insulin this stimulation is independent of PI3K/Akt. |
| 1644 | 11751589 | In this study we assessed whether ceramide and/or glucosamine, two known insulin-signaling antagonists, also affected the PI3K/Akt-independent signal. |
| 1645 | 11751589 | Insulin, but not hyperosmolarity, clearly increased the activities of PI3K and Akt. |
| 1646 | 11751589 | C2-ceramide did not alter insulin-stimulated PI3K activity, but did decrease the ability of insulin to activate Akt and GLUT4 translocation. |
| 1647 | 11751589 | Consistent with osmotic shock-mediated GLUT4 translocation being independent of PI3K/Akt, GLUT4 translocation induced by hyperosmolarity was not altered by C2-ceramide. |
| 1648 | 11751589 | In contrast to the specific C2-ceramide-induced attenuation of insulin-stimulated GLUT4 translocation, overexpression of glutamine:fructose-6-phosphate amidotransferase, the rate-limiting enzyme in the synthesis of UDP-N-acetylglucosamine, and/or pretreatment of cells with glucosamine, a precursor of UDP-N-acetylglucosamine, inhibited both insulin- and hyperosmolarity-stimulated GLUT4 translocation. |
| 1649 | 11751589 | These data suggest that although the hyperosmolarity-induced signal bypasses the initial insulin signal transduction steps, it is likely to induce GLUT4 translocation through activation of a common convergent signal transduction step, targeted by UDP-N-acetylglucosamine, downstream of and/or in parallel to PI3K/Akt. |
| 1650 | 11751589 | Ceramide and glucosamine antagonism of alternate signaling pathways regulating insulin- and osmotic shock-induced glucose transporter 4 translocation. |
| 1651 | 11751589 | In addition to insulin, hyperosmolarity induces glucose transporter 4 (GLUT4) translocation in 3T3-L1 adipocytes. |
| 1652 | 11751589 | However, in contrast to insulin this stimulation is independent of PI3K/Akt. |
| 1653 | 11751589 | In this study we assessed whether ceramide and/or glucosamine, two known insulin-signaling antagonists, also affected the PI3K/Akt-independent signal. |
| 1654 | 11751589 | Insulin, but not hyperosmolarity, clearly increased the activities of PI3K and Akt. |
| 1655 | 11751589 | C2-ceramide did not alter insulin-stimulated PI3K activity, but did decrease the ability of insulin to activate Akt and GLUT4 translocation. |
| 1656 | 11751589 | Consistent with osmotic shock-mediated GLUT4 translocation being independent of PI3K/Akt, GLUT4 translocation induced by hyperosmolarity was not altered by C2-ceramide. |
| 1657 | 11751589 | In contrast to the specific C2-ceramide-induced attenuation of insulin-stimulated GLUT4 translocation, overexpression of glutamine:fructose-6-phosphate amidotransferase, the rate-limiting enzyme in the synthesis of UDP-N-acetylglucosamine, and/or pretreatment of cells with glucosamine, a precursor of UDP-N-acetylglucosamine, inhibited both insulin- and hyperosmolarity-stimulated GLUT4 translocation. |
| 1658 | 11751589 | These data suggest that although the hyperosmolarity-induced signal bypasses the initial insulin signal transduction steps, it is likely to induce GLUT4 translocation through activation of a common convergent signal transduction step, targeted by UDP-N-acetylglucosamine, downstream of and/or in parallel to PI3K/Akt. |
| 1659 | 11751589 | Ceramide and glucosamine antagonism of alternate signaling pathways regulating insulin- and osmotic shock-induced glucose transporter 4 translocation. |
| 1660 | 11751589 | In addition to insulin, hyperosmolarity induces glucose transporter 4 (GLUT4) translocation in 3T3-L1 adipocytes. |
| 1661 | 11751589 | However, in contrast to insulin this stimulation is independent of PI3K/Akt. |
| 1662 | 11751589 | In this study we assessed whether ceramide and/or glucosamine, two known insulin-signaling antagonists, also affected the PI3K/Akt-independent signal. |
| 1663 | 11751589 | Insulin, but not hyperosmolarity, clearly increased the activities of PI3K and Akt. |
| 1664 | 11751589 | C2-ceramide did not alter insulin-stimulated PI3K activity, but did decrease the ability of insulin to activate Akt and GLUT4 translocation. |
| 1665 | 11751589 | Consistent with osmotic shock-mediated GLUT4 translocation being independent of PI3K/Akt, GLUT4 translocation induced by hyperosmolarity was not altered by C2-ceramide. |
| 1666 | 11751589 | In contrast to the specific C2-ceramide-induced attenuation of insulin-stimulated GLUT4 translocation, overexpression of glutamine:fructose-6-phosphate amidotransferase, the rate-limiting enzyme in the synthesis of UDP-N-acetylglucosamine, and/or pretreatment of cells with glucosamine, a precursor of UDP-N-acetylglucosamine, inhibited both insulin- and hyperosmolarity-stimulated GLUT4 translocation. |
| 1667 | 11751589 | These data suggest that although the hyperosmolarity-induced signal bypasses the initial insulin signal transduction steps, it is likely to induce GLUT4 translocation through activation of a common convergent signal transduction step, targeted by UDP-N-acetylglucosamine, downstream of and/or in parallel to PI3K/Akt. |
| 1668 | 11751589 | Ceramide and glucosamine antagonism of alternate signaling pathways regulating insulin- and osmotic shock-induced glucose transporter 4 translocation. |
| 1669 | 11751589 | In addition to insulin, hyperosmolarity induces glucose transporter 4 (GLUT4) translocation in 3T3-L1 adipocytes. |
| 1670 | 11751589 | However, in contrast to insulin this stimulation is independent of PI3K/Akt. |
| 1671 | 11751589 | In this study we assessed whether ceramide and/or glucosamine, two known insulin-signaling antagonists, also affected the PI3K/Akt-independent signal. |
| 1672 | 11751589 | Insulin, but not hyperosmolarity, clearly increased the activities of PI3K and Akt. |
| 1673 | 11751589 | C2-ceramide did not alter insulin-stimulated PI3K activity, but did decrease the ability of insulin to activate Akt and GLUT4 translocation. |
| 1674 | 11751589 | Consistent with osmotic shock-mediated GLUT4 translocation being independent of PI3K/Akt, GLUT4 translocation induced by hyperosmolarity was not altered by C2-ceramide. |
| 1675 | 11751589 | In contrast to the specific C2-ceramide-induced attenuation of insulin-stimulated GLUT4 translocation, overexpression of glutamine:fructose-6-phosphate amidotransferase, the rate-limiting enzyme in the synthesis of UDP-N-acetylglucosamine, and/or pretreatment of cells with glucosamine, a precursor of UDP-N-acetylglucosamine, inhibited both insulin- and hyperosmolarity-stimulated GLUT4 translocation. |
| 1676 | 11751589 | These data suggest that although the hyperosmolarity-induced signal bypasses the initial insulin signal transduction steps, it is likely to induce GLUT4 translocation through activation of a common convergent signal transduction step, targeted by UDP-N-acetylglucosamine, downstream of and/or in parallel to PI3K/Akt. |
| 1677 | 11751589 | Ceramide and glucosamine antagonism of alternate signaling pathways regulating insulin- and osmotic shock-induced glucose transporter 4 translocation. |
| 1678 | 11751589 | In addition to insulin, hyperosmolarity induces glucose transporter 4 (GLUT4) translocation in 3T3-L1 adipocytes. |
| 1679 | 11751589 | However, in contrast to insulin this stimulation is independent of PI3K/Akt. |
| 1680 | 11751589 | In this study we assessed whether ceramide and/or glucosamine, two known insulin-signaling antagonists, also affected the PI3K/Akt-independent signal. |
| 1681 | 11751589 | Insulin, but not hyperosmolarity, clearly increased the activities of PI3K and Akt. |
| 1682 | 11751589 | C2-ceramide did not alter insulin-stimulated PI3K activity, but did decrease the ability of insulin to activate Akt and GLUT4 translocation. |
| 1683 | 11751589 | Consistent with osmotic shock-mediated GLUT4 translocation being independent of PI3K/Akt, GLUT4 translocation induced by hyperosmolarity was not altered by C2-ceramide. |
| 1684 | 11751589 | In contrast to the specific C2-ceramide-induced attenuation of insulin-stimulated GLUT4 translocation, overexpression of glutamine:fructose-6-phosphate amidotransferase, the rate-limiting enzyme in the synthesis of UDP-N-acetylglucosamine, and/or pretreatment of cells with glucosamine, a precursor of UDP-N-acetylglucosamine, inhibited both insulin- and hyperosmolarity-stimulated GLUT4 translocation. |
| 1685 | 11751589 | These data suggest that although the hyperosmolarity-induced signal bypasses the initial insulin signal transduction steps, it is likely to induce GLUT4 translocation through activation of a common convergent signal transduction step, targeted by UDP-N-acetylglucosamine, downstream of and/or in parallel to PI3K/Akt. |
| 1686 | 11751589 | Ceramide and glucosamine antagonism of alternate signaling pathways regulating insulin- and osmotic shock-induced glucose transporter 4 translocation. |
| 1687 | 11751589 | In addition to insulin, hyperosmolarity induces glucose transporter 4 (GLUT4) translocation in 3T3-L1 adipocytes. |
| 1688 | 11751589 | However, in contrast to insulin this stimulation is independent of PI3K/Akt. |
| 1689 | 11751589 | In this study we assessed whether ceramide and/or glucosamine, two known insulin-signaling antagonists, also affected the PI3K/Akt-independent signal. |
| 1690 | 11751589 | Insulin, but not hyperosmolarity, clearly increased the activities of PI3K and Akt. |
| 1691 | 11751589 | C2-ceramide did not alter insulin-stimulated PI3K activity, but did decrease the ability of insulin to activate Akt and GLUT4 translocation. |
| 1692 | 11751589 | Consistent with osmotic shock-mediated GLUT4 translocation being independent of PI3K/Akt, GLUT4 translocation induced by hyperosmolarity was not altered by C2-ceramide. |
| 1693 | 11751589 | In contrast to the specific C2-ceramide-induced attenuation of insulin-stimulated GLUT4 translocation, overexpression of glutamine:fructose-6-phosphate amidotransferase, the rate-limiting enzyme in the synthesis of UDP-N-acetylglucosamine, and/or pretreatment of cells with glucosamine, a precursor of UDP-N-acetylglucosamine, inhibited both insulin- and hyperosmolarity-stimulated GLUT4 translocation. |
| 1694 | 11751589 | These data suggest that although the hyperosmolarity-induced signal bypasses the initial insulin signal transduction steps, it is likely to induce GLUT4 translocation through activation of a common convergent signal transduction step, targeted by UDP-N-acetylglucosamine, downstream of and/or in parallel to PI3K/Akt. |
| 1695 | 11752399 | Increased insulin sensitivity in mice lacking p85beta subunit of phosphoinositide 3-kinase. |
| 1696 | 11752399 | On the basis of ex vivo studies using insulin-responsive cells, activation of a Class IA phosphoinositide 3-kinase (PI3K) seems to be required for a wide variety of cellular responses downstream of insulin. |
| 1697 | 11752399 | In mammals, insulin-responsive tissues express both the p85alpha and p85beta isoforms of the regulatory subunit. |
| 1698 | 11752399 | Surprisingly, recent studies have revealed that disruption of the p85alpha gene in the mouse (p85alpha(-/-) mice) results in hypoglycemia with decreased plasma insulin, and the p85alpha(+/-) mice exhibit significantly increased insulin sensitivity. |
| 1699 | 11752399 | These results suggest either that p85alpha negatively regulates insulin signaling, or that p85beta, which mediates the major fraction of Class IA PI3K signaling in the absence of p85alpha, is more efficient than p85alpha in mediating insulin responses. |
| 1700 | 11752399 | As with the p85alpha(-/-) mice, the p85beta(-/-) mice showed hypoinsulinemia, hypoglycemia, and improved insulin sensitivity. |
| 1701 | 11752399 | Moreover, insulin-induced activation of AKT was significantly up-regulated in muscle from the p85beta(-/-) mice. |
| 1702 | 11752399 | In addition, insulin-dependent tyrosine phosphorylation of insulin receptor substrate-2 was enhanced in the p85beta(-/-) mice, a phenotype not observed in the p85alpha(-/-) mice. |
| 1703 | 11752399 | These results indicate that in addition to their roles in recruiting the catalytic subunit of PI3K to the insulin receptor substrate proteins, both p85alpha and p85beta play negative roles in insulin signaling. |
| 1704 | 11752399 | Increased insulin sensitivity in mice lacking p85beta subunit of phosphoinositide 3-kinase. |
| 1705 | 11752399 | On the basis of ex vivo studies using insulin-responsive cells, activation of a Class IA phosphoinositide 3-kinase (PI3K) seems to be required for a wide variety of cellular responses downstream of insulin. |
| 1706 | 11752399 | In mammals, insulin-responsive tissues express both the p85alpha and p85beta isoforms of the regulatory subunit. |
| 1707 | 11752399 | Surprisingly, recent studies have revealed that disruption of the p85alpha gene in the mouse (p85alpha(-/-) mice) results in hypoglycemia with decreased plasma insulin, and the p85alpha(+/-) mice exhibit significantly increased insulin sensitivity. |
| 1708 | 11752399 | These results suggest either that p85alpha negatively regulates insulin signaling, or that p85beta, which mediates the major fraction of Class IA PI3K signaling in the absence of p85alpha, is more efficient than p85alpha in mediating insulin responses. |
| 1709 | 11752399 | As with the p85alpha(-/-) mice, the p85beta(-/-) mice showed hypoinsulinemia, hypoglycemia, and improved insulin sensitivity. |
| 1710 | 11752399 | Moreover, insulin-induced activation of AKT was significantly up-regulated in muscle from the p85beta(-/-) mice. |
| 1711 | 11752399 | In addition, insulin-dependent tyrosine phosphorylation of insulin receptor substrate-2 was enhanced in the p85beta(-/-) mice, a phenotype not observed in the p85alpha(-/-) mice. |
| 1712 | 11752399 | These results indicate that in addition to their roles in recruiting the catalytic subunit of PI3K to the insulin receptor substrate proteins, both p85alpha and p85beta play negative roles in insulin signaling. |
| 1713 | 11752399 | Increased insulin sensitivity in mice lacking p85beta subunit of phosphoinositide 3-kinase. |
| 1714 | 11752399 | On the basis of ex vivo studies using insulin-responsive cells, activation of a Class IA phosphoinositide 3-kinase (PI3K) seems to be required for a wide variety of cellular responses downstream of insulin. |
| 1715 | 11752399 | In mammals, insulin-responsive tissues express both the p85alpha and p85beta isoforms of the regulatory subunit. |
| 1716 | 11752399 | Surprisingly, recent studies have revealed that disruption of the p85alpha gene in the mouse (p85alpha(-/-) mice) results in hypoglycemia with decreased plasma insulin, and the p85alpha(+/-) mice exhibit significantly increased insulin sensitivity. |
| 1717 | 11752399 | These results suggest either that p85alpha negatively regulates insulin signaling, or that p85beta, which mediates the major fraction of Class IA PI3K signaling in the absence of p85alpha, is more efficient than p85alpha in mediating insulin responses. |
| 1718 | 11752399 | As with the p85alpha(-/-) mice, the p85beta(-/-) mice showed hypoinsulinemia, hypoglycemia, and improved insulin sensitivity. |
| 1719 | 11752399 | Moreover, insulin-induced activation of AKT was significantly up-regulated in muscle from the p85beta(-/-) mice. |
| 1720 | 11752399 | In addition, insulin-dependent tyrosine phosphorylation of insulin receptor substrate-2 was enhanced in the p85beta(-/-) mice, a phenotype not observed in the p85alpha(-/-) mice. |
| 1721 | 11752399 | These results indicate that in addition to their roles in recruiting the catalytic subunit of PI3K to the insulin receptor substrate proteins, both p85alpha and p85beta play negative roles in insulin signaling. |
| 1722 | 11756318 | Phosphatidylinositol 3-kinase redistribution is associated with skeletal muscle insulin resistance in gestational diabetes mellitus. |
| 1723 | 11756318 | In conjunction with the redistribution of PI 3-kinase to the insulin receptor, there is a selective increase in activation of downstream serine kinases Akt and p70S6. |
| 1724 | 11756318 | Furthermore, we show that redistribution of PI 3-kinase to the insulin receptor increases insulin-stimulated IRS-1 serine phosphorylation, impairs IRS-1 expression and its tyrosine phosphorylation, and decreases the ability of IRS-1 to bind and activate PI 3-kinase in response to insulin. |
| 1725 | 11756318 | Thus, the pool of IRS-1-associated PI 3-kinase activity is reduced, resulting in the inability of insulin to stimulate GLUT4 translocation to the plasma membrane. |
| 1726 | 11756327 | Phosphatidylinositol 3-kinase suppresses glucose-stimulated insulin secretion by affecting post-cytosolic [Ca(2+)] elevation signals. |
| 1727 | 11756327 | Insulin content and mass of rough endoplasmic reticula were decreased in beta-cells from p85 alpha(-/-) mice with increased insulin sensitivity. |
| 1728 | 11756327 | However, p85 alpha(-/-) beta-cells exhibited a marked increase in the insulin secretory response to higher concentrations of glucose. |
| 1729 | 11756339 | They had phosphorylation of the IGF-I receptor beta-subunit, phosphorylation of insulin receptor substrate (IRS)-1, and association of the p85 subunit (phosphatidylinositol 3-kinase [PI3K]) with the IGF-I receptor and IRS-1 in D-NOD cells in the basal state. |
| 1730 | 11756339 | Inhibiting autocrine IGF-I from binding to its receptor using an IGF-I-neutralizing antibody or inhibiting IGF-I signaling pathways using a specific PI3K inhibitor or a specific mitogen-activated protein kinase/extracellular response kinase kinase inhibitor decreased phosphorylated ERKs in D-NOD cells. |
| 1731 | 11756339 | They had phosphorylation of the IGF-I receptor beta-subunit, phosphorylation of insulin receptor substrate (IRS)-1, and association of the p85 subunit (phosphatidylinositol 3-kinase [PI3K]) with the IGF-I receptor and IRS-1 in D-NOD cells in the basal state. |
| 1732 | 11756339 | Inhibiting autocrine IGF-I from binding to its receptor using an IGF-I-neutralizing antibody or inhibiting IGF-I signaling pathways using a specific PI3K inhibitor or a specific mitogen-activated protein kinase/extracellular response kinase kinase inhibitor decreased phosphorylated ERKs in D-NOD cells. |
| 1733 | 11774095 | Moreover, leptin exerts several other important metabolic effects on peripheral tissue, including modification of insulin action, induction of angiogenesis, and modulation of the immune system. |
| 1734 | 11774095 | In glomerular endothelial cells, leptin stimulates cellular proliferation, transforming growth factor-beta1 (TGF-beta1) synthesis, and type IV collagen production. |
| 1735 | 11774095 | Conversely, in mesangial cells, leptin upregulates synthesis of the TGF-beta type II receptor, but not TGF-beta1, and stimulates glucose transport and type I collagen production through signal transduction pathways involving phosphatidylinositol-3-kinase. |
| 1736 | 11774095 | These data suggest that leptin triggers a paracrine interaction in which glomerular endothelial cells secrete TGF-beta, to which sensitized mesangial cells may respond. |
| 1737 | 11782951 | Regulation of cell size in growth, development and human disease: PI3K, PKB and S6K. |
| 1738 | 11782951 | Here we focus on two components of this pathway, PKB and S6K, and briefly review the experiments that initially uncovered their roles in cell size control. |
| 1739 | 11782951 | Finally, we have utilized two contemporary studies involving PKB- and S6K-deficient mice as a paradigm to underscore the importance of cell size and to accurately delineate the connections between signaling pathways for human disease, such as diabetes mellitus. |
| 1740 | 11788369 | No differences were found in tyrosine phosphorylation of the insulin receptor, insulin receptor substrate-1, and phosphatidylinositol 3-kinase among the groups. |
| 1741 | 11796489 | We show here that although insulin increased kappaB-dependent reporter gene expression and augmented nuclear translocation of the p65/RelA subunit of NFkappaB and its DNA binding, it was able to induce a time-dependent accumulation of phosphorylated and ubiquitinated IkappaBalpha without its proteolytic degradation. |
| 1742 | 11796489 | Immunofluorescence studies revealed the presence of a large pool of phosphorylated IkappaBalpha in the nucleus of unstimulated and insulin-treated cells. |
| 1743 | 11796489 | IkappaB kinase alpha and beta, central players in the phosphorylation of IkappaBalpha, were rapidly induced following exposure to TNFalpha but not insulin. |
| 1744 | 11796489 | Furthermore, insulin-stimulated IkappaBalpha phosphorylation did not depend on activation of the Ras/ERK cascade. |
| 1745 | 11796489 | Expression of a dominant-negative mutant of Akt1 or class I PI3K inhibited the insulin stimulation of PI3K/Akt1 signaling without affecting phosphorylation of IkappaBalpha. |
| 1746 | 11796489 | Interestingly, the PI3K inhibitors wortmannin and LY294002 blocked insulin-stimulated class I PI3K-dependent events at much lower doses than that required to inhibit phosphorylation of IkappaBalpha. |
| 1747 | 11796489 | These data demonstrate that insulin regulates IkappaBalpha function through a distinct low-affinity wortmannin-sensitive pathway. |
| 1748 | 11796489 | We show here that although insulin increased kappaB-dependent reporter gene expression and augmented nuclear translocation of the p65/RelA subunit of NFkappaB and its DNA binding, it was able to induce a time-dependent accumulation of phosphorylated and ubiquitinated IkappaBalpha without its proteolytic degradation. |
| 1749 | 11796489 | Immunofluorescence studies revealed the presence of a large pool of phosphorylated IkappaBalpha in the nucleus of unstimulated and insulin-treated cells. |
| 1750 | 11796489 | IkappaB kinase alpha and beta, central players in the phosphorylation of IkappaBalpha, were rapidly induced following exposure to TNFalpha but not insulin. |
| 1751 | 11796489 | Furthermore, insulin-stimulated IkappaBalpha phosphorylation did not depend on activation of the Ras/ERK cascade. |
| 1752 | 11796489 | Expression of a dominant-negative mutant of Akt1 or class I PI3K inhibited the insulin stimulation of PI3K/Akt1 signaling without affecting phosphorylation of IkappaBalpha. |
| 1753 | 11796489 | Interestingly, the PI3K inhibitors wortmannin and LY294002 blocked insulin-stimulated class I PI3K-dependent events at much lower doses than that required to inhibit phosphorylation of IkappaBalpha. |
| 1754 | 11796489 | These data demonstrate that insulin regulates IkappaBalpha function through a distinct low-affinity wortmannin-sensitive pathway. |
| 1755 | 11809761 | The protein serine/threonine kinase Akt/protein kinase B has been recognized as a critical signaling mediator for multiple cell systems. |
| 1756 | 11809761 | In addition to increasing phosphorylation, contraction in situ significantly increased the activity of all three Akt isoforms (Akt1 > Akt2 > Akt3) with maximal activation occurring at 2.5 min and returning to base line with 15 min of contraction. |
| 1757 | 11809761 | The phosphatidylinositol 3-kinase inhibitors wortmannin and LY294002 fully inhibited contraction-stimulated Akt phosphorylation and activity but did not diminish contraction-stimulated glycogen synthase kinase-3 phosphorylation and glycogen synthase activity. |
| 1758 | 11826398 | Insulin signaling in the transcriptional and posttranscriptional regulation of CYP2E1 expression. |
| 1759 | 11826398 | Diabetes has been reported to increase the expression of cytochrome P450 (CYP) 2E1 messenger RNA (mRNA) and protein several-fold, and enhanced expression has been associated with elevated ketone bodies. |
| 1760 | 11826398 | Primary cultured rat hepatocytes were used to explore ketone body and insulin regulation of CYP2E1 expression. |
| 1761 | 11826398 | Insulin produced a concentration-dependent decrease in CYP2E1 mRNA levels, and insulin receptor immunoprecipitation showed a correspondence between receptor phosphorylation and the decrease in CYP2E1 mRNA levels at physiologic levels of insulin. |
| 1762 | 11826398 | The phosphatidylinositol 3-kinase (PI3-kinase) inhibitors wortmannin or LY294002 and rapamycin, an inhibitor of p70 S6 kinase phosphorylation, ameliorated the insulin-mediated decrease in CYP2E1 mRNA levels. |
| 1763 | 11826398 | Geldanamycin, which inhibits Src kinase, also abrogated the insulin-mediated decrease in CYP2E1 mRNA levels. |
| 1764 | 11826398 | In contrast, the protein kinase C (PKC) inhibitor bisindolylmaleimide, the mitogen-activated protein kinase kinase (MEK) inhibitor PD98059, and the p38 mitogen-activated protein (MAP) kinase inhibitor SB202190 did not affect the insulin-mediated decrease in CYP2E1. |
| 1765 | 11826398 | CYP2E1 mRNA half-life decreased from approximately 48 hours in the absence of insulin to approximately 15 hours at 10 nmol/L insulin, and this decrease was prevented by wortmannin. |
| 1766 | 11826398 | The half-life of CYP2B mRNA was increased by insulin, whereas that of CYP3A was unaffected. |
| 1767 | 11826398 | Analysis of CYP2E1 gene transcription using heterogeneous nuclear RNA (hnRNA) showed that insulin suppressed CYP2E1 transcription. |
| 1768 | 11826398 | In conclusion, these data show involvement of transcriptional and posttranscriptional mechanisms in the insulin-mediated regulation of CYP2E1 and implicate PI3-kinase, p70 S6 kinase, and Src kinase in mediating these effects. |
| 1769 | 11832353 | Downregulated IRS-1 and PPARgamma in obese women with gestational diabetes: relationship to FFA during pregnancy. |
| 1770 | 11832353 | Adipose tissue insulin receptor substrate (IRS)-1 protein levels were 43% lower (P = 0.02) and p85alpha subunit of phosphatidylinositol 3-kinase was twofold higher (P = 0.03) in GDM compared with Preg-Con subjects. |
| 1771 | 11832353 | Lipoprotein lipase and fatty acid-binding protein-2 mRNA levels were 73 and 52% lower in GDM compared with Preg-Con subjects (P < 0.002). |
| 1772 | 11832353 | Thus GDM women have decreased IRS-1, which may contribute to reduced insulin suppression of lipolysis with advancing gestation. |
| 1773 | 11836310 | PKC-zeta mediates insulin effects on glucose transport in cultured preadipocyte-derived human adipocytes. |
| 1774 | 11836310 | Studies in rodent cells suggest that atypical PKC (aPKC) isoforms (zeta, lamda, and iota) and PKB, and their upstream activators, PI3K and 3-phosphoinositide-dependent protein kinase-1 (PDK-1), play important roles in insulin-stimulated glucose transport. |
| 1775 | 11836310 | However, there is no information on requirements for aPKCs, PKB, or PDK-1 during insulin action in human cell types. |
| 1776 | 11836310 | Expression of kinase-inactive forms of PDK-1, PKC-zeta, and PKC-lamda (which functions interchangeably with PKC-zeta) as well as chemical inhibitors of PI 3-kinase and PKC-zeta/lamda, wortmannin and the cell-permeable myristoylated PKC-zeta pseudosubstrate, respectively, effectively inhibited insulin-stimulated glucose transport. |
| 1777 | 11836310 | In contrast, expression of a kinase-inactive, activation-resistant, triple alanine mutant form of PKB-alpha had little or no effect, and expression of wild-type and constitutively active PKC-zeta or PKC-lamda increased glucose transport. |
| 1778 | 11836310 | Our findings provide convincing evidence that aPKCs and upstream activators, PI 3-kinase and PDK-1, play important roles in insulin-stimulated glucose transport in preadipocyte-derived human adipocytes. |
| 1779 | 11862760 | Using an antisense technique, PKC alpha and delta/epsilon were shown to be necessary for gene expression of inducible NO synthase by interleukin-1, one of the proinflammatory cytokines, by a stimulated transactivation of NF-kappa B (TH). |
| 1780 | 11862760 | In canine cerebral artery, PKC delta and PKC alpha play important roles in the development and the maintenance of vasospasm induced by subarachnoid hemorrhage, respectively (SN); and stretch-induced MLC20 phosphorylation involves MLCK and PKC alpha but not PKC delta activities facilitated by inactivation of myosin phosphatase through Rho activity (KO & KN). |
| 1781 | 11862760 | To clarify the role of PKC isozymes in insulin resistance, the effects of insulin on glucose uptake, PKC isozyme activation and PI3K activation in rat adipocytes were shown and then platelet PKC beta activation in diabetic patients with various diabetic complications, including diabetic retinopathy, was reported (TI). |
| 1782 | 11875115 | 14-3-3 facilitates insulin-stimulated intracellular trafficking of insulin receptor substrate 1. |
| 1783 | 11875115 | The appearance of a complex between tyrosine-phosphorylated insulin receptor substrate 1 (IRS-1) and PI3K in a high-speed pellet fraction (HSP) is thought to be a key event in insulin action. |
| 1784 | 11875115 | Conversely, the disappearance of the IRS-1/PI3K complex from this fraction has been linked to insulin desensitization. |
| 1785 | 11875115 | The present study examines the role of 14-3-3, a specific phospho-serine binding protein, in mediating the disappearance of IRS-1 from the HSP after insulin treatment. |
| 1786 | 11875115 | An in vitro pull-down assay using recombinant 14-3-3 revealed that insulin enhances the association of 14-3-3 with IRS-1 in cultured adipocytes and that this is completely inhibited by wortmannin. |
| 1787 | 11875115 | An association of IRS-1 and 14-3-3 was also observed and was maximal after stimulation by insulin, when endogenous proteins were immunoprecipitated. |
| 1788 | 11875115 | Epidermal growth factor (EGF), 12-O-tetradecanoylphorbol-13-acetate, and okadaic acid, other agents that cause serine/threonine phosphorylation of IRS-1, also stimulated IRS binding to 14-3-3. |
| 1789 | 11875115 | The enhancement of IRS-1 binding to 14-3-3 by insulin was accompanied by movement of IRS-1 and the p85 subunit of PI3K from the HSP to the cytosol. |
| 1790 | 11875115 | In keeping with a key role of 14-3-3 in mediating this redistribution of IRS-1, the complexes of IRS-1 and 14-3-3 were found in the cytosol but not in the HSP of insulin-treated cells. |
| 1791 | 11875115 | In addition, colocalization of IRS-1 and 14-3-3 was observed in the cytoplasm after insulin treatment by confocal microscopy. |
| 1792 | 11875115 | Finally, the addition of a phosphorylated 14-3-3 binding peptide to an adipocyte homogenate (to remove 14-3-3 from IRS-1) increased the abundance of IRS-1/PI3K complexes in the HSP and decreased their abundance in the cytosol. |
| 1793 | 11875115 | 14-3-3 facilitates insulin-stimulated intracellular trafficking of insulin receptor substrate 1. |
| 1794 | 11875115 | The appearance of a complex between tyrosine-phosphorylated insulin receptor substrate 1 (IRS-1) and PI3K in a high-speed pellet fraction (HSP) is thought to be a key event in insulin action. |
| 1795 | 11875115 | Conversely, the disappearance of the IRS-1/PI3K complex from this fraction has been linked to insulin desensitization. |
| 1796 | 11875115 | The present study examines the role of 14-3-3, a specific phospho-serine binding protein, in mediating the disappearance of IRS-1 from the HSP after insulin treatment. |
| 1797 | 11875115 | An in vitro pull-down assay using recombinant 14-3-3 revealed that insulin enhances the association of 14-3-3 with IRS-1 in cultured adipocytes and that this is completely inhibited by wortmannin. |
| 1798 | 11875115 | An association of IRS-1 and 14-3-3 was also observed and was maximal after stimulation by insulin, when endogenous proteins were immunoprecipitated. |
| 1799 | 11875115 | Epidermal growth factor (EGF), 12-O-tetradecanoylphorbol-13-acetate, and okadaic acid, other agents that cause serine/threonine phosphorylation of IRS-1, also stimulated IRS binding to 14-3-3. |
| 1800 | 11875115 | The enhancement of IRS-1 binding to 14-3-3 by insulin was accompanied by movement of IRS-1 and the p85 subunit of PI3K from the HSP to the cytosol. |
| 1801 | 11875115 | In keeping with a key role of 14-3-3 in mediating this redistribution of IRS-1, the complexes of IRS-1 and 14-3-3 were found in the cytosol but not in the HSP of insulin-treated cells. |
| 1802 | 11875115 | In addition, colocalization of IRS-1 and 14-3-3 was observed in the cytoplasm after insulin treatment by confocal microscopy. |
| 1803 | 11875115 | Finally, the addition of a phosphorylated 14-3-3 binding peptide to an adipocyte homogenate (to remove 14-3-3 from IRS-1) increased the abundance of IRS-1/PI3K complexes in the HSP and decreased their abundance in the cytosol. |
| 1804 | 11875115 | 14-3-3 facilitates insulin-stimulated intracellular trafficking of insulin receptor substrate 1. |
| 1805 | 11875115 | The appearance of a complex between tyrosine-phosphorylated insulin receptor substrate 1 (IRS-1) and PI3K in a high-speed pellet fraction (HSP) is thought to be a key event in insulin action. |
| 1806 | 11875115 | Conversely, the disappearance of the IRS-1/PI3K complex from this fraction has been linked to insulin desensitization. |
| 1807 | 11875115 | The present study examines the role of 14-3-3, a specific phospho-serine binding protein, in mediating the disappearance of IRS-1 from the HSP after insulin treatment. |
| 1808 | 11875115 | An in vitro pull-down assay using recombinant 14-3-3 revealed that insulin enhances the association of 14-3-3 with IRS-1 in cultured adipocytes and that this is completely inhibited by wortmannin. |
| 1809 | 11875115 | An association of IRS-1 and 14-3-3 was also observed and was maximal after stimulation by insulin, when endogenous proteins were immunoprecipitated. |
| 1810 | 11875115 | Epidermal growth factor (EGF), 12-O-tetradecanoylphorbol-13-acetate, and okadaic acid, other agents that cause serine/threonine phosphorylation of IRS-1, also stimulated IRS binding to 14-3-3. |
| 1811 | 11875115 | The enhancement of IRS-1 binding to 14-3-3 by insulin was accompanied by movement of IRS-1 and the p85 subunit of PI3K from the HSP to the cytosol. |
| 1812 | 11875115 | In keeping with a key role of 14-3-3 in mediating this redistribution of IRS-1, the complexes of IRS-1 and 14-3-3 were found in the cytosol but not in the HSP of insulin-treated cells. |
| 1813 | 11875115 | In addition, colocalization of IRS-1 and 14-3-3 was observed in the cytoplasm after insulin treatment by confocal microscopy. |
| 1814 | 11875115 | Finally, the addition of a phosphorylated 14-3-3 binding peptide to an adipocyte homogenate (to remove 14-3-3 from IRS-1) increased the abundance of IRS-1/PI3K complexes in the HSP and decreased their abundance in the cytosol. |
| 1815 | 11875115 | 14-3-3 facilitates insulin-stimulated intracellular trafficking of insulin receptor substrate 1. |
| 1816 | 11875115 | The appearance of a complex between tyrosine-phosphorylated insulin receptor substrate 1 (IRS-1) and PI3K in a high-speed pellet fraction (HSP) is thought to be a key event in insulin action. |
| 1817 | 11875115 | Conversely, the disappearance of the IRS-1/PI3K complex from this fraction has been linked to insulin desensitization. |
| 1818 | 11875115 | The present study examines the role of 14-3-3, a specific phospho-serine binding protein, in mediating the disappearance of IRS-1 from the HSP after insulin treatment. |
| 1819 | 11875115 | An in vitro pull-down assay using recombinant 14-3-3 revealed that insulin enhances the association of 14-3-3 with IRS-1 in cultured adipocytes and that this is completely inhibited by wortmannin. |
| 1820 | 11875115 | An association of IRS-1 and 14-3-3 was also observed and was maximal after stimulation by insulin, when endogenous proteins were immunoprecipitated. |
| 1821 | 11875115 | Epidermal growth factor (EGF), 12-O-tetradecanoylphorbol-13-acetate, and okadaic acid, other agents that cause serine/threonine phosphorylation of IRS-1, also stimulated IRS binding to 14-3-3. |
| 1822 | 11875115 | The enhancement of IRS-1 binding to 14-3-3 by insulin was accompanied by movement of IRS-1 and the p85 subunit of PI3K from the HSP to the cytosol. |
| 1823 | 11875115 | In keeping with a key role of 14-3-3 in mediating this redistribution of IRS-1, the complexes of IRS-1 and 14-3-3 were found in the cytosol but not in the HSP of insulin-treated cells. |
| 1824 | 11875115 | In addition, colocalization of IRS-1 and 14-3-3 was observed in the cytoplasm after insulin treatment by confocal microscopy. |
| 1825 | 11875115 | Finally, the addition of a phosphorylated 14-3-3 binding peptide to an adipocyte homogenate (to remove 14-3-3 from IRS-1) increased the abundance of IRS-1/PI3K complexes in the HSP and decreased their abundance in the cytosol. |
| 1826 | 11897556 | Phosphoinositide 3-kinase (PI3K) plays a key role in insulin signaling and has been shown to be blunted in tissues of type 2 diabetes subjects. |
| 1827 | 11897556 | There is emerging biochemical and, particularly, genetic evidence suggesting that insulin resistance can potentially be treated via modulation of PI3K by targeting PI3K itself or its up and down-stream modulators. |
| 1828 | 11897556 | These potential targets include Src homology 2 domain containing inositol 5-phosphatase 2 (SHIP2), phosphatase and tensin homolog deleted on chromosome ten (PTEN), kappaB kinase beta (IKKbeta), PKC isoforms, and the PI3K p85 subunit. |
| 1829 | 11897556 | There is evidence suggesting that their inhibition affects PI3K activity and improves insulin sensitivity in vivo. |
| 1830 | 11897556 | In the current review, we will discuss the role of these molecules in insulin-mediated activation of PI3K, the rational for targeting these molecules for diabetes treatment, and some critical issues in terms of drug development. |
| 1831 | 11897556 | Phosphoinositide 3-kinase (PI3K) plays a key role in insulin signaling and has been shown to be blunted in tissues of type 2 diabetes subjects. |
| 1832 | 11897556 | There is emerging biochemical and, particularly, genetic evidence suggesting that insulin resistance can potentially be treated via modulation of PI3K by targeting PI3K itself or its up and down-stream modulators. |
| 1833 | 11897556 | These potential targets include Src homology 2 domain containing inositol 5-phosphatase 2 (SHIP2), phosphatase and tensin homolog deleted on chromosome ten (PTEN), kappaB kinase beta (IKKbeta), PKC isoforms, and the PI3K p85 subunit. |
| 1834 | 11897556 | There is evidence suggesting that their inhibition affects PI3K activity and improves insulin sensitivity in vivo. |
| 1835 | 11897556 | In the current review, we will discuss the role of these molecules in insulin-mediated activation of PI3K, the rational for targeting these molecules for diabetes treatment, and some critical issues in terms of drug development. |
| 1836 | 11897556 | Phosphoinositide 3-kinase (PI3K) plays a key role in insulin signaling and has been shown to be blunted in tissues of type 2 diabetes subjects. |
| 1837 | 11897556 | There is emerging biochemical and, particularly, genetic evidence suggesting that insulin resistance can potentially be treated via modulation of PI3K by targeting PI3K itself or its up and down-stream modulators. |
| 1838 | 11897556 | These potential targets include Src homology 2 domain containing inositol 5-phosphatase 2 (SHIP2), phosphatase and tensin homolog deleted on chromosome ten (PTEN), kappaB kinase beta (IKKbeta), PKC isoforms, and the PI3K p85 subunit. |
| 1839 | 11897556 | There is evidence suggesting that their inhibition affects PI3K activity and improves insulin sensitivity in vivo. |
| 1840 | 11897556 | In the current review, we will discuss the role of these molecules in insulin-mediated activation of PI3K, the rational for targeting these molecules for diabetes treatment, and some critical issues in terms of drug development. |
| 1841 | 11897556 | Phosphoinositide 3-kinase (PI3K) plays a key role in insulin signaling and has been shown to be blunted in tissues of type 2 diabetes subjects. |
| 1842 | 11897556 | There is emerging biochemical and, particularly, genetic evidence suggesting that insulin resistance can potentially be treated via modulation of PI3K by targeting PI3K itself or its up and down-stream modulators. |
| 1843 | 11897556 | These potential targets include Src homology 2 domain containing inositol 5-phosphatase 2 (SHIP2), phosphatase and tensin homolog deleted on chromosome ten (PTEN), kappaB kinase beta (IKKbeta), PKC isoforms, and the PI3K p85 subunit. |
| 1844 | 11897556 | There is evidence suggesting that their inhibition affects PI3K activity and improves insulin sensitivity in vivo. |
| 1845 | 11897556 | In the current review, we will discuss the role of these molecules in insulin-mediated activation of PI3K, the rational for targeting these molecules for diabetes treatment, and some critical issues in terms of drug development. |
| 1846 | 11897556 | Phosphoinositide 3-kinase (PI3K) plays a key role in insulin signaling and has been shown to be blunted in tissues of type 2 diabetes subjects. |
| 1847 | 11897556 | There is emerging biochemical and, particularly, genetic evidence suggesting that insulin resistance can potentially be treated via modulation of PI3K by targeting PI3K itself or its up and down-stream modulators. |
| 1848 | 11897556 | These potential targets include Src homology 2 domain containing inositol 5-phosphatase 2 (SHIP2), phosphatase and tensin homolog deleted on chromosome ten (PTEN), kappaB kinase beta (IKKbeta), PKC isoforms, and the PI3K p85 subunit. |
| 1849 | 11897556 | There is evidence suggesting that their inhibition affects PI3K activity and improves insulin sensitivity in vivo. |
| 1850 | 11897556 | In the current review, we will discuss the role of these molecules in insulin-mediated activation of PI3K, the rational for targeting these molecules for diabetes treatment, and some critical issues in terms of drug development. |
| 1851 | 11914736 | The majority of the islet-restricted (BETA2, PDX-1, RIP3b1-Act/C1) and ubiquitous (E2A, HEB) insulin-binding proteins have been characterized. |
| 1852 | 11914736 | Their DNA binding activity and their transactivating potency can be modified in response to nutrients (glucose, NEFA) or hormonal stimuli (insulin, leptin, glucagon like peptide-1, growth hormone, prolactin) through kinase-dependent signalling pathways (PI3-K, p38MAPK, PKA, CaMK) modulating their affinities for DNA and/or for each other. |
| 1853 | 11916914 | Activation of IRS-2-mediated signal transduction by IGF-1, but not TGF-alpha or EGF, augments pancreatic beta-cell proliferation. |
| 1854 | 11916914 | Transforming growth factor (TGF)-alpha- and epidermal growth factor (EGF)-induced signal transduction was directly compared with that of glucose and insulin-like growth factor-1 (IGF-1) in INS-1 cells. |
| 1855 | 11916914 | TGF-alpha/EGF transiently (<20 min) induced phosphorylation of extracellular-regulated kinase (Erk)-1/2 (>20-fold), glycogen synthase kinase (GSK)-3 (>10-fold), and protein kinase B (PKB) (Ser(473) and Thr(308)), but did not increase [(3)H]thymidine incorporation. |
| 1856 | 11916914 | In contrast, phosphorylation of Erk1/2, GSK-3, and PKB in response to glucose and IGF-1 was more prolonged (>24 h) and, though not as robust as TGF-alpha/EGF, did increase beta-cell proliferation. |
| 1857 | 11916914 | Phosphorylation of p70(S6K) was also increased by IGF-1/glucose, but not by TGF-alpha/EGF, despite upstream PKB activation. |
| 1858 | 11916914 | It was found that IGF-1 induced phosphatidylinositol 3-kinase (PI3K) association with insulin receptor substrate (IRS)-1 and -2 in a glucose-dependent manner, whereas TGF-alpha/EGF did not. |
| 1859 | 11916914 | The importance of specific IRS-2-mediated signaling events was emphasized in that adenoviral-mediated overexpression of IRS-2 further increased glucose/IGF-1-induced beta-cell proliferation (more than twofold; P < 0.05) compared with control or adenoviral-mediated IRS-1 overexpressing INS-1 cells. |
| 1860 | 11916914 | Neither IRS-1 nor IRS-2 overexpression induced a beta-cell proliferative response to TGF-alpha/EGF. |
| 1861 | 11916914 | Thus, a prolonged activation of Erk1/2 and PI3K signaling pathways is important in committing a beta-cell to a mitogenic event, and it is likely that this sustained activation is instigated by signal transduction occurring specifically through IRS-2. |
| 1862 | 11916914 | Activation of IRS-2-mediated signal transduction by IGF-1, but not TGF-alpha or EGF, augments pancreatic beta-cell proliferation. |
| 1863 | 11916914 | Transforming growth factor (TGF)-alpha- and epidermal growth factor (EGF)-induced signal transduction was directly compared with that of glucose and insulin-like growth factor-1 (IGF-1) in INS-1 cells. |
| 1864 | 11916914 | TGF-alpha/EGF transiently (<20 min) induced phosphorylation of extracellular-regulated kinase (Erk)-1/2 (>20-fold), glycogen synthase kinase (GSK)-3 (>10-fold), and protein kinase B (PKB) (Ser(473) and Thr(308)), but did not increase [(3)H]thymidine incorporation. |
| 1865 | 11916914 | In contrast, phosphorylation of Erk1/2, GSK-3, and PKB in response to glucose and IGF-1 was more prolonged (>24 h) and, though not as robust as TGF-alpha/EGF, did increase beta-cell proliferation. |
| 1866 | 11916914 | Phosphorylation of p70(S6K) was also increased by IGF-1/glucose, but not by TGF-alpha/EGF, despite upstream PKB activation. |
| 1867 | 11916914 | It was found that IGF-1 induced phosphatidylinositol 3-kinase (PI3K) association with insulin receptor substrate (IRS)-1 and -2 in a glucose-dependent manner, whereas TGF-alpha/EGF did not. |
| 1868 | 11916914 | The importance of specific IRS-2-mediated signaling events was emphasized in that adenoviral-mediated overexpression of IRS-2 further increased glucose/IGF-1-induced beta-cell proliferation (more than twofold; P < 0.05) compared with control or adenoviral-mediated IRS-1 overexpressing INS-1 cells. |
| 1869 | 11916914 | Neither IRS-1 nor IRS-2 overexpression induced a beta-cell proliferative response to TGF-alpha/EGF. |
| 1870 | 11916914 | Thus, a prolonged activation of Erk1/2 and PI3K signaling pathways is important in committing a beta-cell to a mitogenic event, and it is likely that this sustained activation is instigated by signal transduction occurring specifically through IRS-2. |
| 1871 | 11916922 | Signaling through the phosphatidylinositol 3'-kinase (PI3K) pathway is crucial for metabolic responses to insulin, and defects in PI3K signaling have been demonstrated in type 2 diabetes. |
| 1872 | 11916922 | PTEN (MMAC1) is a lipid/protein phosphatase that can negatively regulate the PI3K pathway by dephosphorylating phosphatidylinositol (3,4,5)-triphosphate, but it is unclear whether PTEN is physiologically relevant to insulin signaling in vivo. |
| 1873 | 11916922 | Transfection of cells in culture with ASO targeting PTEN reduced PTEN mRNA and protein levels and increased insulin-stimulated Akt phosphorylation in alpha-mouse liver-12 (AML12) cells. |
| 1874 | 11916922 | Inhibition of PTEN expression also dramatically reduced insulin concentrations in ob/ob mice, improved the performance of db/db mice during insulin tolerance tests, and increased Akt phosphorylation in liver in response to insulin. |
| 1875 | 11916922 | These results suggest that PTEN plays a significant role in regulating glucose metabolism in vivo by negatively regulating insulin signaling. |
| 1876 | 11916922 | Signaling through the phosphatidylinositol 3'-kinase (PI3K) pathway is crucial for metabolic responses to insulin, and defects in PI3K signaling have been demonstrated in type 2 diabetes. |
| 1877 | 11916922 | PTEN (MMAC1) is a lipid/protein phosphatase that can negatively regulate the PI3K pathway by dephosphorylating phosphatidylinositol (3,4,5)-triphosphate, but it is unclear whether PTEN is physiologically relevant to insulin signaling in vivo. |
| 1878 | 11916922 | Transfection of cells in culture with ASO targeting PTEN reduced PTEN mRNA and protein levels and increased insulin-stimulated Akt phosphorylation in alpha-mouse liver-12 (AML12) cells. |
| 1879 | 11916922 | Inhibition of PTEN expression also dramatically reduced insulin concentrations in ob/ob mice, improved the performance of db/db mice during insulin tolerance tests, and increased Akt phosphorylation in liver in response to insulin. |
| 1880 | 11916922 | These results suggest that PTEN plays a significant role in regulating glucose metabolism in vivo by negatively regulating insulin signaling. |
| 1881 | 11919188 | A Forkhead/winged helix-related transcription factor mediates insulin-increased plasminogen activator inhibitor-1 gene transcription. |
| 1882 | 11919188 | Insulin increases PAI-1 production in several experimental systems, but the mechanism of insulin-activated PAI-1 transcription remains to be determined. |
| 1883 | 11919188 | Deletion analysis of the PAI-1 promoter revealed that the insulin response element is between -117 and -7. |
| 1884 | 11919188 | Mutation of the AT-rich site at -52/-45 abolished the insulin responsiveness of the PAI-1 promoter. |
| 1885 | 11919188 | Gel-mobility shift assays demonstrated that the forkhead bound to the PAI-1 promoter insulin response element. |
| 1886 | 11919188 | Expression of the DNA-binding domain of FKHR acted as a dominant negative to block insulin-increased PAI-1-CAT expression. |
| 1887 | 11919188 | These data suggested that a member of the Forkhead/winged helix family of transcription factors mediated the effect of insulin on PAI-1 transcription. |
| 1888 | 11919188 | Inhibition of phosphatidylinositol 3-kinase reduced the effect of insulin on PAI-1 gene expression, a result consistent with activation through FKHR. |
| 1889 | 11919188 | However, it was likely that a different member of the FKHR family (not FKHR) mediated this effect since FKHR was present in both insulin-responsive and non-responsive cell lines. |
| 1890 | 11922615 | However, in contrast to insulin, shikonin-stimulated glucose uptake was not strongly inhibited by wortmannin, a specific inhibitor of phosphatidylinositol 3-kinase (PI3K). |
| 1891 | 11922615 | In vitro phosphorylation analyses revealed that shikonin did not induce tyrosine phosphorylation of the insulin receptor, but significantly induced both Thr-308 and Ser-473 phosphorylation of Akt. |
| 1892 | 11922615 | Our results suggest that in 3T3-L1 adipocytes, shikonin action is not mediated primarily via the insulin receptor/PI3K pathway, but rather via another distinct tyrosine kinase-dependent pathway leading to glucose uptake involving Akt phosphorylation. |
| 1893 | 11922615 | However, in contrast to insulin, shikonin-stimulated glucose uptake was not strongly inhibited by wortmannin, a specific inhibitor of phosphatidylinositol 3-kinase (PI3K). |
| 1894 | 11922615 | In vitro phosphorylation analyses revealed that shikonin did not induce tyrosine phosphorylation of the insulin receptor, but significantly induced both Thr-308 and Ser-473 phosphorylation of Akt. |
| 1895 | 11922615 | Our results suggest that in 3T3-L1 adipocytes, shikonin action is not mediated primarily via the insulin receptor/PI3K pathway, but rather via another distinct tyrosine kinase-dependent pathway leading to glucose uptake involving Akt phosphorylation. |
| 1896 | 11964395 | The steady-state levels of PEPCK and glucose-6-phosphatase mRNAs were elevated in livers of TG mice and were resistant to down-regulation by insulin. |
| 1897 | 11964395 | Conversely, GLUT2 and glucokinase mRNA levels were appropriately regulated by insulin, suggesting that insulin resistance is selective to gluconeogenic gene expression. |
| 1898 | 11964395 | Insulin-stimulated phosphorylation of the insulin receptor, insulin receptor substrate (IRS)-1, and associated phosphatidylinositol 3-kinase were normal in TG mice, whereas IRS-2 protein and phosphorylation were down-regulated compared with control mice. |
| 1899 | 11964395 | Furthermore, these results demonstrate that PEPCK overexpression results in a metabolic pattern that increases glucose-6-phosphatase mRNA and results in a selective decrease in IRS-2 protein, decreased phosphatidylinositol 3-kinase activity, and reduced ability of insulin to suppress gluconeogenic gene expression. |
| 1900 | 11964395 | However, acute suppression of HGP and glycolytic gene expression remained intact, suggesting that FFA and/or IRS-1 signaling, in addition to reduced IRS-2, plays an important role in downstream insulin signal transduction pathways involved in control of gluconeogenesis and progression to type II diabetes mellitus. |
| 1901 | 11964395 | The steady-state levels of PEPCK and glucose-6-phosphatase mRNAs were elevated in livers of TG mice and were resistant to down-regulation by insulin. |
| 1902 | 11964395 | Conversely, GLUT2 and glucokinase mRNA levels were appropriately regulated by insulin, suggesting that insulin resistance is selective to gluconeogenic gene expression. |
| 1903 | 11964395 | Insulin-stimulated phosphorylation of the insulin receptor, insulin receptor substrate (IRS)-1, and associated phosphatidylinositol 3-kinase were normal in TG mice, whereas IRS-2 protein and phosphorylation were down-regulated compared with control mice. |
| 1904 | 11964395 | Furthermore, these results demonstrate that PEPCK overexpression results in a metabolic pattern that increases glucose-6-phosphatase mRNA and results in a selective decrease in IRS-2 protein, decreased phosphatidylinositol 3-kinase activity, and reduced ability of insulin to suppress gluconeogenic gene expression. |
| 1905 | 11964395 | However, acute suppression of HGP and glycolytic gene expression remained intact, suggesting that FFA and/or IRS-1 signaling, in addition to reduced IRS-2, plays an important role in downstream insulin signal transduction pathways involved in control of gluconeogenesis and progression to type II diabetes mellitus. |
| 1906 | 11978789 | Glucagon-like peptide-2 receptor activation engages bad and glycogen synthase kinase-3 in a protein kinase A-dependent manner and prevents apoptosis following inhibition of phosphatidylinositol 3-kinase. |
| 1907 | 11978789 | We now demonstrate that GLP-2, in a cycloheximide-insensitive manner, enhanced survival in baby hamster kidney cells stably transfected with the rat GLP-2R; reduced mitochondrial cytochrome c efflux; and attenuated the caspase-dependent cleavage of Akt, poly(ADP-ribose) polymerase, and beta-catenin following inhibition of phosphatidylinositol 3-kinase (PI3K) by LY294002. |
| 1908 | 11978789 | The prosurvival effects of GLP-2 on LY294002-induced cell death were independent of Akt, p90(Rsk), or p70 S6 kinase activation; were mimicked by forskolin; and were abrogated by inhibition of protein kinase A (PKA) activity. |
| 1909 | 11978789 | GLP-2 inhibited activation of glycogen synthase kinase-3 (GSK-3) through phosphorylation at Ser(21) in GSK-3alpha and at Ser(9) in GSK-3beta in a PI3K-independent, PKA-dependent manner. |
| 1910 | 11978789 | GLP-2 reduced LY294002-induced mitochondrial association of endogenous Bad and Bax and stimulated phosphorylation of a transfected Bad fusion protein at Ser(155) in a PI3K-independent, but H89-sensitive manner, a modification known to suppress Bad pro-apoptotic activity. |
| 1911 | 11978789 | These results suggest that GLP-2R signaling enhances cell survival independently of PI3K/Akt by inhibiting the activity of a subset of pro-apoptotic downstream targets of Akt in a PKA-dependent manner. |
| 1912 | 11978789 | Glucagon-like peptide-2 receptor activation engages bad and glycogen synthase kinase-3 in a protein kinase A-dependent manner and prevents apoptosis following inhibition of phosphatidylinositol 3-kinase. |
| 1913 | 11978789 | We now demonstrate that GLP-2, in a cycloheximide-insensitive manner, enhanced survival in baby hamster kidney cells stably transfected with the rat GLP-2R; reduced mitochondrial cytochrome c efflux; and attenuated the caspase-dependent cleavage of Akt, poly(ADP-ribose) polymerase, and beta-catenin following inhibition of phosphatidylinositol 3-kinase (PI3K) by LY294002. |
| 1914 | 11978789 | The prosurvival effects of GLP-2 on LY294002-induced cell death were independent of Akt, p90(Rsk), or p70 S6 kinase activation; were mimicked by forskolin; and were abrogated by inhibition of protein kinase A (PKA) activity. |
| 1915 | 11978789 | GLP-2 inhibited activation of glycogen synthase kinase-3 (GSK-3) through phosphorylation at Ser(21) in GSK-3alpha and at Ser(9) in GSK-3beta in a PI3K-independent, PKA-dependent manner. |
| 1916 | 11978789 | GLP-2 reduced LY294002-induced mitochondrial association of endogenous Bad and Bax and stimulated phosphorylation of a transfected Bad fusion protein at Ser(155) in a PI3K-independent, but H89-sensitive manner, a modification known to suppress Bad pro-apoptotic activity. |
| 1917 | 11978789 | These results suggest that GLP-2R signaling enhances cell survival independently of PI3K/Akt by inhibiting the activity of a subset of pro-apoptotic downstream targets of Akt in a PKA-dependent manner. |
| 1918 | 11978789 | Glucagon-like peptide-2 receptor activation engages bad and glycogen synthase kinase-3 in a protein kinase A-dependent manner and prevents apoptosis following inhibition of phosphatidylinositol 3-kinase. |
| 1919 | 11978789 | We now demonstrate that GLP-2, in a cycloheximide-insensitive manner, enhanced survival in baby hamster kidney cells stably transfected with the rat GLP-2R; reduced mitochondrial cytochrome c efflux; and attenuated the caspase-dependent cleavage of Akt, poly(ADP-ribose) polymerase, and beta-catenin following inhibition of phosphatidylinositol 3-kinase (PI3K) by LY294002. |
| 1920 | 11978789 | The prosurvival effects of GLP-2 on LY294002-induced cell death were independent of Akt, p90(Rsk), or p70 S6 kinase activation; were mimicked by forskolin; and were abrogated by inhibition of protein kinase A (PKA) activity. |
| 1921 | 11978789 | GLP-2 inhibited activation of glycogen synthase kinase-3 (GSK-3) through phosphorylation at Ser(21) in GSK-3alpha and at Ser(9) in GSK-3beta in a PI3K-independent, PKA-dependent manner. |
| 1922 | 11978789 | GLP-2 reduced LY294002-induced mitochondrial association of endogenous Bad and Bax and stimulated phosphorylation of a transfected Bad fusion protein at Ser(155) in a PI3K-independent, but H89-sensitive manner, a modification known to suppress Bad pro-apoptotic activity. |
| 1923 | 11978789 | These results suggest that GLP-2R signaling enhances cell survival independently of PI3K/Akt by inhibiting the activity of a subset of pro-apoptotic downstream targets of Akt in a PKA-dependent manner. |
| 1924 | 11978789 | Glucagon-like peptide-2 receptor activation engages bad and glycogen synthase kinase-3 in a protein kinase A-dependent manner and prevents apoptosis following inhibition of phosphatidylinositol 3-kinase. |
| 1925 | 11978789 | We now demonstrate that GLP-2, in a cycloheximide-insensitive manner, enhanced survival in baby hamster kidney cells stably transfected with the rat GLP-2R; reduced mitochondrial cytochrome c efflux; and attenuated the caspase-dependent cleavage of Akt, poly(ADP-ribose) polymerase, and beta-catenin following inhibition of phosphatidylinositol 3-kinase (PI3K) by LY294002. |
| 1926 | 11978789 | The prosurvival effects of GLP-2 on LY294002-induced cell death were independent of Akt, p90(Rsk), or p70 S6 kinase activation; were mimicked by forskolin; and were abrogated by inhibition of protein kinase A (PKA) activity. |
| 1927 | 11978789 | GLP-2 inhibited activation of glycogen synthase kinase-3 (GSK-3) through phosphorylation at Ser(21) in GSK-3alpha and at Ser(9) in GSK-3beta in a PI3K-independent, PKA-dependent manner. |
| 1928 | 11978789 | GLP-2 reduced LY294002-induced mitochondrial association of endogenous Bad and Bax and stimulated phosphorylation of a transfected Bad fusion protein at Ser(155) in a PI3K-independent, but H89-sensitive manner, a modification known to suppress Bad pro-apoptotic activity. |
| 1929 | 11978789 | These results suggest that GLP-2R signaling enhances cell survival independently of PI3K/Akt by inhibiting the activity of a subset of pro-apoptotic downstream targets of Akt in a PKA-dependent manner. |
| 1930 | 11978789 | Glucagon-like peptide-2 receptor activation engages bad and glycogen synthase kinase-3 in a protein kinase A-dependent manner and prevents apoptosis following inhibition of phosphatidylinositol 3-kinase. |
| 1931 | 11978789 | We now demonstrate that GLP-2, in a cycloheximide-insensitive manner, enhanced survival in baby hamster kidney cells stably transfected with the rat GLP-2R; reduced mitochondrial cytochrome c efflux; and attenuated the caspase-dependent cleavage of Akt, poly(ADP-ribose) polymerase, and beta-catenin following inhibition of phosphatidylinositol 3-kinase (PI3K) by LY294002. |
| 1932 | 11978789 | The prosurvival effects of GLP-2 on LY294002-induced cell death were independent of Akt, p90(Rsk), or p70 S6 kinase activation; were mimicked by forskolin; and were abrogated by inhibition of protein kinase A (PKA) activity. |
| 1933 | 11978789 | GLP-2 inhibited activation of glycogen synthase kinase-3 (GSK-3) through phosphorylation at Ser(21) in GSK-3alpha and at Ser(9) in GSK-3beta in a PI3K-independent, PKA-dependent manner. |
| 1934 | 11978789 | GLP-2 reduced LY294002-induced mitochondrial association of endogenous Bad and Bax and stimulated phosphorylation of a transfected Bad fusion protein at Ser(155) in a PI3K-independent, but H89-sensitive manner, a modification known to suppress Bad pro-apoptotic activity. |
| 1935 | 11978789 | These results suggest that GLP-2R signaling enhances cell survival independently of PI3K/Akt by inhibiting the activity of a subset of pro-apoptotic downstream targets of Akt in a PKA-dependent manner. |
| 1936 | 12031952 | Role of the insulin receptor substrate 1 and phosphatidylinositol 3-kinase signaling pathway in insulin-induced expression of sterol regulatory element binding protein 1c and glucokinase genes in rat hepatocytes. |
| 1937 | 12031952 | The mechanism by which insulin induces the expression of the sterol regulatory element binding protein 1c (SREBP-1c) and glucokinase genes was investigated in cultured rat hepatocytes. |
| 1938 | 12031952 | Overexpression of an NH(2)-terminal fragment of IRS-1 that contains the pleckstrin homology and phosphotyrosine binding domains (insulin receptor substrate-1 NH(2)-terminal fragment [IRS-1N]) inhibited insulin-induced tyrosine phosphorylation of IRS-1 as well as the association of IRS-1 with phosphatidylinositol (PI) 3-kinase activity, whereas the tyrosine phosphorylation of IRS-2 and its association with PI 3-kinase activity were slightly enhanced. |
| 1939 | 12031952 | The equivalent fragment of IRS-2 (IRS-2N) prevented insulin-induced tyrosine phosphorylation of both IRS-1 and IRS-2, although that of IRS-1 was inhibited more efficiently. |
| 1940 | 12031952 | The insulin-induced increases in the abundance of SREBP-1c and glucokinase mRNAs, both of which were sensitive to a dominant-negative mutant of PI 3-kinase, were blocked in cells in which the insulin-induced tyrosine phosphorylation of IRS-1 was inhibited by IRS-1N or IRS-2N. |
| 1941 | 12031952 | A dominant-negative mutant of Akt enhanced insulin-induced tyrosine phosphorylation of IRS-1 (but not that of IRS-2) and its association with PI 3-kinase activity, suggesting that Akt contributes to negative feedback regulation of IRS-1. |
| 1942 | 12031952 | The Akt mutant also promoted the effects of insulin on the accumulation of SREBP-1c and glucokinase mRNAs. |
| 1943 | 12031952 | These results suggest that the IRS-1-PI 3-kinase pathway is essential for insulin-induced expression of SREBP-1c and glucokinase genes. |
| 1944 | 12031982 | Differential effects of tumor necrosis factor-alpha on protein kinase C isoforms alpha and delta mediate inhibition of insulin receptor signaling. |
| 1945 | 12031982 | Tumor necrosis factor-alpha (TNF-alpha) is a multifunctional cytokine that interferes with insulin signaling, but the molecular mechanisms of this effect are unclear. |
| 1946 | 12031982 | Because certain protein kinase C (PKC) isoforms are activated by insulin, we examined the role of PKC in TNF-alpha inhibition of insulin signaling in primary cultures of mouse skeletal muscle. |
| 1947 | 12031982 | TNF-alpha, given 5 min before insulin, inhibited insulin-induced tyrosine phosphorylation of insulin receptor (IR), IR substrate (IRS)-1, insulin-induced association of IRS-1 with the p85 subunit of phosphatidylinositol 3-kinase (PI3-K), and insulin-induced glucose uptake. |
| 1948 | 12031982 | Insulin and TNF-alpha each caused tyrosine phosphorylation and activation of PKCs delta and alpha, but when TNF-alpha preceded insulin, the effects were less than that produced by each substance alone. |
| 1949 | 12031982 | Insulin induced PKCdelta specifically to coprecipitate with IR, an effect blocked by TNF-alpha. |
| 1950 | 12031982 | Both PKCalpha and -delta are constitutively associated with IRS-1. |
| 1951 | 12031982 | Whereas insulin decreased coprecipitation of IRS-1 with PKCalpha, it increased coprecipitation of IRS-1 with PKCdelta. |
| 1952 | 12031982 | TNF-alpha blocked the effects of insulin on association of both PKCs with IRS-1. |
| 1953 | 12031982 | To further investigate the involvement of PKCs in inhibitory actions of TNF-alpha on insulin signaling, we overexpressed specific PKC isoforms in mature myotubes. |
| 1954 | 12031982 | PKCalpha overexpression inhibited basal and insulin-induced IR autophosphorylation, whereas PKCdelta overexpression increased IR autophosphorylation and abrogated the inhibitory effect of TNF-alpha on IR autophosphorylation and signaling to PI3-K. |
| 1955 | 12031982 | Blockade of PKCalpha antagonized the inhibitory effects of TNF-alpha on both insulin-induced IR tyrosine phosphorylation and IR signaling to PI3-K. |
| 1956 | 12031982 | We suggest that the effects of TNF-alpha on IR tyrosine phosphorylation are mediated via alteration of insulin-induced activation and association of PKCdelta and -alpha with upstream signaling molecules. |
| 1957 | 12031982 | Differential effects of tumor necrosis factor-alpha on protein kinase C isoforms alpha and delta mediate inhibition of insulin receptor signaling. |
| 1958 | 12031982 | Tumor necrosis factor-alpha (TNF-alpha) is a multifunctional cytokine that interferes with insulin signaling, but the molecular mechanisms of this effect are unclear. |
| 1959 | 12031982 | Because certain protein kinase C (PKC) isoforms are activated by insulin, we examined the role of PKC in TNF-alpha inhibition of insulin signaling in primary cultures of mouse skeletal muscle. |
| 1960 | 12031982 | TNF-alpha, given 5 min before insulin, inhibited insulin-induced tyrosine phosphorylation of insulin receptor (IR), IR substrate (IRS)-1, insulin-induced association of IRS-1 with the p85 subunit of phosphatidylinositol 3-kinase (PI3-K), and insulin-induced glucose uptake. |
| 1961 | 12031982 | Insulin and TNF-alpha each caused tyrosine phosphorylation and activation of PKCs delta and alpha, but when TNF-alpha preceded insulin, the effects were less than that produced by each substance alone. |
| 1962 | 12031982 | Insulin induced PKCdelta specifically to coprecipitate with IR, an effect blocked by TNF-alpha. |
| 1963 | 12031982 | Both PKCalpha and -delta are constitutively associated with IRS-1. |
| 1964 | 12031982 | Whereas insulin decreased coprecipitation of IRS-1 with PKCalpha, it increased coprecipitation of IRS-1 with PKCdelta. |
| 1965 | 12031982 | TNF-alpha blocked the effects of insulin on association of both PKCs with IRS-1. |
| 1966 | 12031982 | To further investigate the involvement of PKCs in inhibitory actions of TNF-alpha on insulin signaling, we overexpressed specific PKC isoforms in mature myotubes. |
| 1967 | 12031982 | PKCalpha overexpression inhibited basal and insulin-induced IR autophosphorylation, whereas PKCdelta overexpression increased IR autophosphorylation and abrogated the inhibitory effect of TNF-alpha on IR autophosphorylation and signaling to PI3-K. |
| 1968 | 12031982 | Blockade of PKCalpha antagonized the inhibitory effects of TNF-alpha on both insulin-induced IR tyrosine phosphorylation and IR signaling to PI3-K. |
| 1969 | 12031982 | We suggest that the effects of TNF-alpha on IR tyrosine phosphorylation are mediated via alteration of insulin-induced activation and association of PKCdelta and -alpha with upstream signaling molecules. |
| 1970 | 12031982 | Differential effects of tumor necrosis factor-alpha on protein kinase C isoforms alpha and delta mediate inhibition of insulin receptor signaling. |
| 1971 | 12031982 | Tumor necrosis factor-alpha (TNF-alpha) is a multifunctional cytokine that interferes with insulin signaling, but the molecular mechanisms of this effect are unclear. |
| 1972 | 12031982 | Because certain protein kinase C (PKC) isoforms are activated by insulin, we examined the role of PKC in TNF-alpha inhibition of insulin signaling in primary cultures of mouse skeletal muscle. |
| 1973 | 12031982 | TNF-alpha, given 5 min before insulin, inhibited insulin-induced tyrosine phosphorylation of insulin receptor (IR), IR substrate (IRS)-1, insulin-induced association of IRS-1 with the p85 subunit of phosphatidylinositol 3-kinase (PI3-K), and insulin-induced glucose uptake. |
| 1974 | 12031982 | Insulin and TNF-alpha each caused tyrosine phosphorylation and activation of PKCs delta and alpha, but when TNF-alpha preceded insulin, the effects were less than that produced by each substance alone. |
| 1975 | 12031982 | Insulin induced PKCdelta specifically to coprecipitate with IR, an effect blocked by TNF-alpha. |
| 1976 | 12031982 | Both PKCalpha and -delta are constitutively associated with IRS-1. |
| 1977 | 12031982 | Whereas insulin decreased coprecipitation of IRS-1 with PKCalpha, it increased coprecipitation of IRS-1 with PKCdelta. |
| 1978 | 12031982 | TNF-alpha blocked the effects of insulin on association of both PKCs with IRS-1. |
| 1979 | 12031982 | To further investigate the involvement of PKCs in inhibitory actions of TNF-alpha on insulin signaling, we overexpressed specific PKC isoforms in mature myotubes. |
| 1980 | 12031982 | PKCalpha overexpression inhibited basal and insulin-induced IR autophosphorylation, whereas PKCdelta overexpression increased IR autophosphorylation and abrogated the inhibitory effect of TNF-alpha on IR autophosphorylation and signaling to PI3-K. |
| 1981 | 12031982 | Blockade of PKCalpha antagonized the inhibitory effects of TNF-alpha on both insulin-induced IR tyrosine phosphorylation and IR signaling to PI3-K. |
| 1982 | 12031982 | We suggest that the effects of TNF-alpha on IR tyrosine phosphorylation are mediated via alteration of insulin-induced activation and association of PKCdelta and -alpha with upstream signaling molecules. |
| 1983 | 12086937 | Sustained exposure of L6 myotubes to high glucose and insulin decreases insulin-stimulated GLUT4 translocation but upregulates GLUT4 activity. |
| 1984 | 12086937 | In adipose cell cultures, high glucose and insulin cause insulin resistance of glucose uptake, but because of altered GLUT4 expression and contribution of GLUT1 to glucose uptake, the basis of insulin resistance could not be ascertained. |
| 1985 | 12086937 | Preincubation for 24 h with high glucose and insulin (high Glc/Ins) reduced insulin-stimulated GLUT4 translocation by 50%, without affecting GLUT4 expression. |
| 1986 | 12086937 | Insulin receptor and insulin receptor substrate-1 tyrosine phosphorylation, phosphatidylinositol 3-kinase activation, and Akt phosphorylation also diminished, as did insulin-mediated glucose uptake. |
| 1987 | 12086937 | High Glc/Ins elevated basal p38 mitogen-activated protein kinase (MAPK) phosphorylation and activity, and a short inhibition of p38 MAPK with SB202190 corrected the rise in basal glucose uptake, suggesting that p38 MAPK activity contributes to this rise. |
| 1988 | 12086937 | We propose that in a cellular model of skeletal muscle, chronic exposure to high Glc/Ins reduced the acute, insulin-elicited GLUT4 translocation. |
| 1989 | 12086960 | Our results demonstrate that JAK2, insulin receptor substrate (IRS)-1, Shc, ERKs, and Akt are widely distributed in the kidney, and after GH treatment, there is a significant increase in phosphorylation of these proteins in STZ-induced diabetic rats compared with controls. |
| 1990 | 12086960 | Moreover, the GH-induced association of IRS-1/phosphatidylinositol 3-kinase, IRS-1/growth factor receptor bound 2 (Grb2), and Shc/Grb2 are increased in diabetic rats as well. |
| 1991 | 12095990 | Fatty acid infusion selectively impairs insulin action on Akt1 and protein kinase C lambda /zeta but not on glycogen synthase kinase-3. |
| 1992 | 12095990 | To determine the mechanism(s) for insulin resistance induced by fatty acids, we measured the ability of insulin to activate phosphoinositide 3-kinase (PI3K) and multiple distal pathways in rats. |
| 1993 | 12095990 | Insulin stimulated IRS-1-associated PI3K activity in muscle of glycerol-infused rats 2.4-fold but had no effect in lipid-infused rats. |
| 1994 | 12095990 | IRS-2- and phosphotyrosine-associated PI3K activity were increased 3.5- and 4.8-fold, respectively, by insulin in glycerol-infused rats but only 1.6- and 2.3-fold in lipid-infused rats. |
| 1995 | 12095990 | Insulin increased Akt1 activity 3.9-fold in glycerol-infused rats, and this was impaired 41% in lipid-infused rats. |
| 1996 | 12095990 | Insulin action on Akt2 and p70S6K were not impaired, whereas activation of protein kinase C lambda/zeta activity was reduced 47%. |
| 1997 | 12095990 | Insulin inhibited glycogen synthase kinase 3alpha (GSK-3alpha) activity by 30% and GSK-3beta activity by approximately 65% and increased protein phosphatase-1 activity by 40-47% in both glycerol- and lipid-infused rats. |
| 1998 | 12095990 | Thus, 1) elevation of fatty acids differentially affects insulin action on pathways distal to PI3K, impairing activation of Akt1 and protein kinase C lambda/zeta and 2) insulin action on glycogen synthase can be regulated independent of effects on GSK-3 and protein phosphatase-1 activity in vivo. |
| 1999 | 12095990 | Fatty acid infusion selectively impairs insulin action on Akt1 and protein kinase C lambda /zeta but not on glycogen synthase kinase-3. |
| 2000 | 12095990 | To determine the mechanism(s) for insulin resistance induced by fatty acids, we measured the ability of insulin to activate phosphoinositide 3-kinase (PI3K) and multiple distal pathways in rats. |
| 2001 | 12095990 | Insulin stimulated IRS-1-associated PI3K activity in muscle of glycerol-infused rats 2.4-fold but had no effect in lipid-infused rats. |
| 2002 | 12095990 | IRS-2- and phosphotyrosine-associated PI3K activity were increased 3.5- and 4.8-fold, respectively, by insulin in glycerol-infused rats but only 1.6- and 2.3-fold in lipid-infused rats. |
| 2003 | 12095990 | Insulin increased Akt1 activity 3.9-fold in glycerol-infused rats, and this was impaired 41% in lipid-infused rats. |
| 2004 | 12095990 | Insulin action on Akt2 and p70S6K were not impaired, whereas activation of protein kinase C lambda/zeta activity was reduced 47%. |
| 2005 | 12095990 | Insulin inhibited glycogen synthase kinase 3alpha (GSK-3alpha) activity by 30% and GSK-3beta activity by approximately 65% and increased protein phosphatase-1 activity by 40-47% in both glycerol- and lipid-infused rats. |
| 2006 | 12095990 | Thus, 1) elevation of fatty acids differentially affects insulin action on pathways distal to PI3K, impairing activation of Akt1 and protein kinase C lambda/zeta and 2) insulin action on glycogen synthase can be regulated independent of effects on GSK-3 and protein phosphatase-1 activity in vivo. |
| 2007 | 12095990 | Fatty acid infusion selectively impairs insulin action on Akt1 and protein kinase C lambda /zeta but not on glycogen synthase kinase-3. |
| 2008 | 12095990 | To determine the mechanism(s) for insulin resistance induced by fatty acids, we measured the ability of insulin to activate phosphoinositide 3-kinase (PI3K) and multiple distal pathways in rats. |
| 2009 | 12095990 | Insulin stimulated IRS-1-associated PI3K activity in muscle of glycerol-infused rats 2.4-fold but had no effect in lipid-infused rats. |
| 2010 | 12095990 | IRS-2- and phosphotyrosine-associated PI3K activity were increased 3.5- and 4.8-fold, respectively, by insulin in glycerol-infused rats but only 1.6- and 2.3-fold in lipid-infused rats. |
| 2011 | 12095990 | Insulin increased Akt1 activity 3.9-fold in glycerol-infused rats, and this was impaired 41% in lipid-infused rats. |
| 2012 | 12095990 | Insulin action on Akt2 and p70S6K were not impaired, whereas activation of protein kinase C lambda/zeta activity was reduced 47%. |
| 2013 | 12095990 | Insulin inhibited glycogen synthase kinase 3alpha (GSK-3alpha) activity by 30% and GSK-3beta activity by approximately 65% and increased protein phosphatase-1 activity by 40-47% in both glycerol- and lipid-infused rats. |
| 2014 | 12095990 | Thus, 1) elevation of fatty acids differentially affects insulin action on pathways distal to PI3K, impairing activation of Akt1 and protein kinase C lambda/zeta and 2) insulin action on glycogen synthase can be regulated independent of effects on GSK-3 and protein phosphatase-1 activity in vivo. |
| 2015 | 12095990 | Fatty acid infusion selectively impairs insulin action on Akt1 and protein kinase C lambda /zeta but not on glycogen synthase kinase-3. |
| 2016 | 12095990 | To determine the mechanism(s) for insulin resistance induced by fatty acids, we measured the ability of insulin to activate phosphoinositide 3-kinase (PI3K) and multiple distal pathways in rats. |
| 2017 | 12095990 | Insulin stimulated IRS-1-associated PI3K activity in muscle of glycerol-infused rats 2.4-fold but had no effect in lipid-infused rats. |
| 2018 | 12095990 | IRS-2- and phosphotyrosine-associated PI3K activity were increased 3.5- and 4.8-fold, respectively, by insulin in glycerol-infused rats but only 1.6- and 2.3-fold in lipid-infused rats. |
| 2019 | 12095990 | Insulin increased Akt1 activity 3.9-fold in glycerol-infused rats, and this was impaired 41% in lipid-infused rats. |
| 2020 | 12095990 | Insulin action on Akt2 and p70S6K were not impaired, whereas activation of protein kinase C lambda/zeta activity was reduced 47%. |
| 2021 | 12095990 | Insulin inhibited glycogen synthase kinase 3alpha (GSK-3alpha) activity by 30% and GSK-3beta activity by approximately 65% and increased protein phosphatase-1 activity by 40-47% in both glycerol- and lipid-infused rats. |
| 2022 | 12095990 | Thus, 1) elevation of fatty acids differentially affects insulin action on pathways distal to PI3K, impairing activation of Akt1 and protein kinase C lambda/zeta and 2) insulin action on glycogen synthase can be regulated independent of effects on GSK-3 and protein phosphatase-1 activity in vivo. |
| 2023 | 12138086 | Epidermal growth factor and transforming growth factor alpha mimic the effects of insulin in human fat cells and augment downstream signaling in insulin resistance. |
| 2024 | 12138086 | The ability of the growth factors epidermal growth factor (EGF), transforming growth factor alpha, and platelet-derived growth factor to exert insulin-like effects on glucose transport and lipolysis were examined in human and rat fat cells. |
| 2025 | 12138086 | No effects were found in rat fat cells, whereas EGF (EC(50) for glucose transport approximately 0.02 nm) and transforming growth factor alpha (EC(50) approximately 0.2 nm), but not platelet-derived growth factor, mimicked the effects of insulin (EC(50) approximately 0.2 nm) on both pathways. |
| 2026 | 12138086 | EGF increased the tyrosine phosphorylation of several proteins (the EGF receptor, insulin receptor substrate (IRS)-1, IRS-2, and Grb2-associated binder 1), whereas Shc and Gab2 were only weakly and inconsistently phosphorylated. p85, the regulatory subunit of phosphatidylinositol 3-kinase (PI 3-kinase), was also found to associate with all of these docking molecules, showing that EGF activated PI 3-kinase pools that were additional to those of insulin. |
| 2027 | 12138086 | EGF and/or insulin increased protein kinase B/Akt serine phosphorylation to a similar extent, whereas mitogen-activated protein kinase phosphorylation was more pronounced for EGF than for insulin. |
| 2028 | 12138086 | The impaired insulin-stimulated downstream signaling, measured as protein kinase B/Akt serine phosphorylation, in insulin-resistant cells (Type 2 diabetes) was improved by the addition of EGF. |
| 2029 | 12138086 | EGF mimics the effects of insulin on both the metabolic and mitogenic pathways but utilize in part different signaling pathways. |
| 2030 | 12138086 | Both insulin and EGF increase the tyrosine phosphorylation and activation of IRS-1 and IRS-2, whereas EGF is also capable of activating additional PI 3-kinase pools and, thus, can augment the downstream signaling of insulin in insulin-resistant states like Type 2 diabetes. |
| 2031 | 12145151 | Protein tyrosine phosphatase 1B (PTP1B) has been implicated as a negative regulator of insulin action. |
| 2032 | 12145151 | Overexpression of PTP1B protein has been observed in insulin-resistant states associated with obesity. |
| 2033 | 12145151 | Mice lacking a functional PTP1B gene exhibit increased insulin sensitivity and are resistant to weight gain. |
| 2034 | 12145151 | Antisense treatment also influenced the triglyceride content in adipocytes, correlating with a downregulation of genes encoding proteins involved in lipogenesis, such as sterol regulatory element-binding protein 1 and their downstream targets spot14 and fatty acid synthase, as well as other adipogenic genes, lipoprotein lipase, and peroxisome proliferator-activated receptor gamma. |
| 2035 | 12145151 | In addition, an increase in insulin receptor substrate-2 protein and a differential regulation of the phosphatidylinositol 3-kinase regulatory subunit (p85alpha) isoforms expression were found in fat from antisense-treated animals, although increased insulin sensitivity measured by protein kinase B phosphorylation was not observed. |
| 2036 | 12145151 | These results demonstrate that PTP1B antisense treatment can modulate fat storage and lipogenesis in adipose tissue and might implicate PTP1B in the enlargement of adipocyte energy stores and development of obesity. |
| 2037 | 12166618 | Regulation of IRS-1/SHP2 interaction and AKT phosphorylation in animal models of insulin resistance. |
| 2038 | 12166618 | Insulin stimulates tyrosine kinase activity of its receptor, resulting in phosphorylation of its cytosolic substrate, insulin receptor substrate-1, which, in turn, associates with proteins containing SH2 domains, including phosphatidylinositol 3-kinase (PI 3-kinase) and the phosphotyrosine phosphatase SHP2. |
| 2039 | 12166618 | In the present study, we investigated insulin-induced IRS-1/SHP2 and IRS-1/PI 3-kinase associations and the regulation of a downstream serine-kinase AKT/PKB in liver and muscle of three animal models of insulin resistance: STZ diabetes, epinephrine-treated rats, and aging, which have alterations in IRS-1 tyrosine phosphorylation in common. |
| 2040 | 12166618 | The results demonstrated that insulin-induced IRS-1/PI 3-kinase association has a close correlation with IRS-1 tyrosine phosphorylation levels, but insulin-induced IRS-1/SHP2 association showed a modulation that did not parallel IRS-1 phosphorylation, with a tissue-specific regulation in aging. |
| 2041 | 12166618 | The integration of the behavior of IRS-1/PI 3-kinase and with IRS-1/SHP2 associations may be important for insulin signaling downstream as AKT phosphorylation. |
| 2042 | 12166618 | In conclusion, the results of the present study demonstrated that insulin-induced IRS-1/SHP2 association can be regulated in insulin-sensitive tissues of animal models of insulin resistance and may have a role in the control of AKT phosphorylation, which may be implicated in the control of glucose metabolism. |
| 2043 | 12179956 | Activation of phosphatidylinositol 3-kinase (PI3-K) is utilized by insulin to induce glucose transporter translocation, but does not participate in the responses to exercise or hypoxia. |
| 2044 | 12196460 | In the biopsies, insulin receptor kinase (IRK) activity, insulin receptor substrate (IRS)-1-associated phosphatidylinositol 3-kinase (PI3K) activity, Ser(473) and Thr(308) phosphorylation of protein kinase B (PKB), and protein expression of IRS-1, IRS-2, phosphoinositol-dependent kinase-1 (PDK-1), PKB, and GLUT-4 were determined. |
| 2045 | 12196460 | IRK and PI3K activities were not altered by troglitazone, but PKB Ser(473) phosphorylation was enhanced compared with pretreatment and placebo at the clamp insulin level (138 +/- 36 vs. 77 +/- 16 and 55 +/- 13 internal standard units; both P < 0.05) and with pretreatment at the basal level (31 +/- 9 vs. 14 +/- 4 internal standard units; P < 0.05). |
| 2046 | 12196460 | Troglitazone did not alter insulin receptor number or IRS-1, IRS-2, PKB, PDK-1, or GLUT-4 protein expression. |
| 2047 | 12196460 | We conclude that increased PKB phosphorylation may contribute to the insulin-sensitizing effects of thiazolidinediones in human skeletal muscle. |
| 2048 | 12196460 | In the biopsies, insulin receptor kinase (IRK) activity, insulin receptor substrate (IRS)-1-associated phosphatidylinositol 3-kinase (PI3K) activity, Ser(473) and Thr(308) phosphorylation of protein kinase B (PKB), and protein expression of IRS-1, IRS-2, phosphoinositol-dependent kinase-1 (PDK-1), PKB, and GLUT-4 were determined. |
| 2049 | 12196460 | IRK and PI3K activities were not altered by troglitazone, but PKB Ser(473) phosphorylation was enhanced compared with pretreatment and placebo at the clamp insulin level (138 +/- 36 vs. 77 +/- 16 and 55 +/- 13 internal standard units; both P < 0.05) and with pretreatment at the basal level (31 +/- 9 vs. 14 +/- 4 internal standard units; P < 0.05). |
| 2050 | 12196460 | Troglitazone did not alter insulin receptor number or IRS-1, IRS-2, PKB, PDK-1, or GLUT-4 protein expression. |
| 2051 | 12196460 | We conclude that increased PKB phosphorylation may contribute to the insulin-sensitizing effects of thiazolidinediones in human skeletal muscle. |
| 2052 | 12205083 | Western blotting revealed that dopamine increased the association of dynamin-2 with the plasma membrane and with phosphatidylinositol 3-kinase. |
| 2053 | 12205083 | Dopamine increased protein phosphatase 2A activity and dephosphorylated dynamin-2. |
| 2054 | 12205083 | In cells expressing a dominant-negative mutant of protein phosphatase 2A, dopamine failed to dephosphorylate dynamin-2 and to reduce Na(+),K(+)-ATPase activity. |
| 2055 | 12205083 | These results demonstrate a distinct signaling network originating from the dopamine receptor that regulates the state of dynamin-2 phosphorylation and that promotes its location (by interaction with phosphatidylinositol 3-kinase) at the site of Na(+),K(+)-ATPase endocytosis. |
| 2056 | 12205083 | Western blotting revealed that dopamine increased the association of dynamin-2 with the plasma membrane and with phosphatidylinositol 3-kinase. |
| 2057 | 12205083 | Dopamine increased protein phosphatase 2A activity and dephosphorylated dynamin-2. |
| 2058 | 12205083 | In cells expressing a dominant-negative mutant of protein phosphatase 2A, dopamine failed to dephosphorylate dynamin-2 and to reduce Na(+),K(+)-ATPase activity. |
| 2059 | 12205083 | These results demonstrate a distinct signaling network originating from the dopamine receptor that regulates the state of dynamin-2 phosphorylation and that promotes its location (by interaction with phosphatidylinositol 3-kinase) at the site of Na(+),K(+)-ATPase endocytosis. |
| 2060 | 12208734 | Cellular invasion induced by 10 ng/ml stem cell factor (EC(50) = 3 ng/ml) in HT29 cells was blocked by 1 micro M STI571 (IC(50) = 56 nM) and pharmacological inhibitors of several oncogenic signaling pathways, namely, phosphatidylinositol 3-kinase (LY294002), Rho GTPases (Clostridium botulinum exoenzyme C3 transferase), and Rho-kinase (Y27632). |
| 2061 | 12231074 | Defects in muscle glycogen synthesis play a significant role in insulin resistance, and 3 potentially rate-controlling steps in muscle glucose metabolism have been implicated in its pathogenesis: glycogen synthase, hexokinase, and GLUT4 (the major insulin-stimulated glucose transporter). |
| 2062 | 12231074 | These alterations in glucose transport activity are likely the result of dysregulation of intramyocellular fatty acid metabolism, whereby fatty acids cause insulin resistance by activation of a serine kinase cascade, leading to decreased insulin-stimulated insulin receptor substrate (IRS)-1 tyrosine phosphorylation and decreased IRS-1-associated phosphatidylinositol 3-kinase activity, a required step in insulin-stimulated glucose transport into muscle. |
| 2063 | 12231075 | In the context of insulin resistance, insulin has reduced effects on the phosphatidylinositol 3 kinase (PI3K) pathway, whereas mitogen-activated protein kinase activity is maintained. |
| 2064 | 12231075 | The result is an exaggeration of the mitogenic actions of insulin leading to vascular smooth muscle proliferation and elevated plasminogen activator inhibitor (PAI)-1. |
| 2065 | 12231075 | Patients who are insulin resistant have decreased fibrinolysis, as indicated by increased levels of PAI-1. |
| 2066 | 12351658 | One mechanism mediating insulin resistance may involve the phosphorylation of serine residues in insulin receptor substrate-1 (IRS-1), leading to impairment in the ability of IRS-1 to activate downstream phosphatidylinositol 3-kinase-dependent pathways. |
| 2067 | 12351658 | Insulin-resistant states and serine phosphorylation of IRS-1 are associated with the activation of the inhibitor kappaB kinase (IKK) complex. |
| 2068 | 12351658 | In this study, using phosphospecific antibodies against rat IRS-1 phosphorylated at Ser(307) (equivalent to Ser(312) in human IRS-1), we observed serine phosphorylation of IRS-1 in response to TNF-alpha or calyculin A treatment that paralleled surrogate markers for IKK activation. |
| 2069 | 12351658 | The phosphorylation of human IRS-1 at Ser(312) in response to tumor necrosis factor-alpha was significantly reduced in cells pretreated with the IKK inhibitor 15 deoxy-prostaglandin J(2) as well as in cells derived from IKK knock-out mice. |
| 2070 | 12351658 | Taken together, our data suggest that IRS-1 is a novel direct substrate for IKK and that phosphorylation of IRS-1 at Ser(312) (and other sites) by IKK may contribute to the insulin resistance mediated by activation of inflammatory pathways. |
| 2071 | 12397383 | Gene expression of the p85alpha regulatory subunit of phosphatidylinositol 3-kinase in skeletal muscle from type 2 diabetic subjects. |
| 2072 | 12397383 | PI 3-kinase activity in skeletal muscle following in vitro insulin stimulation was reduced in subjects with type 2 diabetes. p85alpha mRNA was elevated fourfold in type 2 diabetic as compared to healthy control subjects ( P<0.05). p85alpha mRNA abundance was positively correlated with plasma insulin concentration ( P<0.01) and serum glucose concentration ( P<0.01). |
| 2073 | 12397383 | Despite this, protein levels of p85alpha, p55alpha, and the novel human p50alpha were not altered in type 2 diabetic subjects. |
| 2074 | 12403787 | Hepatocyte growth factor (HGF) increases beta cell proliferation and function in rat insulin promoter (RIP)-targeted transgenic mice. |
| 2075 | 12403787 | Activation of the phosphatidylinositol 3-kinase/Akt intracellular-signaling pathway appeared to be involved in this beta cell protective effect of HGF in vitro. |
| 2076 | 12409500 | Gliclazide increases insulin receptor tyrosine phosphorylation but not p38 phosphorylation in insulin-resistant skeletal muscle cells. |
| 2077 | 12409500 | Although insulin receptor substrate-1 tyrosine phosphorylation was unaffected by gliclazide treatment, phosphatidylinositol 3-kinase activity was partially restored by treatment with gliclazide. |
| 2078 | 12409500 | Further investigations into the mitogen-activated protein kinase (MAPK) pathway revealed that insulin-stimulated p38 phosphorylation was impaired, as compared with extracellular-signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK), which were phosphorylated normally in insulin-resistant cells. |
| 2079 | 12409500 | Treatment with gliclazide could not restore p38 phosphorylation in insulin-resistant cells. |
| 2080 | 12409500 | We propose that gliclazide can regulate part of the insulin signaling in insulin-resistant skeletal muscle, and p38 could be a potential therapeutic target for glucose uptake to treat insulin resistance. |
| 2081 | 12411472 | Leptin induces endothelial cell migration through Akt, which is inhibited by PPARgamma-ligands. |
| 2082 | 12411472 | The antidiabetic thiazolidinediones (TZD) inhibit leptin gene expression and vascular smooth muscle cell migration through activation of the peroxisome proliferator-activated receptor-gamma (PPARgamma). |
| 2083 | 12411472 | Because activation of two signaling pathways, the phosphatidylinositol-3 kinase (PI3K)-->Akt-->eNOS and the ERK1/2 MAPK pathway, is known to be involved in cell migration, we used the pharmacological inhibitors wortmannin and PD98059 to determine if chemotactic signaling by leptin involves Akt or ERK1/2, respectively. |
| 2084 | 12411472 | Treatment with the TZD-PPARgamma-ligands TRO and CIG significantly inhibited the chemotactic response toward leptin. |
| 2085 | 12411472 | Both PPARgamma-ligands inhibited leptin-stimulated Akt and eNOS phosphorylation, but neither attenuated ERK 1/2 activation in response to leptin. |
| 2086 | 12411472 | The inhibition of Akt-phosphorylation was accompanied by a PPARgamma-ligand-mediated upregulation of PTEN, a phosphatase that functions as a negative regulator of PI3K-->Akt signaling. |
| 2087 | 12411472 | These experiments provide the first evidence that activation of Akt and ERK 1/2 are crucial events in leptin-mediated signal transduction leading to EC migration. |
| 2088 | 12411472 | Moreover, inhibition of leptin-directed migration by the PPARgamma-ligands TRO and CIG through inhibition of Akt underscores their potential in the prevention of diabetes-associated complications. |
| 2089 | 12417588 | c-Jun N-terminal kinase (JNK) mediates feedback inhibition of the insulin signaling cascade. |
| 2090 | 12417588 | Activation of the c-Jun N-terminal kinase (JNK) by proinflammatory cytokines inhibits insulin signaling, at least in part, by stimulating phosphorylation of rat/mouse insulin receptor substrate 1 (Irs1) at Ser(307) (Ser(312) in human IRS1). |
| 2091 | 12417588 | Here we show that JNK mediated feedback inhibition of the insulin signal in mouse embryo fibroblasts, 3T3-L1 adipocytes, and 32D(IR) cells. |
| 2092 | 12417588 | Insulin stimulation of JNK activity required phosphatidylinositol 3-kinase and Grb2 signaling. |
| 2093 | 12417588 | Moreover, activation of JNK by insulin was inhibited by a cell-permeable peptide that disrupted the interaction of JNK with cellular proteins. |
| 2094 | 12417588 | However, the direct binding of JNK to Irs1 was not required for its activation by insulin, whereas direct binding was required for Ser(307) phosphorylation of Irs1. |
| 2095 | 12417588 | Insulin-stimulated Ser(307) phosphorylation was reduced 80% in cells lacking JNK1 and JNK2 or in cells expressing a mutant Irs1 protein lacking the JNK binding site. |
| 2096 | 12417588 | Reduced Ser(307) phosphorylation was directly related to increased insulin-stimulated tyrosine phosphorylation, Akt phosphorylation, and glucose uptake. |
| 2097 | 12417588 | These results support the hypothesis that JNK is a negative feedback regulator of insulin action by phosphorylating Ser(307) in Irs1. |
| 2098 | 12424101 | Here, released insulin initiates signal transduction cascades, principally through the activity of phosphatidylinositol 3-kinase. |
| 2099 | 12429837 | pp60Src mediates insulin-stimulated sequestration of the beta(2)-adrenergic receptor: insulin stimulates pp60Src phosphorylation and activation. |
| 2100 | 12429837 | Insulin stimulates a rapid phosphorylation and sequestration of the beta(2)-adrenergic receptor. |
| 2101 | 12429837 | Analysis of the signaling downstream of the insulin receptor with enzyme inhibitors revealed roles for both phosphatidylinositol 3-kinase and pp60Src. |
| 2102 | 12429837 | Inhibition of Src with PP2, like the inhibition of phosphatidylinositol 3-kinase with LY294002 [2-(4-morpholynyl)-8-phenyl-4H-1-benzopyran-4-one], blocked the activation of Src as well as insulin-stimulated sequestration of the beta(2)-adrenergic receptor. |
| 2103 | 12429837 | Inhibition of Src with PP2 blocks the ability of insulin to sequester beta(2)-adrenergic receptors and the translocation of the GLUT4 glucose transporters. |
| 2104 | 12429837 | Insulin stimulates Src to associate with the beta(2)-adrenergic receptor/AKAP250/protein kinase A/protein kinase C signaling complex. |
| 2105 | 12429837 | We report a novel positioning of Src, mediating signals from insulin to phosphatidylinositol 3-kinase and to beta(2)-adrenergic receptor trafficking. |
| 2106 | 12429837 | pp60Src mediates insulin-stimulated sequestration of the beta(2)-adrenergic receptor: insulin stimulates pp60Src phosphorylation and activation. |
| 2107 | 12429837 | Insulin stimulates a rapid phosphorylation and sequestration of the beta(2)-adrenergic receptor. |
| 2108 | 12429837 | Analysis of the signaling downstream of the insulin receptor with enzyme inhibitors revealed roles for both phosphatidylinositol 3-kinase and pp60Src. |
| 2109 | 12429837 | Inhibition of Src with PP2, like the inhibition of phosphatidylinositol 3-kinase with LY294002 [2-(4-morpholynyl)-8-phenyl-4H-1-benzopyran-4-one], blocked the activation of Src as well as insulin-stimulated sequestration of the beta(2)-adrenergic receptor. |
| 2110 | 12429837 | Inhibition of Src with PP2 blocks the ability of insulin to sequester beta(2)-adrenergic receptors and the translocation of the GLUT4 glucose transporters. |
| 2111 | 12429837 | Insulin stimulates Src to associate with the beta(2)-adrenergic receptor/AKAP250/protein kinase A/protein kinase C signaling complex. |
| 2112 | 12429837 | We report a novel positioning of Src, mediating signals from insulin to phosphatidylinositol 3-kinase and to beta(2)-adrenergic receptor trafficking. |
| 2113 | 12429837 | pp60Src mediates insulin-stimulated sequestration of the beta(2)-adrenergic receptor: insulin stimulates pp60Src phosphorylation and activation. |
| 2114 | 12429837 | Insulin stimulates a rapid phosphorylation and sequestration of the beta(2)-adrenergic receptor. |
| 2115 | 12429837 | Analysis of the signaling downstream of the insulin receptor with enzyme inhibitors revealed roles for both phosphatidylinositol 3-kinase and pp60Src. |
| 2116 | 12429837 | Inhibition of Src with PP2, like the inhibition of phosphatidylinositol 3-kinase with LY294002 [2-(4-morpholynyl)-8-phenyl-4H-1-benzopyran-4-one], blocked the activation of Src as well as insulin-stimulated sequestration of the beta(2)-adrenergic receptor. |
| 2117 | 12429837 | Inhibition of Src with PP2 blocks the ability of insulin to sequester beta(2)-adrenergic receptors and the translocation of the GLUT4 glucose transporters. |
| 2118 | 12429837 | Insulin stimulates Src to associate with the beta(2)-adrenergic receptor/AKAP250/protein kinase A/protein kinase C signaling complex. |
| 2119 | 12429837 | We report a novel positioning of Src, mediating signals from insulin to phosphatidylinositol 3-kinase and to beta(2)-adrenergic receptor trafficking. |
| 2120 | 12453887 | Identification of the insulin-regulated interaction of phosphodiesterase 3B with 14-3-3 beta protein. |
| 2121 | 12453887 | Insulin-induced phosphorylation and activation of PDE3B is phosphatidylinositol 3-kinase (PI3-K) and Akt dependent, but the precise mechanism of PDE3B activation is not fully understood. |
| 2122 | 12453887 | The glutathione S-transferase (GST)-tagged 14-3-3 beta interacts with endogenous PDE3B of rat adipocytes, and this interaction is enhanced when adipocytes are treated with insulin. |
| 2123 | 12453887 | Synthetic 15 amino acid peptides of rat PDE3B containing phosphorylated Ser-279 or -302 inhibit this interaction, indicating that the insulin-regulated phosphorylation of these serine residues is involved. |
| 2124 | 12453887 | Because insulin receptor substrate-1 also associates with 14-3-3, the dimeric 14-3-3 beta could function as a scaffolding protein in the activation of PDE3B by insulin. |
| 2125 | 12453891 | Interleukin-6 induces cellular insulin resistance in hepatocytes. |
| 2126 | 12453891 | Interleukin (IL)-6 is one of several proinflammatory cytokines that have been associated with insulin resistance and type 2 diabetes. |
| 2127 | 12453891 | Nonetheless, little evidence supports a direct role for IL-6 in mediating insulin resistance. |
| 2128 | 12453891 | Here, we present data that IL-6 can inhibit insulin receptor (IR) signal transduction and insulin action in both primary mouse hepatocytes and the human hepatocarcinoma cell line, HepG2. |
| 2129 | 12453891 | The IL-6 effect is characterized by a decreased tyrosine phosphorylation of IR substrate (IRS)-1 and decreased association of the p85 subunit of phosphatidylinositol 3-kinase with IRS-1 in response to physiologic insulin levels. |
| 2130 | 12453891 | In addition, insulin-dependent activation of Akt, important in mediating insulin's downstream metabolic actions, is markedly inhibited by IL-6 treatment. |
| 2131 | 12453891 | Finally, a 1.5-h preincubation of primary hepatocytes with IL-6 inhibits insulin-induced glycogen synthesis by 75%. |
| 2132 | 12453891 | These data suggest that IL-6 plays a direct role in insulin resistance at the cellular level in both primary hepatocytes and HepG2 cell lines and may contribute to insulin resistance and type 2 diabetes. |
| 2133 | 12496137 | Effects of AICAR and exercise on insulin-stimulated glucose uptake, signaling, and GLUT-4 content in rat muscles. |
| 2134 | 12496137 | Physical activity is known to increase insulin action in skeletal muscle, and data have indicated that 5'-AMP-activated protein kinase (AMPK) is involved in the molecular mechanisms behind this beneficial effect. 5-Aminoimidazole-4-carboxamide-1-beta-d-ribofuranoside (AICAR) can be used as a pharmacological tool to repetitively activate AMPK, and the objective of this study was to explore whether the increase in insulin-stimulated glucose uptake after either long-term exercise or chronic AICAR administration was followed by fiber-type-specific changes in insulin signaling and/or changes in GLUT-4 expression. |
| 2135 | 12496137 | AMPK activity, insulin-stimulated glucose transport, insulin signaling, and GLUT-4 expression were determined in muscles characterized by different fiber type compositions. |
| 2136 | 12496137 | Insulin signaling as assessed by phosphatidylinositol 3-kinase and PKB/Akt activity was enhanced only after AICAR administration and in a non-fiber-type-specific manner. |
| 2137 | 12496137 | In conclusion, chronic AICAR administration and long-term exercise both improve insulin-stimulated glucose transport in skeletal muscle in a fiber-type-specific way, and this is associated with an increase in GLUT-4 content. |
| 2138 | 12502490 | Dietary cod protein restores insulin-induced activation of phosphatidylinositol 3-kinase/Akt and GLUT4 translocation to the T-tubules in skeletal muscle of high-fat-fed obese rats. |
| 2139 | 12502490 | Insulin-induced tyrosine phosphorylation of the insulin receptor and insulin receptor substrate (IRS) proteins were similar in muscle of chow- and high-fat-fed rats regardless of the dietary protein source. |
| 2140 | 12502490 | The activation of the downstream kinase Akt/PKB by insulin, assessed by in vitro kinase assay and phosphorylation of GSK-3beta, were also impaired in muscle of high-fat-fed rats consuming casein or soy protein, but these defects were also fully prevented by dietary cod protein. |
| 2141 | 12502490 | Normalization of PI 3-kinase/Akt activation by insulin in rats fed high-fat diets with cod protein was associated with improved translocation of GLUT4 to the T-tubules but not to the plasma membrane. |
| 2142 | 12502490 | Taken together, these results show that dietary cod protein is a natural insulin-sensitizing agent that appears to prevent obesity-linked muscle insulin resistance by normalizing insulin activation of the PI 3-kinase/Akt pathway and by selectively improving GLUT4 translocation to the T-tubules. |
| 2143 | 12502492 | Differential regulation of lipogenesis and leptin production by independent signaling pathways and rosiglitazone during human adipocyte differentiation. |
| 2144 | 12502492 | We used inhibitors of p70(S6) kinase, p42/44 mitogen-activated protein kinase (MAPK), p38 MAPK, and phosphatidylinositol 3-kinase (PI3K). |
| 2145 | 12502492 | Human preadipocytes were induced to differentiate in insulin, dexamethasone, triiodothyronine, and 3-isobutyl-1-methylxanthine in the presence or absence of inhibitors and the peroxisome proliferator-activated receptor (PPAR)-gamma activator rosiglitazone. |
| 2146 | 12502492 | None of the inhibitors significantly inhibited protein content over 20 days, but lipid content and lipogenic activity were inhibited by p70(S6) kinase and p38 MAPK inhibition but not by p42/44 MAPK or PI3K inhibition. |
| 2147 | 12502492 | We conclude that PI3K and p42/44 MAPK pathways are not critical to the differentiation program leading to lipid accumulation, but stimulation of leptin secretion is dependent on these as well as the p70(S6) kinase and p38 MAPK signaling pathways. |
| 2148 | 12502492 | Differential regulation of lipogenesis and leptin production by independent signaling pathways and rosiglitazone during human adipocyte differentiation. |
| 2149 | 12502492 | We used inhibitors of p70(S6) kinase, p42/44 mitogen-activated protein kinase (MAPK), p38 MAPK, and phosphatidylinositol 3-kinase (PI3K). |
| 2150 | 12502492 | Human preadipocytes were induced to differentiate in insulin, dexamethasone, triiodothyronine, and 3-isobutyl-1-methylxanthine in the presence or absence of inhibitors and the peroxisome proliferator-activated receptor (PPAR)-gamma activator rosiglitazone. |
| 2151 | 12502492 | None of the inhibitors significantly inhibited protein content over 20 days, but lipid content and lipogenic activity were inhibited by p70(S6) kinase and p38 MAPK inhibition but not by p42/44 MAPK or PI3K inhibition. |
| 2152 | 12502492 | We conclude that PI3K and p42/44 MAPK pathways are not critical to the differentiation program leading to lipid accumulation, but stimulation of leptin secretion is dependent on these as well as the p70(S6) kinase and p38 MAPK signaling pathways. |
| 2153 | 12502492 | Differential regulation of lipogenesis and leptin production by independent signaling pathways and rosiglitazone during human adipocyte differentiation. |
| 2154 | 12502492 | We used inhibitors of p70(S6) kinase, p42/44 mitogen-activated protein kinase (MAPK), p38 MAPK, and phosphatidylinositol 3-kinase (PI3K). |
| 2155 | 12502492 | Human preadipocytes were induced to differentiate in insulin, dexamethasone, triiodothyronine, and 3-isobutyl-1-methylxanthine in the presence or absence of inhibitors and the peroxisome proliferator-activated receptor (PPAR)-gamma activator rosiglitazone. |
| 2156 | 12502492 | None of the inhibitors significantly inhibited protein content over 20 days, but lipid content and lipogenic activity were inhibited by p70(S6) kinase and p38 MAPK inhibition but not by p42/44 MAPK or PI3K inhibition. |
| 2157 | 12502492 | We conclude that PI3K and p42/44 MAPK pathways are not critical to the differentiation program leading to lipid accumulation, but stimulation of leptin secretion is dependent on these as well as the p70(S6) kinase and p38 MAPK signaling pathways. |
| 2158 | 12502677 | Promoter polymorphisms -359T/C and -303A/G of the catalytic subunit p110beta gene of human phosphatidylinositol 3-kinase are not associated with insulin secretion or insulin sensitivity in finnish subjects. |
| 2159 | 12502902 | In vivo administration of glucosamine inhibited phosphatidylinositol 3-kinase activity without affecting tyrosine phosphorylation of the insulin receptor or insulin receptor substrate in rat adipocytes. |
| 2160 | 12502902 | Glucosamine had no effect on the insulin-stimulated tyrosine phosphorylation of the insulin receptor and insulin receptor substrate (IRS)-1. |
| 2161 | 12502902 | Glucosamine infusion also inhibited insulin-stimulated PI 3-kinase activity associated with IRS-1, 2, 3 by 30%, 43%, and 44%, respectively. |
| 2162 | 12502902 | There was no difference in the association of the 85kDa subunit of PI 3-kinase with the IRS-1 and IRS-2 protein. |
| 2163 | 12502902 | When we measured the kinase activity of protein kinase C (PKC) lamda, which is the downstream effector of PI 3-kinase in isolated adipocytes, we found that glucosamine inhibited insulin stimulated PKClamda kinase activity by 33%. |
| 2164 | 12510059 | Modulation of insulin-stimulated degradation of human insulin receptor substrate-1 by Serine 312 phosphorylation. |
| 2165 | 12510059 | One potential mechanism for this is that Ser/Thr phosphorylation decreases the ability of IRS-1 to be tyrosine-phosphorylated by the insulin receptor. |
| 2166 | 12510059 | An additional mechanism for modulating insulin signaling is via the down-regulation of IRS-1 protein levels. |
| 2167 | 12510059 | Insulin-induced degradation of IRS-1 has been well documented, both in cells as well as in patients with diabetes. |
| 2168 | 12510059 | In the present study we have examined the potential role of different signaling cascades in the insulin-induced degradation of IRS-1. |
| 2169 | 12510059 | Second, knockout cells lacking one of the key effectors of this cascade, the phosphoinositide-dependent kinase-1, were found to be deficient in the insulin-stimulated degradation of IRS-1. |
| 2170 | 12510059 | Conversely, overexpression of this enzyme potentiated insulin-stimulated IRS-1 degradation. |
| 2171 | 12510059 | Third, concurrent with the decrease in IRS-1 degradation, the inhibitors of the phosphatidylinositol 3-kinase and mammalian target of rapamycin also blocked the insulin-stimulated increase in Ser(312) phosphorylation. |
| 2172 | 12510059 | Most important, an IRS-1 mutant in which Ser(312) was changed to alanine was found to be resistant to insulin-stimulated IRS-1 degradation. |
| 2173 | 12510059 | Finally, an inhibitor of c-Jun N-terminal kinase, SP600125, at 10 microm did not block IRS-1 degradation and IRS-1 Ser(312) phosphorylation yet completely blocked insulin-stimulated c-Jun phosphorylation. |
| 2174 | 12510059 | Further, insulin-stimulated c-Jun phosphorylation was not blocked by inhibitors of the phosphatidylinositol 3-kinase and mammalian target of rapamycin, indicating that c-Jun N-terminal kinase is unlikely to be the kinase phosphorylating IRS-1 Ser(312) in response to insulin. |
| 2175 | 12510059 | In summary, our results indicate that the insulin-stimulated degradation of IRS-1 via the phosphatidylinositol 3-kinase pathway is in part dependent upon the Ser(312) phosphorylation of IRS-1. |
| 2176 | 12510059 | Modulation of insulin-stimulated degradation of human insulin receptor substrate-1 by Serine 312 phosphorylation. |
| 2177 | 12510059 | One potential mechanism for this is that Ser/Thr phosphorylation decreases the ability of IRS-1 to be tyrosine-phosphorylated by the insulin receptor. |
| 2178 | 12510059 | An additional mechanism for modulating insulin signaling is via the down-regulation of IRS-1 protein levels. |
| 2179 | 12510059 | Insulin-induced degradation of IRS-1 has been well documented, both in cells as well as in patients with diabetes. |
| 2180 | 12510059 | In the present study we have examined the potential role of different signaling cascades in the insulin-induced degradation of IRS-1. |
| 2181 | 12510059 | Second, knockout cells lacking one of the key effectors of this cascade, the phosphoinositide-dependent kinase-1, were found to be deficient in the insulin-stimulated degradation of IRS-1. |
| 2182 | 12510059 | Conversely, overexpression of this enzyme potentiated insulin-stimulated IRS-1 degradation. |
| 2183 | 12510059 | Third, concurrent with the decrease in IRS-1 degradation, the inhibitors of the phosphatidylinositol 3-kinase and mammalian target of rapamycin also blocked the insulin-stimulated increase in Ser(312) phosphorylation. |
| 2184 | 12510059 | Most important, an IRS-1 mutant in which Ser(312) was changed to alanine was found to be resistant to insulin-stimulated IRS-1 degradation. |
| 2185 | 12510059 | Finally, an inhibitor of c-Jun N-terminal kinase, SP600125, at 10 microm did not block IRS-1 degradation and IRS-1 Ser(312) phosphorylation yet completely blocked insulin-stimulated c-Jun phosphorylation. |
| 2186 | 12510059 | Further, insulin-stimulated c-Jun phosphorylation was not blocked by inhibitors of the phosphatidylinositol 3-kinase and mammalian target of rapamycin, indicating that c-Jun N-terminal kinase is unlikely to be the kinase phosphorylating IRS-1 Ser(312) in response to insulin. |
| 2187 | 12510059 | In summary, our results indicate that the insulin-stimulated degradation of IRS-1 via the phosphatidylinositol 3-kinase pathway is in part dependent upon the Ser(312) phosphorylation of IRS-1. |
| 2188 | 12510059 | Modulation of insulin-stimulated degradation of human insulin receptor substrate-1 by Serine 312 phosphorylation. |
| 2189 | 12510059 | One potential mechanism for this is that Ser/Thr phosphorylation decreases the ability of IRS-1 to be tyrosine-phosphorylated by the insulin receptor. |
| 2190 | 12510059 | An additional mechanism for modulating insulin signaling is via the down-regulation of IRS-1 protein levels. |
| 2191 | 12510059 | Insulin-induced degradation of IRS-1 has been well documented, both in cells as well as in patients with diabetes. |
| 2192 | 12510059 | In the present study we have examined the potential role of different signaling cascades in the insulin-induced degradation of IRS-1. |
| 2193 | 12510059 | Second, knockout cells lacking one of the key effectors of this cascade, the phosphoinositide-dependent kinase-1, were found to be deficient in the insulin-stimulated degradation of IRS-1. |
| 2194 | 12510059 | Conversely, overexpression of this enzyme potentiated insulin-stimulated IRS-1 degradation. |
| 2195 | 12510059 | Third, concurrent with the decrease in IRS-1 degradation, the inhibitors of the phosphatidylinositol 3-kinase and mammalian target of rapamycin also blocked the insulin-stimulated increase in Ser(312) phosphorylation. |
| 2196 | 12510059 | Most important, an IRS-1 mutant in which Ser(312) was changed to alanine was found to be resistant to insulin-stimulated IRS-1 degradation. |
| 2197 | 12510059 | Finally, an inhibitor of c-Jun N-terminal kinase, SP600125, at 10 microm did not block IRS-1 degradation and IRS-1 Ser(312) phosphorylation yet completely blocked insulin-stimulated c-Jun phosphorylation. |
| 2198 | 12510059 | Further, insulin-stimulated c-Jun phosphorylation was not blocked by inhibitors of the phosphatidylinositol 3-kinase and mammalian target of rapamycin, indicating that c-Jun N-terminal kinase is unlikely to be the kinase phosphorylating IRS-1 Ser(312) in response to insulin. |
| 2199 | 12510059 | In summary, our results indicate that the insulin-stimulated degradation of IRS-1 via the phosphatidylinositol 3-kinase pathway is in part dependent upon the Ser(312) phosphorylation of IRS-1. |
| 2200 | 12519871 | No defects in IRS-2 expression, insulin-stimulated phosphorylation, or binding to the p85 subunit of phosphatidylinositol 3-kinase were observed. |
| 2201 | 12522122 | The effects of D-glucose were mimicked by levcromakalim (ATP-sensitive K+ channel blocker), paralleled by p42/p44(mapk) and Ser(1177)-endothelial NO synthase phosphorylation, inhibited by N(G)-nitro-L-arginine methyl ester (L-NAME; NO synthesis inhibitor), glibenclamide (ATP-sensitive K+ channel blocker), KT-5823 (protein kinase G inhibitor), PD-98059 (mitogen-activated protein kinase kinase 1/2 inhibitor), and wortmannin (phosphatidylinositol 3-kinase inhibitor), but they were unaffected by calphostin C (protein kinase C inhibitor). |
| 2202 | 12534368 | Insulin can block apoptosis by decreasing oxidative stress via phosphatidylinositol 3-kinase- and extracellular signal-regulated protein kinase-dependent signaling pathways in HepG2 cells. |
| 2203 | 12540590 | Insulin activation of phosphatidylinositol 3-kinase in the hypothalamic arcuate nucleus: a key mediator of insulin-induced anorexia. |
| 2204 | 12540590 | In peripheral tissues, insulin signaling involves activation of the insulin receptor substrate (IRS)-phosphatidylinositol 3-kinase (PI3K) enzyme system. |
| 2205 | 12540590 | In the hypothalamus, insulin functions with leptin as an afferent adiposity signal important for the regulation of body fat stores and hepatic glucose metabolism. |
| 2206 | 12540590 | To test the hypothesis that hypothalamic insulin action involves intracellular PI3K signaling, we used histochemical and biochemical methods to determine the effect of insulin on hypothalamic IRS-PI3K activity. |
| 2207 | 12540590 | Here, we report that insulin induces tyrosine phosphorylation of the insulin receptor and IRS-1 and -2, increases binding of activated IRS-1 and -2 to the regulatory subunit of PI3K, and activates protein kinase B/Akt, a downstream target of PI3K. |
| 2208 | 12540590 | Using an immunohistochemical technique to detect PI 3,4,5-triphosphate, the main product of PI3K activity, we further demonstrate that in the arcuate nucleus, insulin-induced PI3K activity occurs preferentially within cells that contain IRS-2. |
| 2209 | 12540590 | Finally, we show that the food intake- lowering effects of insulin are reversed by intracerebroventricular infusion of either of two PI3K inhibitors at doses that have no independent feeding effects. |
| 2210 | 12540590 | These findings support the hypothesis that the IRS-PI3K pathway is a mediator of insulin action in the arcuate nucleus and, combined with recent evidence that leptin activates PI3K signaling in the hypothalamus, provide a plausible mechanism for neuronal cross-talk between insulin and leptin signaling. |
| 2211 | 12540590 | Insulin activation of phosphatidylinositol 3-kinase in the hypothalamic arcuate nucleus: a key mediator of insulin-induced anorexia. |
| 2212 | 12540590 | In peripheral tissues, insulin signaling involves activation of the insulin receptor substrate (IRS)-phosphatidylinositol 3-kinase (PI3K) enzyme system. |
| 2213 | 12540590 | In the hypothalamus, insulin functions with leptin as an afferent adiposity signal important for the regulation of body fat stores and hepatic glucose metabolism. |
| 2214 | 12540590 | To test the hypothesis that hypothalamic insulin action involves intracellular PI3K signaling, we used histochemical and biochemical methods to determine the effect of insulin on hypothalamic IRS-PI3K activity. |
| 2215 | 12540590 | Here, we report that insulin induces tyrosine phosphorylation of the insulin receptor and IRS-1 and -2, increases binding of activated IRS-1 and -2 to the regulatory subunit of PI3K, and activates protein kinase B/Akt, a downstream target of PI3K. |
| 2216 | 12540590 | Using an immunohistochemical technique to detect PI 3,4,5-triphosphate, the main product of PI3K activity, we further demonstrate that in the arcuate nucleus, insulin-induced PI3K activity occurs preferentially within cells that contain IRS-2. |
| 2217 | 12540590 | Finally, we show that the food intake- lowering effects of insulin are reversed by intracerebroventricular infusion of either of two PI3K inhibitors at doses that have no independent feeding effects. |
| 2218 | 12540590 | These findings support the hypothesis that the IRS-PI3K pathway is a mediator of insulin action in the arcuate nucleus and, combined with recent evidence that leptin activates PI3K signaling in the hypothalamus, provide a plausible mechanism for neuronal cross-talk between insulin and leptin signaling. |
| 2219 | 12540590 | Insulin activation of phosphatidylinositol 3-kinase in the hypothalamic arcuate nucleus: a key mediator of insulin-induced anorexia. |
| 2220 | 12540590 | In peripheral tissues, insulin signaling involves activation of the insulin receptor substrate (IRS)-phosphatidylinositol 3-kinase (PI3K) enzyme system. |
| 2221 | 12540590 | In the hypothalamus, insulin functions with leptin as an afferent adiposity signal important for the regulation of body fat stores and hepatic glucose metabolism. |
| 2222 | 12540590 | To test the hypothesis that hypothalamic insulin action involves intracellular PI3K signaling, we used histochemical and biochemical methods to determine the effect of insulin on hypothalamic IRS-PI3K activity. |
| 2223 | 12540590 | Here, we report that insulin induces tyrosine phosphorylation of the insulin receptor and IRS-1 and -2, increases binding of activated IRS-1 and -2 to the regulatory subunit of PI3K, and activates protein kinase B/Akt, a downstream target of PI3K. |
| 2224 | 12540590 | Using an immunohistochemical technique to detect PI 3,4,5-triphosphate, the main product of PI3K activity, we further demonstrate that in the arcuate nucleus, insulin-induced PI3K activity occurs preferentially within cells that contain IRS-2. |
| 2225 | 12540590 | Finally, we show that the food intake- lowering effects of insulin are reversed by intracerebroventricular infusion of either of two PI3K inhibitors at doses that have no independent feeding effects. |
| 2226 | 12540590 | These findings support the hypothesis that the IRS-PI3K pathway is a mediator of insulin action in the arcuate nucleus and, combined with recent evidence that leptin activates PI3K signaling in the hypothalamus, provide a plausible mechanism for neuronal cross-talk between insulin and leptin signaling. |
| 2227 | 12540590 | Insulin activation of phosphatidylinositol 3-kinase in the hypothalamic arcuate nucleus: a key mediator of insulin-induced anorexia. |
| 2228 | 12540590 | In peripheral tissues, insulin signaling involves activation of the insulin receptor substrate (IRS)-phosphatidylinositol 3-kinase (PI3K) enzyme system. |
| 2229 | 12540590 | In the hypothalamus, insulin functions with leptin as an afferent adiposity signal important for the regulation of body fat stores and hepatic glucose metabolism. |
| 2230 | 12540590 | To test the hypothesis that hypothalamic insulin action involves intracellular PI3K signaling, we used histochemical and biochemical methods to determine the effect of insulin on hypothalamic IRS-PI3K activity. |
| 2231 | 12540590 | Here, we report that insulin induces tyrosine phosphorylation of the insulin receptor and IRS-1 and -2, increases binding of activated IRS-1 and -2 to the regulatory subunit of PI3K, and activates protein kinase B/Akt, a downstream target of PI3K. |
| 2232 | 12540590 | Using an immunohistochemical technique to detect PI 3,4,5-triphosphate, the main product of PI3K activity, we further demonstrate that in the arcuate nucleus, insulin-induced PI3K activity occurs preferentially within cells that contain IRS-2. |
| 2233 | 12540590 | Finally, we show that the food intake- lowering effects of insulin are reversed by intracerebroventricular infusion of either of two PI3K inhibitors at doses that have no independent feeding effects. |
| 2234 | 12540590 | These findings support the hypothesis that the IRS-PI3K pathway is a mediator of insulin action in the arcuate nucleus and, combined with recent evidence that leptin activates PI3K signaling in the hypothalamus, provide a plausible mechanism for neuronal cross-talk between insulin and leptin signaling. |
| 2235 | 12540590 | Insulin activation of phosphatidylinositol 3-kinase in the hypothalamic arcuate nucleus: a key mediator of insulin-induced anorexia. |
| 2236 | 12540590 | In peripheral tissues, insulin signaling involves activation of the insulin receptor substrate (IRS)-phosphatidylinositol 3-kinase (PI3K) enzyme system. |
| 2237 | 12540590 | In the hypothalamus, insulin functions with leptin as an afferent adiposity signal important for the regulation of body fat stores and hepatic glucose metabolism. |
| 2238 | 12540590 | To test the hypothesis that hypothalamic insulin action involves intracellular PI3K signaling, we used histochemical and biochemical methods to determine the effect of insulin on hypothalamic IRS-PI3K activity. |
| 2239 | 12540590 | Here, we report that insulin induces tyrosine phosphorylation of the insulin receptor and IRS-1 and -2, increases binding of activated IRS-1 and -2 to the regulatory subunit of PI3K, and activates protein kinase B/Akt, a downstream target of PI3K. |
| 2240 | 12540590 | Using an immunohistochemical technique to detect PI 3,4,5-triphosphate, the main product of PI3K activity, we further demonstrate that in the arcuate nucleus, insulin-induced PI3K activity occurs preferentially within cells that contain IRS-2. |
| 2241 | 12540590 | Finally, we show that the food intake- lowering effects of insulin are reversed by intracerebroventricular infusion of either of two PI3K inhibitors at doses that have no independent feeding effects. |
| 2242 | 12540590 | These findings support the hypothesis that the IRS-PI3K pathway is a mediator of insulin action in the arcuate nucleus and, combined with recent evidence that leptin activates PI3K signaling in the hypothalamus, provide a plausible mechanism for neuronal cross-talk between insulin and leptin signaling. |
| 2243 | 12540590 | Insulin activation of phosphatidylinositol 3-kinase in the hypothalamic arcuate nucleus: a key mediator of insulin-induced anorexia. |
| 2244 | 12540590 | In peripheral tissues, insulin signaling involves activation of the insulin receptor substrate (IRS)-phosphatidylinositol 3-kinase (PI3K) enzyme system. |
| 2245 | 12540590 | In the hypothalamus, insulin functions with leptin as an afferent adiposity signal important for the regulation of body fat stores and hepatic glucose metabolism. |
| 2246 | 12540590 | To test the hypothesis that hypothalamic insulin action involves intracellular PI3K signaling, we used histochemical and biochemical methods to determine the effect of insulin on hypothalamic IRS-PI3K activity. |
| 2247 | 12540590 | Here, we report that insulin induces tyrosine phosphorylation of the insulin receptor and IRS-1 and -2, increases binding of activated IRS-1 and -2 to the regulatory subunit of PI3K, and activates protein kinase B/Akt, a downstream target of PI3K. |
| 2248 | 12540590 | Using an immunohistochemical technique to detect PI 3,4,5-triphosphate, the main product of PI3K activity, we further demonstrate that in the arcuate nucleus, insulin-induced PI3K activity occurs preferentially within cells that contain IRS-2. |
| 2249 | 12540590 | Finally, we show that the food intake- lowering effects of insulin are reversed by intracerebroventricular infusion of either of two PI3K inhibitors at doses that have no independent feeding effects. |
| 2250 | 12540590 | These findings support the hypothesis that the IRS-PI3K pathway is a mediator of insulin action in the arcuate nucleus and, combined with recent evidence that leptin activates PI3K signaling in the hypothalamus, provide a plausible mechanism for neuronal cross-talk between insulin and leptin signaling. |
| 2251 | 12540590 | Insulin activation of phosphatidylinositol 3-kinase in the hypothalamic arcuate nucleus: a key mediator of insulin-induced anorexia. |
| 2252 | 12540590 | In peripheral tissues, insulin signaling involves activation of the insulin receptor substrate (IRS)-phosphatidylinositol 3-kinase (PI3K) enzyme system. |
| 2253 | 12540590 | In the hypothalamus, insulin functions with leptin as an afferent adiposity signal important for the regulation of body fat stores and hepatic glucose metabolism. |
| 2254 | 12540590 | To test the hypothesis that hypothalamic insulin action involves intracellular PI3K signaling, we used histochemical and biochemical methods to determine the effect of insulin on hypothalamic IRS-PI3K activity. |
| 2255 | 12540590 | Here, we report that insulin induces tyrosine phosphorylation of the insulin receptor and IRS-1 and -2, increases binding of activated IRS-1 and -2 to the regulatory subunit of PI3K, and activates protein kinase B/Akt, a downstream target of PI3K. |
| 2256 | 12540590 | Using an immunohistochemical technique to detect PI 3,4,5-triphosphate, the main product of PI3K activity, we further demonstrate that in the arcuate nucleus, insulin-induced PI3K activity occurs preferentially within cells that contain IRS-2. |
| 2257 | 12540590 | Finally, we show that the food intake- lowering effects of insulin are reversed by intracerebroventricular infusion of either of two PI3K inhibitors at doses that have no independent feeding effects. |
| 2258 | 12540590 | These findings support the hypothesis that the IRS-PI3K pathway is a mediator of insulin action in the arcuate nucleus and, combined with recent evidence that leptin activates PI3K signaling in the hypothalamus, provide a plausible mechanism for neuronal cross-talk between insulin and leptin signaling. |
| 2259 | 12540630 | Glucose-induced phosphatidylinositol 3-kinase and mitogen-activated protein kinase-dependent upregulation of the platelet-derived growth factor-beta receptor potentiates vascular smooth muscle cell chemotaxis. |
| 2260 | 12540630 | The aim of this study was to investigate the effects of elevated D-glucose concentrations on vascular smooth muscle cell (VSMC) expression of the platelet-derived growth factor (PDGF)beta receptor and VSMC migratory behavior. |
| 2261 | 12540630 | Immunoprecipitation, immunofluorescent staining, and RT-PCR of human VSMCs showed that elevated D-glucose induced an increase in the PDGFbeta receptor that was inhibited by phosphatidylinositol 3-kinase (PI3K) and mitogen-activated protein kinase (MAPK) pathway inhibitors. |
| 2262 | 12540630 | Exposure to 25 mmol/l D-glucose (HG) induced increased phosphorylation of protein kinase B (PKB) and extracellular-regulated kinase (ERK). |
| 2263 | 12540630 | An anti-PDGFbeta receptor antibody inhibited glucose-potentiated VSMC chemotaxis, as did the inhibitors for the PI3K and MAPK pathways. |
| 2264 | 12540630 | Glucose-induced phosphatidylinositol 3-kinase and mitogen-activated protein kinase-dependent upregulation of the platelet-derived growth factor-beta receptor potentiates vascular smooth muscle cell chemotaxis. |
| 2265 | 12540630 | The aim of this study was to investigate the effects of elevated D-glucose concentrations on vascular smooth muscle cell (VSMC) expression of the platelet-derived growth factor (PDGF)beta receptor and VSMC migratory behavior. |
| 2266 | 12540630 | Immunoprecipitation, immunofluorescent staining, and RT-PCR of human VSMCs showed that elevated D-glucose induced an increase in the PDGFbeta receptor that was inhibited by phosphatidylinositol 3-kinase (PI3K) and mitogen-activated protein kinase (MAPK) pathway inhibitors. |
| 2267 | 12540630 | Exposure to 25 mmol/l D-glucose (HG) induced increased phosphorylation of protein kinase B (PKB) and extracellular-regulated kinase (ERK). |
| 2268 | 12540630 | An anti-PDGFbeta receptor antibody inhibited glucose-potentiated VSMC chemotaxis, as did the inhibitors for the PI3K and MAPK pathways. |
| 2269 | 12540630 | Glucose-induced phosphatidylinositol 3-kinase and mitogen-activated protein kinase-dependent upregulation of the platelet-derived growth factor-beta receptor potentiates vascular smooth muscle cell chemotaxis. |
| 2270 | 12540630 | The aim of this study was to investigate the effects of elevated D-glucose concentrations on vascular smooth muscle cell (VSMC) expression of the platelet-derived growth factor (PDGF)beta receptor and VSMC migratory behavior. |
| 2271 | 12540630 | Immunoprecipitation, immunofluorescent staining, and RT-PCR of human VSMCs showed that elevated D-glucose induced an increase in the PDGFbeta receptor that was inhibited by phosphatidylinositol 3-kinase (PI3K) and mitogen-activated protein kinase (MAPK) pathway inhibitors. |
| 2272 | 12540630 | Exposure to 25 mmol/l D-glucose (HG) induced increased phosphorylation of protein kinase B (PKB) and extracellular-regulated kinase (ERK). |
| 2273 | 12540630 | An anti-PDGFbeta receptor antibody inhibited glucose-potentiated VSMC chemotaxis, as did the inhibitors for the PI3K and MAPK pathways. |
| 2274 | 12554784 | TNFalpha, which activates three different MAPKs [ERK, p38, and jun amino terminal kinase (JNK)], also induces insulin resistance. |
| 2275 | 12554784 | To better understand the respective roles of these three MAPK pathways in insulin signaling and their contribution to insulin resistance, constitutively active MAPK/ERK kinase (MEK)1, MAPK kinase (MKK6), and MKK7 mutants were overexpressed in 3T3-L1 adipocytes using an adenovirus-mediated transfection procedure. |
| 2276 | 12554784 | The MEK1 mutant, which activates ERK, markedly down-regulated expression of the insulin receptor (IR) and its major substrates, IRS-1 and IRS-2, mRNA and protein, and in turn reduced tyrosine phosphorylation of IR as well as IRS-1 and IRS-2 and their associated phosphatidyl inositol 3-kinase (PI3K) activity. |
| 2277 | 12554784 | The MKK6 mutant, which activates p38, moderately inhibited IRS-1 and IRS-2 expressions and IRS-1-associated PI3K activity without exerting a significant effect on the IR. |
| 2278 | 12554784 | Finally, the MKK7 mutant, which activates JNK, reduced tyrosine phosphorylation of IRS-1 and IRS-2 and IRS-associated PI3K activity without affecting expression of the IR, IRS-1, or IRS-2. |
| 2279 | 12554784 | In the context of our earlier report showing down-regulation of glucose transporter 4 by MEK1-ERK and MKK6/3-p38, the present findings suggest that chronic activation of ERK, p38, or JNK can induce insulin resistance by affecting glucose transporter expression and insulin signaling, though via distinctly different mechanisms. |
| 2280 | 12554784 | TNFalpha, which activates three different MAPKs [ERK, p38, and jun amino terminal kinase (JNK)], also induces insulin resistance. |
| 2281 | 12554784 | To better understand the respective roles of these three MAPK pathways in insulin signaling and their contribution to insulin resistance, constitutively active MAPK/ERK kinase (MEK)1, MAPK kinase (MKK6), and MKK7 mutants were overexpressed in 3T3-L1 adipocytes using an adenovirus-mediated transfection procedure. |
| 2282 | 12554784 | The MEK1 mutant, which activates ERK, markedly down-regulated expression of the insulin receptor (IR) and its major substrates, IRS-1 and IRS-2, mRNA and protein, and in turn reduced tyrosine phosphorylation of IR as well as IRS-1 and IRS-2 and their associated phosphatidyl inositol 3-kinase (PI3K) activity. |
| 2283 | 12554784 | The MKK6 mutant, which activates p38, moderately inhibited IRS-1 and IRS-2 expressions and IRS-1-associated PI3K activity without exerting a significant effect on the IR. |
| 2284 | 12554784 | Finally, the MKK7 mutant, which activates JNK, reduced tyrosine phosphorylation of IRS-1 and IRS-2 and IRS-associated PI3K activity without affecting expression of the IR, IRS-1, or IRS-2. |
| 2285 | 12554784 | In the context of our earlier report showing down-regulation of glucose transporter 4 by MEK1-ERK and MKK6/3-p38, the present findings suggest that chronic activation of ERK, p38, or JNK can induce insulin resistance by affecting glucose transporter expression and insulin signaling, though via distinctly different mechanisms. |
| 2286 | 12554784 | TNFalpha, which activates three different MAPKs [ERK, p38, and jun amino terminal kinase (JNK)], also induces insulin resistance. |
| 2287 | 12554784 | To better understand the respective roles of these three MAPK pathways in insulin signaling and their contribution to insulin resistance, constitutively active MAPK/ERK kinase (MEK)1, MAPK kinase (MKK6), and MKK7 mutants were overexpressed in 3T3-L1 adipocytes using an adenovirus-mediated transfection procedure. |
| 2288 | 12554784 | The MEK1 mutant, which activates ERK, markedly down-regulated expression of the insulin receptor (IR) and its major substrates, IRS-1 and IRS-2, mRNA and protein, and in turn reduced tyrosine phosphorylation of IR as well as IRS-1 and IRS-2 and their associated phosphatidyl inositol 3-kinase (PI3K) activity. |
| 2289 | 12554784 | The MKK6 mutant, which activates p38, moderately inhibited IRS-1 and IRS-2 expressions and IRS-1-associated PI3K activity without exerting a significant effect on the IR. |
| 2290 | 12554784 | Finally, the MKK7 mutant, which activates JNK, reduced tyrosine phosphorylation of IRS-1 and IRS-2 and IRS-associated PI3K activity without affecting expression of the IR, IRS-1, or IRS-2. |
| 2291 | 12554784 | In the context of our earlier report showing down-regulation of glucose transporter 4 by MEK1-ERK and MKK6/3-p38, the present findings suggest that chronic activation of ERK, p38, or JNK can induce insulin resistance by affecting glucose transporter expression and insulin signaling, though via distinctly different mechanisms. |
| 2292 | 12560330 | Suppressor of cytokine signaling-3 (SOCS-3), a potential mediator of interleukin-6-dependent insulin resistance in hepatocytes. |
| 2293 | 12560330 | Interleukin-6 (IL-6) is one of several pro-inflammatory cytokines implicated in insulin resistance during infection, cachexia, and obesity. |
| 2294 | 12560330 | We recently demonstrated that IL-6 inhibits insulin signaling in hepatocytes (Senn, J. |
| 2295 | 12560330 | Members of the suppressors of cytokine signaling (SOCS) family associate with the insulin receptor (IR), and their ectopic expression inhibits IR signaling. |
| 2296 | 12560330 | Since several SOCS proteins are induced by IL-6, a working hypothesis is that IL-6-dependent insulin resistance is mediated, at least in part, by induction of SOCS protein(s) in insulin target cells. |
| 2297 | 12560330 | To examine the involvement of SOCS protein(s) in IL-6-dependent inhibition of insulin receptor signaling, HepG2 cells were treated with IL-6 (20 ng/ml) for periods from 1 min to 8 h. |
| 2298 | 12560330 | IL-6 induced SOCS-3 transcript at 30 min with a maximum effect at 1 h. |
| 2299 | 12560330 | SOCS-3 induction by IL-6 paralleled IL-6-dependent inhibition of IR signal transduction. |
| 2300 | 12560330 | Ectopically expressed SOCS-3 associated with the IR and suppressed insulin-dependent receptor autophosphorylation, insulin receptor substrate-1 (IRS-1) tyrosine phosphorylation, association of IRS-1 with the p85 subunit of phosphatidylinositol 3-kinase, and activation of Akt. |
| 2301 | 12560330 | SOCS-3 was also a direct inhibitor of insulin receptor autophosphorylation in vitro. |
| 2302 | 12560330 | In mice exposed to IL-6 for 60-90 min, hepatic SOCS-3 expression was increased. |
| 2303 | 12560330 | This was associated with inhibition of hepatic insulin-dependent receptor autophosphorylation and IRS-1 tyrosine phosphorylation. |
| 2304 | 12560330 | These data suggest that induction of SOCS-3 in liver may be an important mechanism of IL-6-mediated insulin resistance. |
| 2305 | 12586357 | Essential role of protein kinase C zeta in the impairment of insulin-induced glucose transport in IRS-2-deficient brown adipocytes. |
| 2306 | 12586357 | We have investigated the molecular mechanisms by which IRS-2(-/-) immortalized brown adipocytes showed an impaired response to insulin in inducing GLUT4 translocation and glucose uptake. |
| 2307 | 12586357 | IRS-2-associated phosphatidylinositol 3-kinase (PI 3-kinase) activity was blunted in IRS-2(-/-) cells, total PI 3-kinase activity being reduced by 30%. |
| 2308 | 12586357 | Downstream, activation of protein kinase C (PKC) zeta was abolished in IRS-2(-/-) cells. |
| 2309 | 12586357 | Reconstitution with retroviral IRS-2 restores IRS-2/PI 3-kinase/PKC zeta signalling, as well as glucose uptake. |
| 2310 | 12586357 | Wild-type cells expressing a kinase-inactive mutant of PKC zeta lack GLUT4 translocation and glucose uptake. |
| 2311 | 12586357 | Our results support the essential role played by PKC zeta in the insulin resistance and impaired glucose uptake observed in IRS-2-deficient brown adipocytes. |
| 2312 | 12591159 | Abnormal PI3 kinase/Akt signal pathway in vagal afferent neurons and vagus nerve of streptozotocin-diabetic rats. |
| 2313 | 12591159 | The PI3 (phosphatidylinositol-3) kinase/Akt (protein kinase B) signal pathway is involved in the molecular signaling that regulates retrograde axonal transport of neurotrophins in the nervous system. |
| 2314 | 12591159 | Previous work showed that a reduced retrograde axonal transport of endogenous nerve growth factor (NGF) and neurotrophin-3 (NT-3) in the vagus nerve of diabetic rats occurred in the presence of normal production of neurotrophins and neurotrophin receptors. |
| 2315 | 12591159 | To assess the potential involvement of an impaired PI3 kinase/Akt signal pathway in the diabetes-induced reduction in retrograde axonal transport of neurotrophins in the vagus nerve, we characterized diabetes-induced changes in the PI3 kinase/Akt signal pathway in the vagus nerve and vagal afferent neurons. |
| 2316 | 12591159 | Control and streptozotocin (STZ)-induced diabetic rats with a duration of 16 weeks, kinase assays, Western blotting, and immunocytochemistry were used to show that diabetes resulted in alterations in activity and protein expression of the PI3 kinase/Akt signal pathway in the vagus nerve and vagal afferent neurons. |
| 2317 | 12591159 | Diabetes caused a significant decrease in enzymatic activity of PI3 kinase and Akt (52 and 36% of control, respectively) in the vagus nerve. |
| 2318 | 12591159 | The reduced enzymatic activity was not associated with decreased protein expression of the p85 subunit of PI3 kinase, Akt and phosphorylation of Akt (ser473). |
| 2319 | 12591159 | However, diabetes induced an overall decrease in immunoreactivity of the p85 subunit of PI3 kinase, phospho-Akt (ser473) and phospho-p70s6/p85s6 kinase (thr421/ser424) in vagal afferent neurons. |
| 2320 | 12591159 | Thus, impaired PI3 kinase/Akt signal pathway may partly account for the reduced retrograde axonal transport of neurotrophins in the vagus nerve of STZ-induced diabetic rats. |
| 2321 | 12594228 | Phosphoinositide 3-kinase-mediated reduction of insulin receptor substrate-1/2 protein expression via different mechanisms contributes to the insulin-induced desensitization of its signaling pathways in L6 muscle cells. |
| 2322 | 12594228 | A 24-h long insulin treatment desensitized the phosphoinositide 3-kinase (PI3K)/protein kinase B (PKB) and p42/p44 MAPK pathways toward a second stimulation with insulin or insulin-like growth factor-1 and led to decreased insulin-induced glucose uptake. |
| 2323 | 12594228 | Desensitization was correlated to a reduction in insulin receptor substrate (IRS)-1 and IRS-2 protein levels, which was reversed by the PI3K inhibitor LY294002. |
| 2324 | 12594228 | Co-treatment of cells with insulin and LY294002, while reducing total IRS-1 phosphorylation, increased its phosphotyrosine content, enhancing IRS-1/PI3K association. |
| 2325 | 12594228 | PDK1, mTOR, and MAPK inhibitors did not block insulin-induced reduction of IRS-1, suggesting that the PI3K serine-kinase activity causes IRS-1 serine phosphorylation and its commitment to proteasomal degradation. |
| 2326 | 12594228 | Contrarily, insulin-induced IRS-2 down-regulation occurred via a PI3K/mTOR pathway. |
| 2327 | 12594228 | Suppression of IRS-1/2 down-regulation by LY294002 rescued the responsiveness of PKB and MAPK toward acute insulin stimulation. |
| 2328 | 12594228 | Conversely, adenoviral-driven expression of constitutively active PI3K induced an insulin-independent reduction in IRS-1/2 protein levels. |
| 2329 | 12594228 | IRS-2 appears to be the chief molecule responsible for MAPK and PKB activation by insulin, as knockdown of IRS-2 (but not IRS-1) by RNA interference severely impaired activation of both kinases. |
| 2330 | 12594228 | In summary, (i) PI3K mediates insulin-induced reduction of IRS-1 by phosphorylating it while a PI3K/mTOR pathway controls insulin-induced reduction of IRS-2, (ii) in L6 cells, IRS-2 is the major adapter molecule linking the insulin receptor to activation of PKB and MAPK, (iii) the mechanism of IRS-1/2 down-regulation is different in L6 cells compared with 3T3-L1 adipocytes. |
| 2331 | 12594228 | In conclusion, the reduction in IRS proteins via different PI3K-mediated mechanisms contributes to the development of an insulin-resistant state in L6 myoblasts. |
| 2332 | 12594228 | Phosphoinositide 3-kinase-mediated reduction of insulin receptor substrate-1/2 protein expression via different mechanisms contributes to the insulin-induced desensitization of its signaling pathways in L6 muscle cells. |
| 2333 | 12594228 | A 24-h long insulin treatment desensitized the phosphoinositide 3-kinase (PI3K)/protein kinase B (PKB) and p42/p44 MAPK pathways toward a second stimulation with insulin or insulin-like growth factor-1 and led to decreased insulin-induced glucose uptake. |
| 2334 | 12594228 | Desensitization was correlated to a reduction in insulin receptor substrate (IRS)-1 and IRS-2 protein levels, which was reversed by the PI3K inhibitor LY294002. |
| 2335 | 12594228 | Co-treatment of cells with insulin and LY294002, while reducing total IRS-1 phosphorylation, increased its phosphotyrosine content, enhancing IRS-1/PI3K association. |
| 2336 | 12594228 | PDK1, mTOR, and MAPK inhibitors did not block insulin-induced reduction of IRS-1, suggesting that the PI3K serine-kinase activity causes IRS-1 serine phosphorylation and its commitment to proteasomal degradation. |
| 2337 | 12594228 | Contrarily, insulin-induced IRS-2 down-regulation occurred via a PI3K/mTOR pathway. |
| 2338 | 12594228 | Suppression of IRS-1/2 down-regulation by LY294002 rescued the responsiveness of PKB and MAPK toward acute insulin stimulation. |
| 2339 | 12594228 | Conversely, adenoviral-driven expression of constitutively active PI3K induced an insulin-independent reduction in IRS-1/2 protein levels. |
| 2340 | 12594228 | IRS-2 appears to be the chief molecule responsible for MAPK and PKB activation by insulin, as knockdown of IRS-2 (but not IRS-1) by RNA interference severely impaired activation of both kinases. |
| 2341 | 12594228 | In summary, (i) PI3K mediates insulin-induced reduction of IRS-1 by phosphorylating it while a PI3K/mTOR pathway controls insulin-induced reduction of IRS-2, (ii) in L6 cells, IRS-2 is the major adapter molecule linking the insulin receptor to activation of PKB and MAPK, (iii) the mechanism of IRS-1/2 down-regulation is different in L6 cells compared with 3T3-L1 adipocytes. |
| 2342 | 12594228 | In conclusion, the reduction in IRS proteins via different PI3K-mediated mechanisms contributes to the development of an insulin-resistant state in L6 myoblasts. |
| 2343 | 12594228 | Phosphoinositide 3-kinase-mediated reduction of insulin receptor substrate-1/2 protein expression via different mechanisms contributes to the insulin-induced desensitization of its signaling pathways in L6 muscle cells. |
| 2344 | 12594228 | A 24-h long insulin treatment desensitized the phosphoinositide 3-kinase (PI3K)/protein kinase B (PKB) and p42/p44 MAPK pathways toward a second stimulation with insulin or insulin-like growth factor-1 and led to decreased insulin-induced glucose uptake. |
| 2345 | 12594228 | Desensitization was correlated to a reduction in insulin receptor substrate (IRS)-1 and IRS-2 protein levels, which was reversed by the PI3K inhibitor LY294002. |
| 2346 | 12594228 | Co-treatment of cells with insulin and LY294002, while reducing total IRS-1 phosphorylation, increased its phosphotyrosine content, enhancing IRS-1/PI3K association. |
| 2347 | 12594228 | PDK1, mTOR, and MAPK inhibitors did not block insulin-induced reduction of IRS-1, suggesting that the PI3K serine-kinase activity causes IRS-1 serine phosphorylation and its commitment to proteasomal degradation. |
| 2348 | 12594228 | Contrarily, insulin-induced IRS-2 down-regulation occurred via a PI3K/mTOR pathway. |
| 2349 | 12594228 | Suppression of IRS-1/2 down-regulation by LY294002 rescued the responsiveness of PKB and MAPK toward acute insulin stimulation. |
| 2350 | 12594228 | Conversely, adenoviral-driven expression of constitutively active PI3K induced an insulin-independent reduction in IRS-1/2 protein levels. |
| 2351 | 12594228 | IRS-2 appears to be the chief molecule responsible for MAPK and PKB activation by insulin, as knockdown of IRS-2 (but not IRS-1) by RNA interference severely impaired activation of both kinases. |
| 2352 | 12594228 | In summary, (i) PI3K mediates insulin-induced reduction of IRS-1 by phosphorylating it while a PI3K/mTOR pathway controls insulin-induced reduction of IRS-2, (ii) in L6 cells, IRS-2 is the major adapter molecule linking the insulin receptor to activation of PKB and MAPK, (iii) the mechanism of IRS-1/2 down-regulation is different in L6 cells compared with 3T3-L1 adipocytes. |
| 2353 | 12594228 | In conclusion, the reduction in IRS proteins via different PI3K-mediated mechanisms contributes to the development of an insulin-resistant state in L6 myoblasts. |
| 2354 | 12594228 | Phosphoinositide 3-kinase-mediated reduction of insulin receptor substrate-1/2 protein expression via different mechanisms contributes to the insulin-induced desensitization of its signaling pathways in L6 muscle cells. |
| 2355 | 12594228 | A 24-h long insulin treatment desensitized the phosphoinositide 3-kinase (PI3K)/protein kinase B (PKB) and p42/p44 MAPK pathways toward a second stimulation with insulin or insulin-like growth factor-1 and led to decreased insulin-induced glucose uptake. |
| 2356 | 12594228 | Desensitization was correlated to a reduction in insulin receptor substrate (IRS)-1 and IRS-2 protein levels, which was reversed by the PI3K inhibitor LY294002. |
| 2357 | 12594228 | Co-treatment of cells with insulin and LY294002, while reducing total IRS-1 phosphorylation, increased its phosphotyrosine content, enhancing IRS-1/PI3K association. |
| 2358 | 12594228 | PDK1, mTOR, and MAPK inhibitors did not block insulin-induced reduction of IRS-1, suggesting that the PI3K serine-kinase activity causes IRS-1 serine phosphorylation and its commitment to proteasomal degradation. |
| 2359 | 12594228 | Contrarily, insulin-induced IRS-2 down-regulation occurred via a PI3K/mTOR pathway. |
| 2360 | 12594228 | Suppression of IRS-1/2 down-regulation by LY294002 rescued the responsiveness of PKB and MAPK toward acute insulin stimulation. |
| 2361 | 12594228 | Conversely, adenoviral-driven expression of constitutively active PI3K induced an insulin-independent reduction in IRS-1/2 protein levels. |
| 2362 | 12594228 | IRS-2 appears to be the chief molecule responsible for MAPK and PKB activation by insulin, as knockdown of IRS-2 (but not IRS-1) by RNA interference severely impaired activation of both kinases. |
| 2363 | 12594228 | In summary, (i) PI3K mediates insulin-induced reduction of IRS-1 by phosphorylating it while a PI3K/mTOR pathway controls insulin-induced reduction of IRS-2, (ii) in L6 cells, IRS-2 is the major adapter molecule linking the insulin receptor to activation of PKB and MAPK, (iii) the mechanism of IRS-1/2 down-regulation is different in L6 cells compared with 3T3-L1 adipocytes. |
| 2364 | 12594228 | In conclusion, the reduction in IRS proteins via different PI3K-mediated mechanisms contributes to the development of an insulin-resistant state in L6 myoblasts. |
| 2365 | 12594228 | Phosphoinositide 3-kinase-mediated reduction of insulin receptor substrate-1/2 protein expression via different mechanisms contributes to the insulin-induced desensitization of its signaling pathways in L6 muscle cells. |
| 2366 | 12594228 | A 24-h long insulin treatment desensitized the phosphoinositide 3-kinase (PI3K)/protein kinase B (PKB) and p42/p44 MAPK pathways toward a second stimulation with insulin or insulin-like growth factor-1 and led to decreased insulin-induced glucose uptake. |
| 2367 | 12594228 | Desensitization was correlated to a reduction in insulin receptor substrate (IRS)-1 and IRS-2 protein levels, which was reversed by the PI3K inhibitor LY294002. |
| 2368 | 12594228 | Co-treatment of cells with insulin and LY294002, while reducing total IRS-1 phosphorylation, increased its phosphotyrosine content, enhancing IRS-1/PI3K association. |
| 2369 | 12594228 | PDK1, mTOR, and MAPK inhibitors did not block insulin-induced reduction of IRS-1, suggesting that the PI3K serine-kinase activity causes IRS-1 serine phosphorylation and its commitment to proteasomal degradation. |
| 2370 | 12594228 | Contrarily, insulin-induced IRS-2 down-regulation occurred via a PI3K/mTOR pathway. |
| 2371 | 12594228 | Suppression of IRS-1/2 down-regulation by LY294002 rescued the responsiveness of PKB and MAPK toward acute insulin stimulation. |
| 2372 | 12594228 | Conversely, adenoviral-driven expression of constitutively active PI3K induced an insulin-independent reduction in IRS-1/2 protein levels. |
| 2373 | 12594228 | IRS-2 appears to be the chief molecule responsible for MAPK and PKB activation by insulin, as knockdown of IRS-2 (but not IRS-1) by RNA interference severely impaired activation of both kinases. |
| 2374 | 12594228 | In summary, (i) PI3K mediates insulin-induced reduction of IRS-1 by phosphorylating it while a PI3K/mTOR pathway controls insulin-induced reduction of IRS-2, (ii) in L6 cells, IRS-2 is the major adapter molecule linking the insulin receptor to activation of PKB and MAPK, (iii) the mechanism of IRS-1/2 down-regulation is different in L6 cells compared with 3T3-L1 adipocytes. |
| 2375 | 12594228 | In conclusion, the reduction in IRS proteins via different PI3K-mediated mechanisms contributes to the development of an insulin-resistant state in L6 myoblasts. |
| 2376 | 12594228 | Phosphoinositide 3-kinase-mediated reduction of insulin receptor substrate-1/2 protein expression via different mechanisms contributes to the insulin-induced desensitization of its signaling pathways in L6 muscle cells. |
| 2377 | 12594228 | A 24-h long insulin treatment desensitized the phosphoinositide 3-kinase (PI3K)/protein kinase B (PKB) and p42/p44 MAPK pathways toward a second stimulation with insulin or insulin-like growth factor-1 and led to decreased insulin-induced glucose uptake. |
| 2378 | 12594228 | Desensitization was correlated to a reduction in insulin receptor substrate (IRS)-1 and IRS-2 protein levels, which was reversed by the PI3K inhibitor LY294002. |
| 2379 | 12594228 | Co-treatment of cells with insulin and LY294002, while reducing total IRS-1 phosphorylation, increased its phosphotyrosine content, enhancing IRS-1/PI3K association. |
| 2380 | 12594228 | PDK1, mTOR, and MAPK inhibitors did not block insulin-induced reduction of IRS-1, suggesting that the PI3K serine-kinase activity causes IRS-1 serine phosphorylation and its commitment to proteasomal degradation. |
| 2381 | 12594228 | Contrarily, insulin-induced IRS-2 down-regulation occurred via a PI3K/mTOR pathway. |
| 2382 | 12594228 | Suppression of IRS-1/2 down-regulation by LY294002 rescued the responsiveness of PKB and MAPK toward acute insulin stimulation. |
| 2383 | 12594228 | Conversely, adenoviral-driven expression of constitutively active PI3K induced an insulin-independent reduction in IRS-1/2 protein levels. |
| 2384 | 12594228 | IRS-2 appears to be the chief molecule responsible for MAPK and PKB activation by insulin, as knockdown of IRS-2 (but not IRS-1) by RNA interference severely impaired activation of both kinases. |
| 2385 | 12594228 | In summary, (i) PI3K mediates insulin-induced reduction of IRS-1 by phosphorylating it while a PI3K/mTOR pathway controls insulin-induced reduction of IRS-2, (ii) in L6 cells, IRS-2 is the major adapter molecule linking the insulin receptor to activation of PKB and MAPK, (iii) the mechanism of IRS-1/2 down-regulation is different in L6 cells compared with 3T3-L1 adipocytes. |
| 2386 | 12594228 | In conclusion, the reduction in IRS proteins via different PI3K-mediated mechanisms contributes to the development of an insulin-resistant state in L6 myoblasts. |
| 2387 | 12594228 | Phosphoinositide 3-kinase-mediated reduction of insulin receptor substrate-1/2 protein expression via different mechanisms contributes to the insulin-induced desensitization of its signaling pathways in L6 muscle cells. |
| 2388 | 12594228 | A 24-h long insulin treatment desensitized the phosphoinositide 3-kinase (PI3K)/protein kinase B (PKB) and p42/p44 MAPK pathways toward a second stimulation with insulin or insulin-like growth factor-1 and led to decreased insulin-induced glucose uptake. |
| 2389 | 12594228 | Desensitization was correlated to a reduction in insulin receptor substrate (IRS)-1 and IRS-2 protein levels, which was reversed by the PI3K inhibitor LY294002. |
| 2390 | 12594228 | Co-treatment of cells with insulin and LY294002, while reducing total IRS-1 phosphorylation, increased its phosphotyrosine content, enhancing IRS-1/PI3K association. |
| 2391 | 12594228 | PDK1, mTOR, and MAPK inhibitors did not block insulin-induced reduction of IRS-1, suggesting that the PI3K serine-kinase activity causes IRS-1 serine phosphorylation and its commitment to proteasomal degradation. |
| 2392 | 12594228 | Contrarily, insulin-induced IRS-2 down-regulation occurred via a PI3K/mTOR pathway. |
| 2393 | 12594228 | Suppression of IRS-1/2 down-regulation by LY294002 rescued the responsiveness of PKB and MAPK toward acute insulin stimulation. |
| 2394 | 12594228 | Conversely, adenoviral-driven expression of constitutively active PI3K induced an insulin-independent reduction in IRS-1/2 protein levels. |
| 2395 | 12594228 | IRS-2 appears to be the chief molecule responsible for MAPK and PKB activation by insulin, as knockdown of IRS-2 (but not IRS-1) by RNA interference severely impaired activation of both kinases. |
| 2396 | 12594228 | In summary, (i) PI3K mediates insulin-induced reduction of IRS-1 by phosphorylating it while a PI3K/mTOR pathway controls insulin-induced reduction of IRS-2, (ii) in L6 cells, IRS-2 is the major adapter molecule linking the insulin receptor to activation of PKB and MAPK, (iii) the mechanism of IRS-1/2 down-regulation is different in L6 cells compared with 3T3-L1 adipocytes. |
| 2397 | 12594228 | In conclusion, the reduction in IRS proteins via different PI3K-mediated mechanisms contributes to the development of an insulin-resistant state in L6 myoblasts. |
| 2398 | 12594228 | Phosphoinositide 3-kinase-mediated reduction of insulin receptor substrate-1/2 protein expression via different mechanisms contributes to the insulin-induced desensitization of its signaling pathways in L6 muscle cells. |
| 2399 | 12594228 | A 24-h long insulin treatment desensitized the phosphoinositide 3-kinase (PI3K)/protein kinase B (PKB) and p42/p44 MAPK pathways toward a second stimulation with insulin or insulin-like growth factor-1 and led to decreased insulin-induced glucose uptake. |
| 2400 | 12594228 | Desensitization was correlated to a reduction in insulin receptor substrate (IRS)-1 and IRS-2 protein levels, which was reversed by the PI3K inhibitor LY294002. |
| 2401 | 12594228 | Co-treatment of cells with insulin and LY294002, while reducing total IRS-1 phosphorylation, increased its phosphotyrosine content, enhancing IRS-1/PI3K association. |
| 2402 | 12594228 | PDK1, mTOR, and MAPK inhibitors did not block insulin-induced reduction of IRS-1, suggesting that the PI3K serine-kinase activity causes IRS-1 serine phosphorylation and its commitment to proteasomal degradation. |
| 2403 | 12594228 | Contrarily, insulin-induced IRS-2 down-regulation occurred via a PI3K/mTOR pathway. |
| 2404 | 12594228 | Suppression of IRS-1/2 down-regulation by LY294002 rescued the responsiveness of PKB and MAPK toward acute insulin stimulation. |
| 2405 | 12594228 | Conversely, adenoviral-driven expression of constitutively active PI3K induced an insulin-independent reduction in IRS-1/2 protein levels. |
| 2406 | 12594228 | IRS-2 appears to be the chief molecule responsible for MAPK and PKB activation by insulin, as knockdown of IRS-2 (but not IRS-1) by RNA interference severely impaired activation of both kinases. |
| 2407 | 12594228 | In summary, (i) PI3K mediates insulin-induced reduction of IRS-1 by phosphorylating it while a PI3K/mTOR pathway controls insulin-induced reduction of IRS-2, (ii) in L6 cells, IRS-2 is the major adapter molecule linking the insulin receptor to activation of PKB and MAPK, (iii) the mechanism of IRS-1/2 down-regulation is different in L6 cells compared with 3T3-L1 adipocytes. |
| 2408 | 12594228 | In conclusion, the reduction in IRS proteins via different PI3K-mediated mechanisms contributes to the development of an insulin-resistant state in L6 myoblasts. |
| 2409 | 12604916 | Impaired insulin action on phosphatidylinositol 3-kinase activity and glucose transport in skeletal muscle of pancreatic cancer patients. |
| 2410 | 12609497 | Insulin and leptin revisited: adiposity signals with overlapping physiological and intracellular signaling capabilities. |
| 2411 | 12609497 | The adipocyte-derived hormone leptin and the pancreatic beta cell-derived hormone insulin each function as afferent signals to the hypothalamus in an endocrine feedback loop that regulates body adiposity. |
| 2412 | 12609497 | Defects in either insulin or leptin signaling in the brain result in hyperphagia, disordered glucose homeostasis, and reproductive dysfunction. |
| 2413 | 12609497 | To explain this striking physiological overlap, we hypothesize that hypothalamic insulin and leptin signaling converge upon a single intracellular signal transduction pathway, known as the insulin-receptor-substrate phosphatidylinositol 3-kinase pathway. |
| 2414 | 12609497 | Here we synthesize data from a variety of model systems in which such "cross-talk" between insulin and leptin signal transduction has either been observed or can be inferred, discuss our own data demonstrating that insulin and leptin both activate hypothalamic phosphatidylinositol 3-kinase signaling, and discuss the significance of such convergence with respect to neuronal function in normal individuals and in pathological states such as obesity. |
| 2415 | 12609497 | Identification of the key early molecular events mediating the action of both insulin and leptin in hypothalamic neurons promises new insight into the regulation of these neurons in health and disease. |
| 2416 | 12609497 | Insulin and leptin revisited: adiposity signals with overlapping physiological and intracellular signaling capabilities. |
| 2417 | 12609497 | The adipocyte-derived hormone leptin and the pancreatic beta cell-derived hormone insulin each function as afferent signals to the hypothalamus in an endocrine feedback loop that regulates body adiposity. |
| 2418 | 12609497 | Defects in either insulin or leptin signaling in the brain result in hyperphagia, disordered glucose homeostasis, and reproductive dysfunction. |
| 2419 | 12609497 | To explain this striking physiological overlap, we hypothesize that hypothalamic insulin and leptin signaling converge upon a single intracellular signal transduction pathway, known as the insulin-receptor-substrate phosphatidylinositol 3-kinase pathway. |
| 2420 | 12609497 | Here we synthesize data from a variety of model systems in which such "cross-talk" between insulin and leptin signal transduction has either been observed or can be inferred, discuss our own data demonstrating that insulin and leptin both activate hypothalamic phosphatidylinositol 3-kinase signaling, and discuss the significance of such convergence with respect to neuronal function in normal individuals and in pathological states such as obesity. |
| 2421 | 12609497 | Identification of the key early molecular events mediating the action of both insulin and leptin in hypothalamic neurons promises new insight into the regulation of these neurons in health and disease. |
| 2422 | 12644458 | High glucose inhibits insulin-stimulated nitric oxide production without reducing endothelial nitric-oxide synthase Ser1177 phosphorylation in human aortic endothelial cells. |
| 2423 | 12644458 | Recent studies have indicated that insulin activates endothelial nitric-oxide synthase (eNOS) by protein kinase B (PKB)-mediated phosphorylation at Ser1177 in endothelial cells. |
| 2424 | 12644458 | This was accompanied by reduced expression of IRS-2 and attenuated insulin-stimulated recruitment of PI3K to IRS-1 and IRS-2, yet insulin-stimulated PKB activity and phosphorylation of eNOS at Ser1177 were unaffected. |
| 2425 | 12644458 | Furthermore, high glucose down-regulated the expression of CAP and Cbl, and insulin-stimulated Cbl phosphorylation, components of an insulin signaling cascade previously characterized in adipocytes. |
| 2426 | 12644458 | These data suggest that high glucose specifically inhibits insulin-stimulated NO synthesis and down-regulates some aspects of insulin signaling, including the CAP-Cbl signaling pathway, yet this is not a result of reduced PKB-mediated eNOS phosphorylation at Ser1177. |
| 2427 | 12647305 | Involvement of MEKK1/ERK/P21Waf1/Cip1 signal transduction pathway in inhibition of IGF-I-mediated cell growth response by methylglyoxal. |
| 2428 | 12647305 | These disturbances could modify the cell response to hormones and growth factors, including insulin-like growth factor-1 (IGF-I). |
| 2429 | 12647305 | MG rendered these cells resistant to the mitogenic action of IGF-I, and this was associated with stronger and prolonged activation of ERK and over-expression of P21(Waf1/Cip1). |
| 2430 | 12647305 | The synergistic effect of MG with IGF-I in activation of ERK was completely abolished by PD98059 but not by a specific PI3K inhibitor, LY294002, or a specific PKC inhibitor, bisindolylmaleimide. |
| 2431 | 12647305 | Blocking of Raf-1 activity by expression of a dominant negative form of Raf-1 did not reduce the enhancing effect of MG on IGF-I-induced activation of ERK. |
| 2432 | 12647305 | However, transfection of a catalytically inactive form of MEKK1 resulted in inactivation of the MG-induced activation of ERK and partial inhibition of the enhanced activation of ERK and over-expression of p21(Waf1/Cip1) induced by co-stimulation of MG and IGF-I. |
| 2433 | 12647305 | These results suggested that the alteration of intracellular milieu induced by MG through a MEKK1-mediated and PI3K/PKC/Raf-1-independent pathway resulted in the modification of cell response to IGF-I for p21(Waf1/Cip1)-mediated growth arrest, which may be one of the crucial mechanisms for MG to promote the development of chronic clinical complications in diabetes. |
| 2434 | 12647305 | Involvement of MEKK1/ERK/P21Waf1/Cip1 signal transduction pathway in inhibition of IGF-I-mediated cell growth response by methylglyoxal. |
| 2435 | 12647305 | These disturbances could modify the cell response to hormones and growth factors, including insulin-like growth factor-1 (IGF-I). |
| 2436 | 12647305 | MG rendered these cells resistant to the mitogenic action of IGF-I, and this was associated with stronger and prolonged activation of ERK and over-expression of P21(Waf1/Cip1). |
| 2437 | 12647305 | The synergistic effect of MG with IGF-I in activation of ERK was completely abolished by PD98059 but not by a specific PI3K inhibitor, LY294002, or a specific PKC inhibitor, bisindolylmaleimide. |
| 2438 | 12647305 | Blocking of Raf-1 activity by expression of a dominant negative form of Raf-1 did not reduce the enhancing effect of MG on IGF-I-induced activation of ERK. |
| 2439 | 12647305 | However, transfection of a catalytically inactive form of MEKK1 resulted in inactivation of the MG-induced activation of ERK and partial inhibition of the enhanced activation of ERK and over-expression of p21(Waf1/Cip1) induced by co-stimulation of MG and IGF-I. |
| 2440 | 12647305 | These results suggested that the alteration of intracellular milieu induced by MG through a MEKK1-mediated and PI3K/PKC/Raf-1-independent pathway resulted in the modification of cell response to IGF-I for p21(Waf1/Cip1)-mediated growth arrest, which may be one of the crucial mechanisms for MG to promote the development of chronic clinical complications in diabetes. |
| 2441 | 12663464 | Defective signaling through Akt-2 and -3 but not Akt-1 in insulin-resistant human skeletal muscle: potential role in insulin resistance. |
| 2442 | 12663464 | Recent evidence has shown that activation of phosphatidyinositol-3-kinase (PI3K) and Akt, necessary for insulin stimulation of glucose transport, is impaired in insulin resistance. |
| 2443 | 12663464 | It is unknown, however, which Akt isoform shows impaired activation in insulin resistance. |
| 2444 | 12663464 | Additionally, related growth factors (epidermal or platelet-derived vascular) also stimulate PI3K, but it is unknown whether production of 3,4,5 phosphatidyinositol is sufficient to stimulate glucose transport in insulin-resistant muscle. |
| 2445 | 12663464 | Hence, we investigated the stimulation of PI3K and Akt-1, -2, and -3 by insulin and epidermal growth factors (EGFs) in skeletal muscles from lean and obese insulin-resistant humans. |
| 2446 | 12663464 | Insulin activated all Akt isoforms in lean muscles, whereas only Akt-1 was activated in obese muscles. |
| 2447 | 12663464 | Insulin receptor substrate (IRS)-1 was associated with PI3K activity, which is necessary for Akt activation by insulin, and was reduced in obese muscles, and this was accompanied by decreased IRS-1 expression. |
| 2448 | 12663464 | In contrast, insulin- or EGF-stimulated phosphotyrosine-associated PI3K activity was not different between lean and obese muscles. |
| 2449 | 12663464 | Defective signaling through Akt-2 and -3 but not Akt-1 in insulin-resistant human skeletal muscle: potential role in insulin resistance. |
| 2450 | 12663464 | Recent evidence has shown that activation of phosphatidyinositol-3-kinase (PI3K) and Akt, necessary for insulin stimulation of glucose transport, is impaired in insulin resistance. |
| 2451 | 12663464 | It is unknown, however, which Akt isoform shows impaired activation in insulin resistance. |
| 2452 | 12663464 | Additionally, related growth factors (epidermal or platelet-derived vascular) also stimulate PI3K, but it is unknown whether production of 3,4,5 phosphatidyinositol is sufficient to stimulate glucose transport in insulin-resistant muscle. |
| 2453 | 12663464 | Hence, we investigated the stimulation of PI3K and Akt-1, -2, and -3 by insulin and epidermal growth factors (EGFs) in skeletal muscles from lean and obese insulin-resistant humans. |
| 2454 | 12663464 | Insulin activated all Akt isoforms in lean muscles, whereas only Akt-1 was activated in obese muscles. |
| 2455 | 12663464 | Insulin receptor substrate (IRS)-1 was associated with PI3K activity, which is necessary for Akt activation by insulin, and was reduced in obese muscles, and this was accompanied by decreased IRS-1 expression. |
| 2456 | 12663464 | In contrast, insulin- or EGF-stimulated phosphotyrosine-associated PI3K activity was not different between lean and obese muscles. |
| 2457 | 12663464 | Defective signaling through Akt-2 and -3 but not Akt-1 in insulin-resistant human skeletal muscle: potential role in insulin resistance. |
| 2458 | 12663464 | Recent evidence has shown that activation of phosphatidyinositol-3-kinase (PI3K) and Akt, necessary for insulin stimulation of glucose transport, is impaired in insulin resistance. |
| 2459 | 12663464 | It is unknown, however, which Akt isoform shows impaired activation in insulin resistance. |
| 2460 | 12663464 | Additionally, related growth factors (epidermal or platelet-derived vascular) also stimulate PI3K, but it is unknown whether production of 3,4,5 phosphatidyinositol is sufficient to stimulate glucose transport in insulin-resistant muscle. |
| 2461 | 12663464 | Hence, we investigated the stimulation of PI3K and Akt-1, -2, and -3 by insulin and epidermal growth factors (EGFs) in skeletal muscles from lean and obese insulin-resistant humans. |
| 2462 | 12663464 | Insulin activated all Akt isoforms in lean muscles, whereas only Akt-1 was activated in obese muscles. |
| 2463 | 12663464 | Insulin receptor substrate (IRS)-1 was associated with PI3K activity, which is necessary for Akt activation by insulin, and was reduced in obese muscles, and this was accompanied by decreased IRS-1 expression. |
| 2464 | 12663464 | In contrast, insulin- or EGF-stimulated phosphotyrosine-associated PI3K activity was not different between lean and obese muscles. |
| 2465 | 12663464 | Defective signaling through Akt-2 and -3 but not Akt-1 in insulin-resistant human skeletal muscle: potential role in insulin resistance. |
| 2466 | 12663464 | Recent evidence has shown that activation of phosphatidyinositol-3-kinase (PI3K) and Akt, necessary for insulin stimulation of glucose transport, is impaired in insulin resistance. |
| 2467 | 12663464 | It is unknown, however, which Akt isoform shows impaired activation in insulin resistance. |
| 2468 | 12663464 | Additionally, related growth factors (epidermal or platelet-derived vascular) also stimulate PI3K, but it is unknown whether production of 3,4,5 phosphatidyinositol is sufficient to stimulate glucose transport in insulin-resistant muscle. |
| 2469 | 12663464 | Hence, we investigated the stimulation of PI3K and Akt-1, -2, and -3 by insulin and epidermal growth factors (EGFs) in skeletal muscles from lean and obese insulin-resistant humans. |
| 2470 | 12663464 | Insulin activated all Akt isoforms in lean muscles, whereas only Akt-1 was activated in obese muscles. |
| 2471 | 12663464 | Insulin receptor substrate (IRS)-1 was associated with PI3K activity, which is necessary for Akt activation by insulin, and was reduced in obese muscles, and this was accompanied by decreased IRS-1 expression. |
| 2472 | 12663464 | In contrast, insulin- or EGF-stimulated phosphotyrosine-associated PI3K activity was not different between lean and obese muscles. |
| 2473 | 12663464 | Defective signaling through Akt-2 and -3 but not Akt-1 in insulin-resistant human skeletal muscle: potential role in insulin resistance. |
| 2474 | 12663464 | Recent evidence has shown that activation of phosphatidyinositol-3-kinase (PI3K) and Akt, necessary for insulin stimulation of glucose transport, is impaired in insulin resistance. |
| 2475 | 12663464 | It is unknown, however, which Akt isoform shows impaired activation in insulin resistance. |
| 2476 | 12663464 | Additionally, related growth factors (epidermal or platelet-derived vascular) also stimulate PI3K, but it is unknown whether production of 3,4,5 phosphatidyinositol is sufficient to stimulate glucose transport in insulin-resistant muscle. |
| 2477 | 12663464 | Hence, we investigated the stimulation of PI3K and Akt-1, -2, and -3 by insulin and epidermal growth factors (EGFs) in skeletal muscles from lean and obese insulin-resistant humans. |
| 2478 | 12663464 | Insulin activated all Akt isoforms in lean muscles, whereas only Akt-1 was activated in obese muscles. |
| 2479 | 12663464 | Insulin receptor substrate (IRS)-1 was associated with PI3K activity, which is necessary for Akt activation by insulin, and was reduced in obese muscles, and this was accompanied by decreased IRS-1 expression. |
| 2480 | 12663464 | In contrast, insulin- or EGF-stimulated phosphotyrosine-associated PI3K activity was not different between lean and obese muscles. |
| 2481 | 12682423 | Apparently, both insulin and IGF-1 at physiological concentrations support cell survival by phosphatidylinositol 3 kinase-dependent and independent mechanisms. |
| 2482 | 12686100 | Semicarbazide-sensitive amine oxidase activity exerts insulin-like effects on glucose metabolism and insulin-signaling pathways in adipose cells. |
| 2483 | 12686100 | Semicarbazide-sensitive amine oxidase (SSAO) is very abundant at the plasma membrane in adipocytes. |
| 2484 | 12686100 | The combination of SSAO substrates and low concentrations of vanadate markedly stimulates glucose transport and GLUT4 glucose transporter recruitment to the cell surface in rat adipocytes by a mechanism that requires SSAO activity and hydrogen peroxide formation. |
| 2485 | 12686100 | Substrates of SSAO such as benzylamine or tyramine in combination with vanadate potently stimulate tyrosine phosphorylation of both insulin-receptor substrates 1 (IRS-1) and 3 (IRS-3) and phosphatidylinositol 3-kinase (PI 3-kinase) activity in adipose cells, which occurs in the presence of a weak stimulation of insulin-receptor kinase. |
| 2486 | 12686100 | Based on these observations, we propose that SSAO activity and vanadate potently mimic insulin effects in adipose cells and exert an anti-diabetic action in an animal model of type 1 diabetes mellitus. |
| 2487 | 12724332 | Characterization of insulin inhibition of transactivation by a C-terminal fragment of the forkhead transcription factor Foxo1 in rat hepatoma cells. |
| 2488 | 12724332 | In keeping with its important physiological roles, Foxo1 activity is negatively regulated in response to growth factors and cytokines that activate a phosphatidylinositol 3-kinase (PI 3-kinase) protein kinase B (PKB)/Akt pathway. |
| 2489 | 12724332 | PKB/Akt-mediated phosphorylation of Foxo1 has been shown to result in the inhibition of target gene transcription and to trigger the export of Foxo1 from the nucleus, which is generally believed to explain the subsequent decrease of transcription. |
| 2490 | 12724332 | In the present study, using a chimeric protein in which a C-terminal fragment of Foxo1 (amino acids 208-652) containing the transactivation domain is fused to the yeast Gal4 DNA binding domain, we present evidence showing that insulin can directly regulate transactivation by Foxo1 in H4IIE rat hepatoma cells. |
| 2491 | 12724332 | Insulin inhibition of Foxo1-(208-652)-stimulated transactivation is mediated by PI 3-kinase but in contrast to full-length Foxo1, does not require either of the two PKB/Akt phosphorylation sites (Ser253 and Ser316) present in the protein fragment. |
| 2492 | 12724332 | We conclude that the transcriptional activity of Foxo1 is regulated at different levels by insulin: transactivation, as well as DNA binding and nuclear exclusion. |
| 2493 | 12729803 | Insulin induces expression of adenosine kinase gene in rat lymphocytes by signaling through the mitogen-activated protein kinase pathway. |
| 2494 | 12729803 | Exposure of rat lymphocytes to wortmannin, an inhibitor of phosphatidylinositol 3-kinase (PI3K), or rapamycin, an inhibitor of mTOR, did not affect the ability of insulin to stimulate expression of AK. |
| 2495 | 12729803 | Prior treatment of the cells with 10 microM PD98059, an inhibitor of mitogen-activated protein kinase (MAPK) kinase (MEK) completely blocked insulin-stimulated expression of AK gene. |
| 2496 | 12729803 | Insulin produced a significant transient increase in the tyrosine phosphorylation of ERK1/2, and PD98059 inhibited this phosphorylation. |
| 2497 | 12729803 | Furthermore exposure of cells to insulin has resulted in transient phosphorylation of Elk-1 on Ser-383 and sustained elevation of c-Jun and c-Fos protein. |
| 2498 | 12729803 | This includes activation of the MAPK cascade and subsequent phosphorylation of Elk-1 followed by increased expression of c-fos and c-jun genes. |
| 2499 | 12730204 | As compared with the wild type, insulin-stimulated phosphorylation of the insulin receptor (IR) and insulin receptor substrate I was significantly reduced, and activities of phosphatidylinositol 3-kinase and glycogen synthase were low in transgenic muscle. |
| 2500 | 12730204 | In response to insulin, NEU3 was found to undergo tyrosine phosphorylation and subsequent association with the Grb2 protein, thus being activated and causing negative regulation of insulin signaling. |
| 2501 | 12730204 | In fact, accumulation of GM1 and GM2, the possible sialidase products in transgenic tissues, caused inhibition of IR phosphorylation in vitro, and blocking of association with Grb2 resulted in reversion of impaired insulin signaling in L6 cells. |
| 2502 | 12730204 | The data indicate that NEU3 indeed participates in the control of insulin signaling, probably via modulation of gangliosides and interaction with Grb2, and that the mice can serve as a valuable model for human insulin-resistant diabetes. |
| 2503 | 12730241 | Because the other known PH-PTB proteins (insulin receptor substrates: IRS-1, IRS-2, IRS-3, and IRS-4, and the downstream of kinases: DOK-1, DOK-2, and DOK-3) are substrates of insulin and insulin-like growth factor (IGF)-1 receptors, we asked whether these new proteins, termed IRS5/DOK4 and IRS6/DOK5, might also have roles in insulin and IGF-1 signaling. |
| 2504 | 12730241 | Both proteins are tyrosine-phosphorylated in response to insulin and IGF-1 in transfected cells, although the kinetics differ. |
| 2505 | 12730241 | Insulin receptor-phosphorylated IRS5/DOK4 associates with RasGAP, Crk, Src, and Fyn, but not phosphatidylinositol 3-kinase p85, Grb2, SHP-2, Nck, or phospholipase Cgamma Src homology 2 domains, and activates MAPK in cells. |
| 2506 | 12730241 | IRS5/DOK4 and IRS6/DOK5 represent two new signaling proteins with potential roles in insulin and IGF-1 action. |
| 2507 | 12734206 | Interaction of filamin A with the insulin receptor alters insulin-dependent activation of the mitogen-activated protein kinase pathway. |
| 2508 | 12734206 | Even though this event requires the participation of actin-binding proteins, the effect of filamin A (FLNa) on insulin-mediated signaling events is still unknown. |
| 2509 | 12734206 | We report here that human melanoma M2 cells lacking FLNa expression exhibited normal insulin receptor (IR) signaling, whereas FLNa-expressing A7 cells were unable to elicit insulin-dependent Shc tyrosine phosphorylation and p42/44 MAPK activation despite no significant defect in IR-stimulated phosphorylation of insulin receptor substrate-1 or activation of the phosphatidylinositol 3-kinase/AKT cascade. |
| 2510 | 12734206 | Insulin-dependent translocation of Shc, SOS1, and MAPK to lipid raft microdomains was markedly attenuated by FLNa expression. |
| 2511 | 12734206 | Coimmunoprecipitation experiments and in vitro binding assays demonstrated that FLNa binds constitutively to IR and that neither insulin nor depolymerization of actin by cytochalasin D affected this interaction. |
| 2512 | 12734206 | Ectopic expression of a C-terminal fragment of FLNa (FLNaCT) in HepG2 cells blocked the endogenous IR-FLNa interaction and potentiated insulin-stimulated MAPK phosphorylation and transactivation of Elk-1 compared with vector-transfected cells. |
| 2513 | 12734206 | Expression of FLNaCT had no major effect on insulin-induced phosphorylation of the IR, insulin receptor substrate-1, or AKT, but it elicited changes in actin cytoskeletal structure and ruffle formation in HepG2 cells. |
| 2514 | 12734206 | Taken together, these results indicate that FLNa interacts constitutively with the IR to exert an inhibitory tone along the MAPK activation pathway. |
| 2515 | 12765939 | Reduced activation of phosphatidylinositol-3 kinase and increased serine 636 phosphorylation of insulin receptor substrate-1 in primary culture of skeletal muscle cells from patients with type 2 diabetes. |
| 2516 | 12765939 | When compared with cells from control subjects, myotubes established from patients with type 2 diabetes presented the same defects as those previously evidenced in vivo in muscle biopsies, including defective stimulation of phosphatidylinositol (PI) 3-kinase activity, decreased association of PI 3-kinase with insulin receptor substrate (IRS)-1 and reduced IRS-1 tyrosine phosphorylation during insulin stimulation. |
| 2517 | 12765939 | In contrast to IRS-1, the signaling through IRS-2 was not altered. |
| 2518 | 12765939 | These results suggest that IRS-1 phosphorylation on serine 636 might be involved in the reduced phosphorylation of IRS-1 on tyrosine and in the subsequent alteration of insulin-induced PI 3-kinase activation. |
| 2519 | 12765939 | Moreover, increased MAPK activity seems to play a role in the phosphorylation of IRS-1 on serine residue in human muscle cells. |
| 2520 | 12767053 | Angiotensin converting enzyme (ACE) inhibitors are a widely used intervention for blood pressure control, and are particularly beneficial in hypertensive type 2 diabetic subjects with insulin resistance. |
| 2521 | 12767053 | The hemodynamic effects of ACE inhibitors are associated with enhanced levels of the vasodilator bradykinin and decreased production of the vasoconstrictor and growth factor angiotensin II (ATII). |
| 2522 | 12767053 | In insulin-resistant conditions, ACE inhibitors can also enhance whole-body glucose disposal and glucose transport activity in skeletal muscle. |
| 2523 | 12767053 | This review will focus on the metabolic consequences of ACE inhibition in insulin resistance. |
| 2524 | 12767053 | At the cellular level, ACE inhibitors acutely enhance glucose uptake in insulin-resistant skeletal muscle via two mechanisms. |
| 2525 | 12767053 | The acute actions of ACE inhibitors on skeletal muscle glucose transport are associated with upregulation of insulin signaling, including enhanced IRS-1 tyrosine phosphorylation and phosphatidylinositol-3-kinase activity, and ultimately with increased cell-surface GLUT-4 glucose transporter protein. |
| 2526 | 12767053 | Chronic administration of ACE inhibitors or AT(1) antagonists to insulin-resistant rodents can increase protein expression of GLUT-4 in skeletal muscle and myocardium. |
| 2527 | 12767053 | These data support the concept that ACE inhibitors can beneficially modulate glucose control in insulin-resistant states, possibly through a NO-dependent effect of bradykinin and/or antagonism of ATII action on skeletal muscle. |
| 2528 | 12790799 | It is possible that activation of protein kinase C (PKC) isoforms by free fatty acids (FFA) plays a role in the failure of pancreatic beta-cell mass expansion to compensate for peripheral insulin resistance in the pathogenesis of type-2 diabetes. |
| 2529 | 12790799 | The effect of lipid moieties on activation of conventional (PKC-alpha and -beta1), novel (PKC-delta) and atypical (PKC-zeta) PKC isoforms was evaluated in an in vitro assay, using biotinylated neurogranin as a substrate. |
| 2530 | 12790799 | It was found that FFA (0.4 mM oleate/complexed to 0.5% bovine serum albumin) inhibited IGF-I-induced activation of protein kinase B (PKB) in the pancreatic beta-cell line (INS-1), but this was alleviated in the presence of the general PKC inhibitor (Gö6850; 1 microM). |
| 2531 | 12790799 | To further investigate whether conventional or novel PKC isoforms adversely affect beta-cell proliferation, the effect of phorbol ester (phorbol 12-myristate 13-acetate; PMA)-mediated activation of these PKC isoforms on glucose/IGF-I-induced INS-1 cell mitogenesis, and insulin receptor substrate (IRS)-mediated signal transduction was investigated. |
| 2532 | 12790799 | PMA inhibited IGF-I-induced activation of PKB, correlating with inhibition of IGF-I-induced association of IRS-2 with the p85 regulatory subunit of phosphatidylinositol-3 kinase. |
| 2533 | 12790799 | Thus, FFA/PMA-induced activation of novel PKC isoforms can inhibit glucose/IGF-I-mediated beta-cell mitogenesis, in part by decreasing PKB activation, despite an upregulation of Erk1/2. |
| 2534 | 12807888 | Insulin is a potent inducer of adipogenesis, and differentiation of adipocytes requires many components of the insulin signaling pathway, including the insulin receptor substrate IRS-1 and phosphatidylinositol 3-kinase (PI3K). |
| 2535 | 12807888 | Likewise, overexpression of IR in control IRlox cells also results in inhibition of differentiation and a failure to accumulate expression of the adipogenic markers peroxisome proliferator-activated receptor gamma, Glut4, and fatty acid synthase, although cells overexpressing IR retain the ability to activate PI3K and down-regulate mitogen-activated protein kinase (MAPK) phosphorylation. |
| 2536 | 12807888 | Insulin is a potent inducer of adipogenesis, and differentiation of adipocytes requires many components of the insulin signaling pathway, including the insulin receptor substrate IRS-1 and phosphatidylinositol 3-kinase (PI3K). |
| 2537 | 12807888 | Likewise, overexpression of IR in control IRlox cells also results in inhibition of differentiation and a failure to accumulate expression of the adipogenic markers peroxisome proliferator-activated receptor gamma, Glut4, and fatty acid synthase, although cells overexpressing IR retain the ability to activate PI3K and down-regulate mitogen-activated protein kinase (MAPK) phosphorylation. |
| 2538 | 12829625 | Contraction-induced fatty acid translocase/CD36 translocation in rat cardiac myocytes is mediated through AMP-activated protein kinase signaling. |
| 2539 | 12829625 | Contraction of rat cardiac myocytes induces translocation of fatty acid translocase (FAT)/CD36 and GLUT4 from intracellular stores to the sarcolemma, leading to enhanced rates of long-chain fatty acid (FA) and glucose uptake, respectively. |
| 2540 | 12829625 | Because intracellular AMP/ATP is elevated in contracting cardiac myocytes, we investigated whether activation of AMP-activated protein kinase (AMP kinase) is involved in contraction-inducible FAT/CD36 translocation. |
| 2541 | 12829625 | Furthermore, the stimulating effects of both AICAR and oligomycin were antagonized by blocking FAT/CD36 with sulfo-N-succinimidylpalmitate, but not by inhibiting phosphatidylinositol 3-kinase with wortmannin, indicating the involvement of FAT/CD36, but excluding a role for insulin signaling. |
| 2542 | 12837666 | However, stretch had no effect on Akt in the slow-twitch soleus muscle, although there was a robust phosphorylation of the stress-activated protein kinase p38. |
| 2543 | 12837666 | Similar to contraction, stretch-induced Akt activation in the EDL was fully inhibited in the presence of the phosphatidylinositol 3-kinase inhibitor wortmannin, whereas glycogen synthase kinase-3 (GSK3) phosphorylation was only partially inhibited. |
| 2544 | 12871951 | Phosphatidylinositol 3'-kinase-dependent activation of renal mesangial cell Ki-Ras and ERK by advanced glycation end products. |
| 2545 | 12871951 | Here we show that treatment of mesangial cells with AGEs and with the receptor for AGEs agonist S100 triggers activation of the extracellular signal-regulated kinase (ERK) and phosphatidylinositol 3'-kinase (PI3K) pathways. |
| 2546 | 12871951 | Surprisingly, inhibition of PI3K blocks both ERK and Ki-Ras activation. |
| 2547 | 12871951 | We also observe that activation of ERK and the PI3K target kinase protein kinase-B is blocked with free radical scavengers, indicating a role for reactive oxygen species in AGE recruitment of PI3K. |
| 2548 | 12871951 | Thus, AGEs signal to Ki-Ras and ERK through reactive oxygen species-dependent activation of PI3K. |
| 2549 | 12871951 | Phosphatidylinositol 3'-kinase-dependent activation of renal mesangial cell Ki-Ras and ERK by advanced glycation end products. |
| 2550 | 12871951 | Here we show that treatment of mesangial cells with AGEs and with the receptor for AGEs agonist S100 triggers activation of the extracellular signal-regulated kinase (ERK) and phosphatidylinositol 3'-kinase (PI3K) pathways. |
| 2551 | 12871951 | Surprisingly, inhibition of PI3K blocks both ERK and Ki-Ras activation. |
| 2552 | 12871951 | We also observe that activation of ERK and the PI3K target kinase protein kinase-B is blocked with free radical scavengers, indicating a role for reactive oxygen species in AGE recruitment of PI3K. |
| 2553 | 12871951 | Thus, AGEs signal to Ki-Ras and ERK through reactive oxygen species-dependent activation of PI3K. |
| 2554 | 12871951 | Phosphatidylinositol 3'-kinase-dependent activation of renal mesangial cell Ki-Ras and ERK by advanced glycation end products. |
| 2555 | 12871951 | Here we show that treatment of mesangial cells with AGEs and with the receptor for AGEs agonist S100 triggers activation of the extracellular signal-regulated kinase (ERK) and phosphatidylinositol 3'-kinase (PI3K) pathways. |
| 2556 | 12871951 | Surprisingly, inhibition of PI3K blocks both ERK and Ki-Ras activation. |
| 2557 | 12871951 | We also observe that activation of ERK and the PI3K target kinase protein kinase-B is blocked with free radical scavengers, indicating a role for reactive oxygen species in AGE recruitment of PI3K. |
| 2558 | 12871951 | Thus, AGEs signal to Ki-Ras and ERK through reactive oxygen species-dependent activation of PI3K. |
| 2559 | 12871951 | Phosphatidylinositol 3'-kinase-dependent activation of renal mesangial cell Ki-Ras and ERK by advanced glycation end products. |
| 2560 | 12871951 | Here we show that treatment of mesangial cells with AGEs and with the receptor for AGEs agonist S100 triggers activation of the extracellular signal-regulated kinase (ERK) and phosphatidylinositol 3'-kinase (PI3K) pathways. |
| 2561 | 12871951 | Surprisingly, inhibition of PI3K blocks both ERK and Ki-Ras activation. |
| 2562 | 12871951 | We also observe that activation of ERK and the PI3K target kinase protein kinase-B is blocked with free radical scavengers, indicating a role for reactive oxygen species in AGE recruitment of PI3K. |
| 2563 | 12871951 | Thus, AGEs signal to Ki-Ras and ERK through reactive oxygen species-dependent activation of PI3K. |
| 2564 | 12882904 | Chronic endothelin-1 treatment leads to insulin resistance in vivo. |
| 2565 | 12882904 | We determined whether chronic endothelin-1 (ET-1) treatment could lead to in vivo insulin resistance. |
| 2566 | 12882904 | Like insulin, ET-1 acutely stimulated glucose transport in isolated soleus muscle strips of WKY rats. |
| 2567 | 12882904 | ET-1 pretreatment (1 h) decreased insulin-stimulated glucose transport in muscle strips (-23%). |
| 2568 | 12882904 | Subsequent hyperinsulinemic-euglycemic clamps showed that ET-1 treatment led to an approximately 30% decrease in insulin-stimulated glucose disposal rates in male and female rats. |
| 2569 | 12882904 | With respect to insulin signaling, chronic in vivo ET-1 treatment led to a 30-40% decrease in IRS-I protein content, IRS-I-associated p110(alpha), and AKT activation. |
| 2570 | 12882904 | In summary, 1) in vitro ET-1 pretreatment leads to decreased insulin-stimulated glucose transport in skeletal muscle strips; 2) chronic ET-1 administration in vivo leads to whole-body insulin resistance, with decreased skeletal muscle glucose transport and impaired insulin signaling; and 3) elevated ET-1 levels may be a cause of insulin resistance in certain pathophysiologic states. |
| 2571 | 12882906 | There is evidence suggesting there are separate insulin- and contraction-stimulated pools of GLUT4-containing vesicles. |
| 2572 | 12882906 | Stimulation of glucose transport and GLUT4 translocation by bpV(phen) was completely blocked by the phosphatidylinositol 3-kinase (PI 3-K) inhibitors wortmannin and LY294002. |
| 2573 | 12882906 | Our results suggest that the GLUT4 vesicles that are normally translocated in response to contractions but not insulin can respond to the signal generated via the IRS-PI 3-K pathway if it is sufficiently powerful. |
| 2574 | 12882908 | Insulin-stimulated protein kinase C lambda/zeta activity is reduced in skeletal muscle of humans with obesity and type 2 diabetes: reversal with weight reduction. |
| 2575 | 12882908 | The atypical protein kinase C (PKC) isoforms lambda and zeta are downstream of phosphatidylinositol-3 kinase (PI3K) and are required for maximal insulin stimulation of glucose uptake. |
| 2576 | 12882908 | Phosphoinositide-dependent protein kinase-1 (PDK-1), also downstream of PI3K, mediates activation of atypical PKC isoforms and Akt. |
| 2577 | 12882908 | To determine whether impaired PKClambda/zeta or PDK-1 activation plays a role in the pathogenesis of insulin resistance, we measured the activities of PKClambda/zeta and PDK-1 in vastus lateralis muscle of lean, obese, and obese/type 2 diabetic humans. |
| 2578 | 12882908 | Insulin-stimulated insulin receptor substrate (IRS)-1 tyrosine phosphorylation and PI3K activity are impaired 40-50% in diabetic subjects compared with lean or obese subjects. |
| 2579 | 12882908 | Importantly, weight loss in obese subjects normalizes PKClambda/zeta activation and increases IRS-1 phosphorylation and PI3K activity. |
| 2580 | 12882908 | Insulin also stimulates PDK-1 activity approximately twofold with no impairment in obese or diabetic subjects. |
| 2581 | 12882908 | In contrast to our previous data on Akt, reduced insulin-stimulated PKClambda/zeta activity could play a role in the pathogenesis of insulin resistance in muscle of obese and type 2 diabetic subjects. |
| 2582 | 12882908 | Insulin-stimulated protein kinase C lambda/zeta activity is reduced in skeletal muscle of humans with obesity and type 2 diabetes: reversal with weight reduction. |
| 2583 | 12882908 | The atypical protein kinase C (PKC) isoforms lambda and zeta are downstream of phosphatidylinositol-3 kinase (PI3K) and are required for maximal insulin stimulation of glucose uptake. |
| 2584 | 12882908 | Phosphoinositide-dependent protein kinase-1 (PDK-1), also downstream of PI3K, mediates activation of atypical PKC isoforms and Akt. |
| 2585 | 12882908 | To determine whether impaired PKClambda/zeta or PDK-1 activation plays a role in the pathogenesis of insulin resistance, we measured the activities of PKClambda/zeta and PDK-1 in vastus lateralis muscle of lean, obese, and obese/type 2 diabetic humans. |
| 2586 | 12882908 | Insulin-stimulated insulin receptor substrate (IRS)-1 tyrosine phosphorylation and PI3K activity are impaired 40-50% in diabetic subjects compared with lean or obese subjects. |
| 2587 | 12882908 | Importantly, weight loss in obese subjects normalizes PKClambda/zeta activation and increases IRS-1 phosphorylation and PI3K activity. |
| 2588 | 12882908 | Insulin also stimulates PDK-1 activity approximately twofold with no impairment in obese or diabetic subjects. |
| 2589 | 12882908 | In contrast to our previous data on Akt, reduced insulin-stimulated PKClambda/zeta activity could play a role in the pathogenesis of insulin resistance in muscle of obese and type 2 diabetic subjects. |
| 2590 | 12882908 | Insulin-stimulated protein kinase C lambda/zeta activity is reduced in skeletal muscle of humans with obesity and type 2 diabetes: reversal with weight reduction. |
| 2591 | 12882908 | The atypical protein kinase C (PKC) isoforms lambda and zeta are downstream of phosphatidylinositol-3 kinase (PI3K) and are required for maximal insulin stimulation of glucose uptake. |
| 2592 | 12882908 | Phosphoinositide-dependent protein kinase-1 (PDK-1), also downstream of PI3K, mediates activation of atypical PKC isoforms and Akt. |
| 2593 | 12882908 | To determine whether impaired PKClambda/zeta or PDK-1 activation plays a role in the pathogenesis of insulin resistance, we measured the activities of PKClambda/zeta and PDK-1 in vastus lateralis muscle of lean, obese, and obese/type 2 diabetic humans. |
| 2594 | 12882908 | Insulin-stimulated insulin receptor substrate (IRS)-1 tyrosine phosphorylation and PI3K activity are impaired 40-50% in diabetic subjects compared with lean or obese subjects. |
| 2595 | 12882908 | Importantly, weight loss in obese subjects normalizes PKClambda/zeta activation and increases IRS-1 phosphorylation and PI3K activity. |
| 2596 | 12882908 | Insulin also stimulates PDK-1 activity approximately twofold with no impairment in obese or diabetic subjects. |
| 2597 | 12882908 | In contrast to our previous data on Akt, reduced insulin-stimulated PKClambda/zeta activity could play a role in the pathogenesis of insulin resistance in muscle of obese and type 2 diabetic subjects. |
| 2598 | 12882908 | Insulin-stimulated protein kinase C lambda/zeta activity is reduced in skeletal muscle of humans with obesity and type 2 diabetes: reversal with weight reduction. |
| 2599 | 12882908 | The atypical protein kinase C (PKC) isoforms lambda and zeta are downstream of phosphatidylinositol-3 kinase (PI3K) and are required for maximal insulin stimulation of glucose uptake. |
| 2600 | 12882908 | Phosphoinositide-dependent protein kinase-1 (PDK-1), also downstream of PI3K, mediates activation of atypical PKC isoforms and Akt. |
| 2601 | 12882908 | To determine whether impaired PKClambda/zeta or PDK-1 activation plays a role in the pathogenesis of insulin resistance, we measured the activities of PKClambda/zeta and PDK-1 in vastus lateralis muscle of lean, obese, and obese/type 2 diabetic humans. |
| 2602 | 12882908 | Insulin-stimulated insulin receptor substrate (IRS)-1 tyrosine phosphorylation and PI3K activity are impaired 40-50% in diabetic subjects compared with lean or obese subjects. |
| 2603 | 12882908 | Importantly, weight loss in obese subjects normalizes PKClambda/zeta activation and increases IRS-1 phosphorylation and PI3K activity. |
| 2604 | 12882908 | Insulin also stimulates PDK-1 activity approximately twofold with no impairment in obese or diabetic subjects. |
| 2605 | 12882908 | In contrast to our previous data on Akt, reduced insulin-stimulated PKClambda/zeta activity could play a role in the pathogenesis of insulin resistance in muscle of obese and type 2 diabetic subjects. |
| 2606 | 12898468 | Physical exercise enhances protein kinase C delta activity and insulin receptor tyrosine phosphorylation in diabetes-prone psammomys obesus. |
| 2607 | 12898468 | In the present study we characterized the effect of physical exercise on protein kinase C delta (PKC delta) activity, as a mediator of the insulin-signaling cascade in vivo. |
| 2608 | 12898468 | Tyrosine phosphorylation of insulin receptor (IR), insulin receptor substrate-1 (IRS-1), and phosphatidylinositol 3 kinase (PI3 kinase) was significantly higher in the HE/EX and LE/C groups compared with the HE/C group. |
| 2609 | 12909611 | Exercise synergistically enhanced insulin-stimulated insulin receptor substrate 1-associated phosphatidylinositol 3-kinase activity (P < 0.05) and Akt Ser473 phosphorylation (P < 0.05) in nondiabetic subjects but had little effect in diabetic subjects. |
| 2610 | 12909611 | In nondiabetic, but not diabetic, subjects, exercise-induced enhancement of insulin stimulation of the phosphatidylinositol 3-kinase pathway is also likely to be involved in the exercise-induced synergistic enhancement of glucose disposal. |
| 2611 | 12909611 | Exercise synergistically enhanced insulin-stimulated insulin receptor substrate 1-associated phosphatidylinositol 3-kinase activity (P < 0.05) and Akt Ser473 phosphorylation (P < 0.05) in nondiabetic subjects but had little effect in diabetic subjects. |
| 2612 | 12909611 | In nondiabetic, but not diabetic, subjects, exercise-induced enhancement of insulin stimulation of the phosphatidylinositol 3-kinase pathway is also likely to be involved in the exercise-induced synergistic enhancement of glucose disposal. |
| 2613 | 12928438 | AR-A014418 protects N2A neuroblastoma cells against cell death mediated by inhibition of the phosphatidylinositol 3-kinase/protein kinase B survival pathway. |
| 2614 | 12944390 | Preincubation of cells with wortmannin (phosphatidylinositol 3-kinase inhibitor) blocked only adiponectin- but not LPA-mediated production of NO. |
| 2615 | 12944390 | Using phospho-specific antibodies, we observed that either adiponectin or insulin treatment (but not LPA treatment) caused phosphorylation of both Akt at Ser473 and endothelial nitric-oxide synthase (eNOS) at Ser1179 that was inhibitable by wortmannin. |
| 2616 | 12944390 | We next transfected bovine aortic endothelial cells with dominant-inhibitory mutants of Akt (Akt-AAA) or AMP-activated protein kinase (AMPK) (AMPKK45R). |
| 2617 | 12944390 | Moreover, AMPK-K45R inhibited phosphorylation of eNOS at Ser1179 in response to adiponectin but not in response to insulin. |
| 2618 | 12944390 | We conclude that adiponectin has novel vascular actions to directly stimulate production of NO in endothelial cells using phosphatidylinositol 3-kinase-dependent pathways involving phosphorylation of eNOS at Ser1179 by AMPK. |
| 2619 | 12944390 | Thus, the effects of adiponectin to augment metabolic actions of insulin in vivo may be due, in part, to vasodilator actions of adiponectin. |
| 2620 | 12944390 | Preincubation of cells with wortmannin (phosphatidylinositol 3-kinase inhibitor) blocked only adiponectin- but not LPA-mediated production of NO. |
| 2621 | 12944390 | Using phospho-specific antibodies, we observed that either adiponectin or insulin treatment (but not LPA treatment) caused phosphorylation of both Akt at Ser473 and endothelial nitric-oxide synthase (eNOS) at Ser1179 that was inhibitable by wortmannin. |
| 2622 | 12944390 | We next transfected bovine aortic endothelial cells with dominant-inhibitory mutants of Akt (Akt-AAA) or AMP-activated protein kinase (AMPK) (AMPKK45R). |
| 2623 | 12944390 | Moreover, AMPK-K45R inhibited phosphorylation of eNOS at Ser1179 in response to adiponectin but not in response to insulin. |
| 2624 | 12944390 | We conclude that adiponectin has novel vascular actions to directly stimulate production of NO in endothelial cells using phosphatidylinositol 3-kinase-dependent pathways involving phosphorylation of eNOS at Ser1179 by AMPK. |
| 2625 | 12944390 | Thus, the effects of adiponectin to augment metabolic actions of insulin in vivo may be due, in part, to vasodilator actions of adiponectin. |
| 2626 | 12960377 | Stearoyl-CoA desaturase 1 deficiency elevates insulin-signaling components and down-regulates protein-tyrosine phosphatase 1B in muscle. |
| 2627 | 12960377 | We have shown previously that mice with a targeted disruption in the stearoyl-CoA desaturase 1 gene (SCD1-/-) have increased insulin sensitivity compared with control mice. |
| 2628 | 12960377 | Here we show that the SCD1-/- mice have increased insulin signaling in muscle. |
| 2629 | 12960377 | The tyrosine phosphorylation of insulin-like growth factor-1 receptor was similar between SCD1+/+ and SCD1-/- mice. |
| 2630 | 12960377 | The association of insulin receptor substrates 1 and 2 with alphap85 subunit of phosphatidylinositol 3-kinase as well as the phosphorylation of Akt-Ser-473 and Akt-Thr-308 are also elevated in the SCD1-/- mice. |
| 2631 | 12960377 | Interestingly, the mRNA levels, protein mass, and activity of the protein-tyrosine phosphatase-1B implicated in the attenuation of the insulin signal are reduced in the SCD1-/- mice, whereas the levels of the leukocyte antigen-related protein phosphatase are similar between two groups of mice. |
| 2632 | 12960377 | The content of glucose transporter 4 in the plasma membrane and basal as well as insulin-mediated glucose uptake are increased in the SCD1-/- mice. |
| 2633 | 12960377 | We hypothesize that loss of SCD1 function induces increased insulin signaling at least in part by a reduction in the expression of protein-tyrosine phosphatase 1B. |
| 2634 | 12970360 | Human glycated albumin affects glucose metabolism in L6 skeletal muscle cells by impairing insulin-induced insulin receptor substrate (IRS) signaling through a protein kinase C alpha-mediated mechanism. |
| 2635 | 12970360 | Here, we have investigated the action of human glycated albumin (HGA) on insulin signaling in L6 skeletal muscle cells. |
| 2636 | 12970360 | Further, HGA reduced insulin-stimulated serine phosphorylation of PKB and GSK3, but did not alter ERK1/2 activation. |
| 2637 | 12970360 | HGA did not affect either insulin receptor kinase activity or insulin-induced Shc phosphorylation on tyrosine. |
| 2638 | 12970360 | In contrast, insulin-dependent IRS-1 and IRS-2 tyrosine phosphorylation was severely reduced in cells preincubated with HGA for 24 h. |
| 2639 | 12970360 | Insulin-stimulated association of PI3K with IRS-1 and IRS-2, and PI3K activity were reduced by HGA in parallel with the changes in IRS tyrosine phosphorylation, while Grb2-IRS association was unchanged. |
| 2640 | 12970360 | In L6 myotubes, exposure to HGA increased PKC activity by 2-fold resulting in a similar increase in Ser/Thr phosphorylation of IRS-1 and IRS-2. |
| 2641 | 12970360 | BDM also blocked the action of HGA on insulin-stimulated PKB and GSK3 alpha. |
| 2642 | 12975478 | PKClambda is implicated as a downstream effector of PI3K in insulin action. |
| 2643 | 12975478 | We show here that mice that lack PKClambda specifically in the liver (L-lambdaKO mice), produced with the use of the Cre-loxP system, exhibit increased insulin sensitivity as well as a decreased triglyceride content and reduced expression of the sterol regulatory element-binding protein-1c (SREBP-1c) gene in the liver. |
| 2644 | 12975478 | Expression of Srebp1c induced by insulin or by active PI3K in primary cultured rat hepatocytes was inhibited by a dominant-negative form of PKClambda and was mimicked by overexpression of WT PKClambda. |
| 2645 | 12975478 | PKClambda is implicated as a downstream effector of PI3K in insulin action. |
| 2646 | 12975478 | We show here that mice that lack PKClambda specifically in the liver (L-lambdaKO mice), produced with the use of the Cre-loxP system, exhibit increased insulin sensitivity as well as a decreased triglyceride content and reduced expression of the sterol regulatory element-binding protein-1c (SREBP-1c) gene in the liver. |
| 2647 | 12975478 | Expression of Srebp1c induced by insulin or by active PI3K in primary cultured rat hepatocytes was inhibited by a dominant-negative form of PKClambda and was mimicked by overexpression of WT PKClambda. |
| 2648 | 14514640 | Inhibition of net HepG2 cell apolipoprotein B secretion by the citrus flavonoid naringenin involves activation of phosphatidylinositol 3-kinase, independent of insulin receptor substrate-1 phosphorylation. |
| 2649 | 14514640 | In HepG2 human hepatoma cells, naringenin inhibits apolipoprotein B (apoB) secretion primarily by inhibiting microsomal triglyceride transfer protein and enhances LDL receptor (LDLr)-mediated apoB-containing lipoprotein uptake. |
| 2650 | 14514640 | Phosphatidylinositol 3-kinase (PI3K) activation by insulin increases sterol regulatory element-binding protein (SREBP)-1 and LDLr expression and inhibits apoB secretion in hepatocytes. |
| 2651 | 14514640 | Insulin and naringenin induced PI3K-dependent increases in cytosolic and nuclear SREBP-1 and LDLr expression. |
| 2652 | 14514640 | Similar PI3K-mediated increases in SREBP-1 were observed in McA-RH7777 rat hepatoma cells, which express predominantly SREBP-1c. |
| 2653 | 14514640 | Reductions in HepG2 cell media apoB with naringenin were partially attenuated by wortmannin, whereas the effect of insulin was completely blocked. |
| 2654 | 14514640 | Both treatments reduced apoB100 secretion in wild-type and LDLr(-/-) mouse hepatocytes to the same extent. |
| 2655 | 14514640 | Insulin and naringenin increased HepG2 cell PI3K activity and decreased insulin receptor substrate (IRS)-2 levels. |
| 2656 | 14514640 | In sharp contrast to insulin, naringenin did not induce tyrosine phosphorylation of IRS-1. |
| 2657 | 14514640 | We conclude that naringenin increases LDLr expression in HepG2 cells via PI3K-mediated upregulation of SREBP-1, independent of IRS-1 phosphorylation. |
| 2658 | 14514640 | Although this pathway may not regulate apoB secretion in primary hepatocytes, PI3K activation by this novel mechanism may explain the insulin-like effects of naringenin in vivo. |
| 2659 | 14514640 | Inhibition of net HepG2 cell apolipoprotein B secretion by the citrus flavonoid naringenin involves activation of phosphatidylinositol 3-kinase, independent of insulin receptor substrate-1 phosphorylation. |
| 2660 | 14514640 | In HepG2 human hepatoma cells, naringenin inhibits apolipoprotein B (apoB) secretion primarily by inhibiting microsomal triglyceride transfer protein and enhances LDL receptor (LDLr)-mediated apoB-containing lipoprotein uptake. |
| 2661 | 14514640 | Phosphatidylinositol 3-kinase (PI3K) activation by insulin increases sterol regulatory element-binding protein (SREBP)-1 and LDLr expression and inhibits apoB secretion in hepatocytes. |
| 2662 | 14514640 | Insulin and naringenin induced PI3K-dependent increases in cytosolic and nuclear SREBP-1 and LDLr expression. |
| 2663 | 14514640 | Similar PI3K-mediated increases in SREBP-1 were observed in McA-RH7777 rat hepatoma cells, which express predominantly SREBP-1c. |
| 2664 | 14514640 | Reductions in HepG2 cell media apoB with naringenin were partially attenuated by wortmannin, whereas the effect of insulin was completely blocked. |
| 2665 | 14514640 | Both treatments reduced apoB100 secretion in wild-type and LDLr(-/-) mouse hepatocytes to the same extent. |
| 2666 | 14514640 | Insulin and naringenin increased HepG2 cell PI3K activity and decreased insulin receptor substrate (IRS)-2 levels. |
| 2667 | 14514640 | In sharp contrast to insulin, naringenin did not induce tyrosine phosphorylation of IRS-1. |
| 2668 | 14514640 | We conclude that naringenin increases LDLr expression in HepG2 cells via PI3K-mediated upregulation of SREBP-1, independent of IRS-1 phosphorylation. |
| 2669 | 14514640 | Although this pathway may not regulate apoB secretion in primary hepatocytes, PI3K activation by this novel mechanism may explain the insulin-like effects of naringenin in vivo. |
| 2670 | 14514640 | Inhibition of net HepG2 cell apolipoprotein B secretion by the citrus flavonoid naringenin involves activation of phosphatidylinositol 3-kinase, independent of insulin receptor substrate-1 phosphorylation. |
| 2671 | 14514640 | In HepG2 human hepatoma cells, naringenin inhibits apolipoprotein B (apoB) secretion primarily by inhibiting microsomal triglyceride transfer protein and enhances LDL receptor (LDLr)-mediated apoB-containing lipoprotein uptake. |
| 2672 | 14514640 | Phosphatidylinositol 3-kinase (PI3K) activation by insulin increases sterol regulatory element-binding protein (SREBP)-1 and LDLr expression and inhibits apoB secretion in hepatocytes. |
| 2673 | 14514640 | Insulin and naringenin induced PI3K-dependent increases in cytosolic and nuclear SREBP-1 and LDLr expression. |
| 2674 | 14514640 | Similar PI3K-mediated increases in SREBP-1 were observed in McA-RH7777 rat hepatoma cells, which express predominantly SREBP-1c. |
| 2675 | 14514640 | Reductions in HepG2 cell media apoB with naringenin were partially attenuated by wortmannin, whereas the effect of insulin was completely blocked. |
| 2676 | 14514640 | Both treatments reduced apoB100 secretion in wild-type and LDLr(-/-) mouse hepatocytes to the same extent. |
| 2677 | 14514640 | Insulin and naringenin increased HepG2 cell PI3K activity and decreased insulin receptor substrate (IRS)-2 levels. |
| 2678 | 14514640 | In sharp contrast to insulin, naringenin did not induce tyrosine phosphorylation of IRS-1. |
| 2679 | 14514640 | We conclude that naringenin increases LDLr expression in HepG2 cells via PI3K-mediated upregulation of SREBP-1, independent of IRS-1 phosphorylation. |
| 2680 | 14514640 | Although this pathway may not regulate apoB secretion in primary hepatocytes, PI3K activation by this novel mechanism may explain the insulin-like effects of naringenin in vivo. |
| 2681 | 14514640 | Inhibition of net HepG2 cell apolipoprotein B secretion by the citrus flavonoid naringenin involves activation of phosphatidylinositol 3-kinase, independent of insulin receptor substrate-1 phosphorylation. |
| 2682 | 14514640 | In HepG2 human hepatoma cells, naringenin inhibits apolipoprotein B (apoB) secretion primarily by inhibiting microsomal triglyceride transfer protein and enhances LDL receptor (LDLr)-mediated apoB-containing lipoprotein uptake. |
| 2683 | 14514640 | Phosphatidylinositol 3-kinase (PI3K) activation by insulin increases sterol regulatory element-binding protein (SREBP)-1 and LDLr expression and inhibits apoB secretion in hepatocytes. |
| 2684 | 14514640 | Insulin and naringenin induced PI3K-dependent increases in cytosolic and nuclear SREBP-1 and LDLr expression. |
| 2685 | 14514640 | Similar PI3K-mediated increases in SREBP-1 were observed in McA-RH7777 rat hepatoma cells, which express predominantly SREBP-1c. |
| 2686 | 14514640 | Reductions in HepG2 cell media apoB with naringenin were partially attenuated by wortmannin, whereas the effect of insulin was completely blocked. |
| 2687 | 14514640 | Both treatments reduced apoB100 secretion in wild-type and LDLr(-/-) mouse hepatocytes to the same extent. |
| 2688 | 14514640 | Insulin and naringenin increased HepG2 cell PI3K activity and decreased insulin receptor substrate (IRS)-2 levels. |
| 2689 | 14514640 | In sharp contrast to insulin, naringenin did not induce tyrosine phosphorylation of IRS-1. |
| 2690 | 14514640 | We conclude that naringenin increases LDLr expression in HepG2 cells via PI3K-mediated upregulation of SREBP-1, independent of IRS-1 phosphorylation. |
| 2691 | 14514640 | Although this pathway may not regulate apoB secretion in primary hepatocytes, PI3K activation by this novel mechanism may explain the insulin-like effects of naringenin in vivo. |
| 2692 | 14514640 | Inhibition of net HepG2 cell apolipoprotein B secretion by the citrus flavonoid naringenin involves activation of phosphatidylinositol 3-kinase, independent of insulin receptor substrate-1 phosphorylation. |
| 2693 | 14514640 | In HepG2 human hepatoma cells, naringenin inhibits apolipoprotein B (apoB) secretion primarily by inhibiting microsomal triglyceride transfer protein and enhances LDL receptor (LDLr)-mediated apoB-containing lipoprotein uptake. |
| 2694 | 14514640 | Phosphatidylinositol 3-kinase (PI3K) activation by insulin increases sterol regulatory element-binding protein (SREBP)-1 and LDLr expression and inhibits apoB secretion in hepatocytes. |
| 2695 | 14514640 | Insulin and naringenin induced PI3K-dependent increases in cytosolic and nuclear SREBP-1 and LDLr expression. |
| 2696 | 14514640 | Similar PI3K-mediated increases in SREBP-1 were observed in McA-RH7777 rat hepatoma cells, which express predominantly SREBP-1c. |
| 2697 | 14514640 | Reductions in HepG2 cell media apoB with naringenin were partially attenuated by wortmannin, whereas the effect of insulin was completely blocked. |
| 2698 | 14514640 | Both treatments reduced apoB100 secretion in wild-type and LDLr(-/-) mouse hepatocytes to the same extent. |
| 2699 | 14514640 | Insulin and naringenin increased HepG2 cell PI3K activity and decreased insulin receptor substrate (IRS)-2 levels. |
| 2700 | 14514640 | In sharp contrast to insulin, naringenin did not induce tyrosine phosphorylation of IRS-1. |
| 2701 | 14514640 | We conclude that naringenin increases LDLr expression in HepG2 cells via PI3K-mediated upregulation of SREBP-1, independent of IRS-1 phosphorylation. |
| 2702 | 14514640 | Although this pathway may not regulate apoB secretion in primary hepatocytes, PI3K activation by this novel mechanism may explain the insulin-like effects of naringenin in vivo. |
| 2703 | 14514640 | Inhibition of net HepG2 cell apolipoprotein B secretion by the citrus flavonoid naringenin involves activation of phosphatidylinositol 3-kinase, independent of insulin receptor substrate-1 phosphorylation. |
| 2704 | 14514640 | In HepG2 human hepatoma cells, naringenin inhibits apolipoprotein B (apoB) secretion primarily by inhibiting microsomal triglyceride transfer protein and enhances LDL receptor (LDLr)-mediated apoB-containing lipoprotein uptake. |
| 2705 | 14514640 | Phosphatidylinositol 3-kinase (PI3K) activation by insulin increases sterol regulatory element-binding protein (SREBP)-1 and LDLr expression and inhibits apoB secretion in hepatocytes. |
| 2706 | 14514640 | Insulin and naringenin induced PI3K-dependent increases in cytosolic and nuclear SREBP-1 and LDLr expression. |
| 2707 | 14514640 | Similar PI3K-mediated increases in SREBP-1 were observed in McA-RH7777 rat hepatoma cells, which express predominantly SREBP-1c. |
| 2708 | 14514640 | Reductions in HepG2 cell media apoB with naringenin were partially attenuated by wortmannin, whereas the effect of insulin was completely blocked. |
| 2709 | 14514640 | Both treatments reduced apoB100 secretion in wild-type and LDLr(-/-) mouse hepatocytes to the same extent. |
| 2710 | 14514640 | Insulin and naringenin increased HepG2 cell PI3K activity and decreased insulin receptor substrate (IRS)-2 levels. |
| 2711 | 14514640 | In sharp contrast to insulin, naringenin did not induce tyrosine phosphorylation of IRS-1. |
| 2712 | 14514640 | We conclude that naringenin increases LDLr expression in HepG2 cells via PI3K-mediated upregulation of SREBP-1, independent of IRS-1 phosphorylation. |
| 2713 | 14514640 | Although this pathway may not regulate apoB secretion in primary hepatocytes, PI3K activation by this novel mechanism may explain the insulin-like effects of naringenin in vivo. |
| 2714 | 14514640 | Inhibition of net HepG2 cell apolipoprotein B secretion by the citrus flavonoid naringenin involves activation of phosphatidylinositol 3-kinase, independent of insulin receptor substrate-1 phosphorylation. |
| 2715 | 14514640 | In HepG2 human hepatoma cells, naringenin inhibits apolipoprotein B (apoB) secretion primarily by inhibiting microsomal triglyceride transfer protein and enhances LDL receptor (LDLr)-mediated apoB-containing lipoprotein uptake. |
| 2716 | 14514640 | Phosphatidylinositol 3-kinase (PI3K) activation by insulin increases sterol regulatory element-binding protein (SREBP)-1 and LDLr expression and inhibits apoB secretion in hepatocytes. |
| 2717 | 14514640 | Insulin and naringenin induced PI3K-dependent increases in cytosolic and nuclear SREBP-1 and LDLr expression. |
| 2718 | 14514640 | Similar PI3K-mediated increases in SREBP-1 were observed in McA-RH7777 rat hepatoma cells, which express predominantly SREBP-1c. |
| 2719 | 14514640 | Reductions in HepG2 cell media apoB with naringenin were partially attenuated by wortmannin, whereas the effect of insulin was completely blocked. |
| 2720 | 14514640 | Both treatments reduced apoB100 secretion in wild-type and LDLr(-/-) mouse hepatocytes to the same extent. |
| 2721 | 14514640 | Insulin and naringenin increased HepG2 cell PI3K activity and decreased insulin receptor substrate (IRS)-2 levels. |
| 2722 | 14514640 | In sharp contrast to insulin, naringenin did not induce tyrosine phosphorylation of IRS-1. |
| 2723 | 14514640 | We conclude that naringenin increases LDLr expression in HepG2 cells via PI3K-mediated upregulation of SREBP-1, independent of IRS-1 phosphorylation. |
| 2724 | 14514640 | Although this pathway may not regulate apoB secretion in primary hepatocytes, PI3K activation by this novel mechanism may explain the insulin-like effects of naringenin in vivo. |
| 2725 | 14514641 | The mechanisms by which insulin exerts these contrasting effects were examined using alpha-smooth muscle actin (alpha-SMA) as a marker of VSMC phenotype because alpha-SMA is highly expressed in quiescent but not migratory VSMC. |
| 2726 | 14514641 | Wortmannin, a phosphatidylinositol 3-kinase (PI3K) inhibitor, decreased insulin-stimulated expression of alpha-SMA mRNA by 26% and protein by 48% but had no effect on VSMC migration. |
| 2727 | 14514641 | PD98059, a mitogen-activated protein kinase (MAPK) kinase inhibitor, decreased insulin-induced VSMC migration by 52% but did not affect alpha-SMA levels. |
| 2728 | 14514641 | Platelet-derived growth factor (PDGF) promoted dedifferentiation of VSMC, and insulin counteracted this effect. |
| 2729 | 14514641 | Furthermore, insulin increased alpha-SMA mRNA and protein levels to 111 and 118%, respectively, after PDGF-induced dedifferentiation, an effect inhibited by wortmannin. |
| 2730 | 14514641 | In conclusion, insulin's ability to maintain VSMC quiescence and reverse the dedifferentiating influence of PDGF is mediated via the PI3K pathway, whereas insulin promotes VSMC migration via the MAPK pathway. |
| 2731 | 14514641 | Thus, with impaired PI 3-kinase signaling and intact MAPK signaling, as seen in insulin resistance, insulin may lose its ability to maintain VSMC quiescence and instead promote VSMC migration. |
| 2732 | 14514641 | The mechanisms by which insulin exerts these contrasting effects were examined using alpha-smooth muscle actin (alpha-SMA) as a marker of VSMC phenotype because alpha-SMA is highly expressed in quiescent but not migratory VSMC. |
| 2733 | 14514641 | Wortmannin, a phosphatidylinositol 3-kinase (PI3K) inhibitor, decreased insulin-stimulated expression of alpha-SMA mRNA by 26% and protein by 48% but had no effect on VSMC migration. |
| 2734 | 14514641 | PD98059, a mitogen-activated protein kinase (MAPK) kinase inhibitor, decreased insulin-induced VSMC migration by 52% but did not affect alpha-SMA levels. |
| 2735 | 14514641 | Platelet-derived growth factor (PDGF) promoted dedifferentiation of VSMC, and insulin counteracted this effect. |
| 2736 | 14514641 | Furthermore, insulin increased alpha-SMA mRNA and protein levels to 111 and 118%, respectively, after PDGF-induced dedifferentiation, an effect inhibited by wortmannin. |
| 2737 | 14514641 | In conclusion, insulin's ability to maintain VSMC quiescence and reverse the dedifferentiating influence of PDGF is mediated via the PI3K pathway, whereas insulin promotes VSMC migration via the MAPK pathway. |
| 2738 | 14514641 | Thus, with impaired PI 3-kinase signaling and intact MAPK signaling, as seen in insulin resistance, insulin may lose its ability to maintain VSMC quiescence and instead promote VSMC migration. |
| 2739 | 14516785 | The present studies were designed to investigate the signal transduction pathways controlling the expression of MCM6 and MCM7 in VSMC in response to mitogenic stimuli. |
| 2740 | 14516785 | MCM6 and MCM7 expression was substantially increased after stimulation with platelet-derived growth factor-BB and insulin. |
| 2741 | 14516785 | Pretreatment with PD98059, a specific inhibitor of the extracellular signal-regulated kinases (ERK)-mitogen-activated protein kinase (MAPK), competely inhibited the mitogen-induced MCM6 and MCM7 mRNA and protein expression, demonstrating a critical role for this pathway in transmitting transmembrane signals required for the initiation of DNA replication. |
| 2742 | 14516785 | The p38MAPK inhibitor SB203580, the phosphatidylinositol 3 kinase (PI3-kinase) pathway inhibitor wortmannin, and the protein kinase C pathway (PKC) inhibitor Gö 6976 did not significantly affect mitogen-induced MCM6 and MCM7 expression. |
| 2743 | 14516785 | Transient transfection experiments revealed that PD98059 inhibited mitogen-induced MCM6 and MCM7 transcriptional activation. |
| 2744 | 14516785 | Inhibition of mitogen-induced MCM6 and MCM7 expression by PD98059 was reversed by ectopic overexpression of E2F, indicating that ERK/MAPK signaling is required for events that occur upstream of E2F release from phosphorylated Rb. |
| 2745 | 14555183 | Phosphatidylinositol 3-kinase in angiotensin II-induced hypertrophy of vascular smooth muscle cells. |
| 2746 | 14555183 | Angiotensin II time and dose dependently stimulated phosphorylation of 4E-BP1 through the angiotensin AT(1) receptor. |
| 2747 | 14555183 | Pretreatment with wortmannin or 2-(4-Morpholinyl)-8-phenyl-4H-1-benzopyran-4-one (LY294002), a PI 3-kinase inhibitor, suppressed angiotensin II-induced phosphorylation, but a mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinases (ERK) kinase-1 (MEK-1) inhibitor, 2'-Amino-3'-methoxyflavone (PD98059), and a p38 MAPK inhibitor, 4-(4-Fluorophenyl)-2-(4-methylsulfinylphenyl)-5-(4-pyridyl)1H-imidazole (SB203580), had no effect. |
| 2748 | 14555183 | With regard to the involvement of mammalian target of rapamycin (mTOR) and p70 S6 kinase, angiotensin II-induced phosphorylation was abolished by pretreatment with rapamycin, but not by tosylphenylalanine chloromethyl ketone or tosyllysine chloromethyl ketone. |
| 2749 | 14555183 | Thus, angiotensin II induces the phosphorylation of 4E-BP1 via the PI 3-kinase/mTOR pathway, but not via ERK or p70 S6 kinase. |
| 2750 | 14593614 | The two main transduction pathways are the phosphatidylinositol 3 kinase pathway activating protein kinase B which is involved in priority in metabolic effects, and the MAP kinase pathway involved in nuclear effects, proliferation and differentiation. |
| 2751 | 14593614 | This phosphorylation is activated in response to different signals involved in insulin resistance, hyperinsulinism, TNFalpha or increased free fatty acids from adipose tissue, which are transformed inside the cell in acyl-CoA. |
| 2752 | 14596593 | Cellular effects of small molecule PTP1B inhibitors on insulin signaling. |
| 2753 | 14596593 | Protein tyrosine phosphatase 1B (PTP1B) is implicated as a negative regulator of insulin receptor (IR) signaling and a potential drug target for the treatment of type 2 diabetes and other associated metabolic syndromes. |
| 2754 | 14596593 | To further define the role of PTP1B in insulin signaling and to test the hypothesis that blocking the activity of PTP1B would augment the action of insulin, we prepared several cell permeable, potent and selective, small molecule PTP1B inhibitors, and evaluated their biological effects in several insulin sensitive cell lines. |
| 2755 | 14596593 | Our data indicate that PTP1B inhibitors bind to and colocalize with PTP1B on the surface of the endoplasmic reticulum and PTP1B exerts its negative effect on insulin signaling upstream of phosphatidylinositol 3-kinase and MEK1. |
| 2756 | 14596593 | Treatment of cells with PTP1B inhibitors, both in the presence and in the absence of insulin, markedly enhances IRbeta and IRS-1 phosphorylation, Akt and ERK1/2 activation, Glut4 translocation, glucose uptake, and Elk1 transcriptional activation and cell proliferation. |
| 2757 | 14596593 | These results indicate that small molecule inhibitors targeted to PTP1B can act as both insulin mimetics and insulin sensitizers. |
| 2758 | 14596593 | Taken together, our findings combined with results from PTP1B knockout, antisense, and biochemical studies provide strong evidence that PTP1B negatively regulates insulin signaling and that small molecule PTP1B inhibitors have the ability to potentiate and augment the action of insulin. |
| 2759 | 14604996 | Role of insulin receptor substrates and protein kinase C-zeta in vascular permeability factor/vascular endothelial growth factor expression in pancreatic cancer cells. |
| 2760 | 14604996 | Previously we have shown that in AsPC-1 pancreatic adenocarcinoma cells, insulin-like growth factor receptor (IGF-IR) regulates VPF/VEGF expression. |
| 2761 | 14604996 | Insulin receptor substrate-1 and -2 (IRS-1 and IRS-2), two major downstream molecules of IGF-1R, are known to be important in the genesis of diabetes. |
| 2762 | 14604996 | The Sp1-dependent VPF/VEGF transcription is regulated mainly by IRS-2. |
| 2763 | 14604996 | Protein kinase C-zeta (PKC-zeta) plays a central role in VPF/VEGF expression and acts as a switching element. |
| 2764 | 14604996 | Furthermore, we have also demonstrated that the phosphatidylinositol 3-kinase pathway, but not the Ras pathway, is a downstream event of IRS proteins for VPF/VEGF expression in AsPC-1 cells. |
| 2765 | 14604996 | Interestingly, like renal cancer cells, in AsPC-1 cells PKC-zeta leads to direct Sp1-dependent VPF/VEGF transcription; in addition, it also promotes a negative feedback loop to IRS-2 that decreases the association of IRS-2/IGF-1R and IRS-2/p85. |
| 2766 | 14604996 | Taken together, our results show that in AsPC-1 pancreatic carcinoma cells, Sp1-dependent VPF/VEGF transcription is controlled by IGF-1R signaling through IRS-2 proteins and modulated by a negative feedback loop of PKC-zeta to IRS-2. |
| 2767 | 14617576 | Insulin-like growth factor (IGF)-I/IGF-binding protein-3 complex: therapeutic efficacy and mechanism of protection against type 1 diabetes. |
| 2768 | 14617576 | Administration of IGF-I either alone or as an IGF-I/IGFBP-3 complex reduced the severity of insulitis and delayed the onset of T1D in nonobese diabetic mice, but IGF-I/IGFBP-3 was significantly more effective. |
| 2769 | 14617576 | Protection from T1D elicited by IGF-I/IGFBP-3 was mediated by up-regulated CCL4 and down-regulated CCL3 gene expression in pancreatic draining lymph nodes, activation of the phosphatidylinositol 3-kinase and Akt/protein kinase B signaling pathway of beta-cells, reduced beta-cell apoptosis, and stimulation of beta-cell replication. |
| 2770 | 14617576 | Reduced beta-cell apoptosis resulted from elevated Bcl-2 and Bcl-X(L) activity and diminished caspase-9 activity, indicating a novel role for a mitochondrial-dependent pathway of beta-cell death. |
| 2771 | 14617576 | Thus, IGF-I/IGFBP-3 affords more efficient protection from insulitis, beta-cell destruction, and T1D than IGF-I, and this complex may represent an efficacious therapeutic treatment for the prevention of T1D. |
| 2772 | 14623341 | Overexpression of Fer increases the association of tyrosine-phosphorylated IRS-1 with P85 phosphatidylinositol kinase via SH2 domain of Fer in transfected cells. |
| 2773 | 14623341 | We have reported that the protein-tyrosine kinase Fer is associated with signaling complexes containing insulin receptor substrate-1 (IRS-1) and phosphatidylinositol 3-kinase (PI-3 kinase) in insulin-stimulated 3T3-L1 adipocytes [J. |
| 2774 | 14623341 | Based on transfection study, we have demonstrated that overexpression of both Fer and IRS-1 can induce Fer/IRS-1/P85 complexes without insulin stimulation and SH2 domain of Fer is essential for this complex. |
| 2775 | 14623341 | Taken together, these data suggested that Fer may play a critically important role to form Fer/IRS-1/P85 complex in LDM of insulin-stimulated adipocytes and elicit biological effect through PI-3 kinase activity in LDM. |
| 2776 | 14633857 | Activation of vascular endothelial growth factor receptor-1 sustains angiogenesis and Bcl-2 expression via the phosphatidylinositol 3-kinase pathway in endothelial cells. |
| 2777 | 14633857 | Vascular insufficiency and retinal ischemia precede many proliferative retinopathies and stimulate secretion of various vasoactive growth factors, including vascular endothelial growth factor (VEGF) and placenta growth factor (PlGF). |
| 2778 | 14633857 | It is unclear, however, how PlGF, which is elevated in proliferative diabetic retinopathy and is a VEGF homolog that binds only to VEGF receptor (VEGFR)-1, promotes pathological angiogenesis. |
| 2779 | 14633857 | When primary microvascular endothelial cells were grown on collagen gels, PlGF-containing ligands upregulated Bcl-2 expression and stimulated the formation of capillary-like tube networks that were retained for up to 14 days in culture. |
| 2780 | 14633857 | In contrast, VEGF-induced tube formations and Bcl-2 expression were significantly decreased at the end of this period. |
| 2781 | 14633857 | Flow cytometry analysis of annexin-V/propidium iodide-stained cells revealed that PlGF and PlGF/VEGF heterodimer inhibited apoptosis in serum-deprived endothelial cells. |
| 2782 | 14633857 | These two growth factors stimulated a survival signaling pathway phosphatidylinositol 3-kinase (PI3K), as identified by increased Akt phosphorylation and because blocking PI3K signalling by adenovirus-mediated overexpression of wild-type phosphatase and tensin homolog on chromosome 10 (PTEN) disrupted angiogenesis and decreased Bcl-2 expression by PlGF and PlGF/VEGF heterodimer, whereas a dominant-negative PTEN mutant enhanced endothelial sprout formation and Bcl-2 expression. |
| 2783 | 14633857 | Activation of vascular endothelial growth factor receptor-1 sustains angiogenesis and Bcl-2 expression via the phosphatidylinositol 3-kinase pathway in endothelial cells. |
| 2784 | 14633857 | Vascular insufficiency and retinal ischemia precede many proliferative retinopathies and stimulate secretion of various vasoactive growth factors, including vascular endothelial growth factor (VEGF) and placenta growth factor (PlGF). |
| 2785 | 14633857 | It is unclear, however, how PlGF, which is elevated in proliferative diabetic retinopathy and is a VEGF homolog that binds only to VEGF receptor (VEGFR)-1, promotes pathological angiogenesis. |
| 2786 | 14633857 | When primary microvascular endothelial cells were grown on collagen gels, PlGF-containing ligands upregulated Bcl-2 expression and stimulated the formation of capillary-like tube networks that were retained for up to 14 days in culture. |
| 2787 | 14633857 | In contrast, VEGF-induced tube formations and Bcl-2 expression were significantly decreased at the end of this period. |
| 2788 | 14633857 | Flow cytometry analysis of annexin-V/propidium iodide-stained cells revealed that PlGF and PlGF/VEGF heterodimer inhibited apoptosis in serum-deprived endothelial cells. |
| 2789 | 14633857 | These two growth factors stimulated a survival signaling pathway phosphatidylinositol 3-kinase (PI3K), as identified by increased Akt phosphorylation and because blocking PI3K signalling by adenovirus-mediated overexpression of wild-type phosphatase and tensin homolog on chromosome 10 (PTEN) disrupted angiogenesis and decreased Bcl-2 expression by PlGF and PlGF/VEGF heterodimer, whereas a dominant-negative PTEN mutant enhanced endothelial sprout formation and Bcl-2 expression. |
| 2790 | 14638678 | Phosphatidylinositol 3-kinase signaling regulates the expression of several genes involved in lipid and glucose homeostasis; deregulation of these genes may contribute to insulin resistance and progression toward type 2 diabetes. |
| 2791 | 14638678 | By employing RNA arbitrarily primed-PCR to search for novel phosphatidylinositol 3-kinase-regulated genes in response to insulin in isolated rat adipocytes, we identified fatty aldehyde dehydrogenase (FALDH), a key component of the detoxification pathway of aldehydes arising from lipid peroxidation events. |
| 2792 | 14638678 | Upon insulin injection, FALDH mRNA expression increased in rat liver and white adipose tissue and was impaired in two models of insulin-resistant mice, db/db and high fat diet mice. |
| 2793 | 14638678 | FALDH mRNA levels were 4-fold decreased in streptozotocin-treated rats, suggesting that FALDH deregulation occurs both in hyperinsulinemic insulin-resistant state and hypoinsulinemic type 1 diabetes models. |
| 2794 | 14638678 | Moreover, insulin treatment increases FALDH activity in hepatocytes, and expression of FALDH was augmented during adipocyte differentiation. |
| 2795 | 14638678 | Considering the detoxifying role of FALDH, its deregulation in insulin-resistant and type 1 diabetic models may contribute to the lipid-derived oxidative stress. |
| 2796 | 14638678 | Taken together, our observations illustrate the importance of FALDH in insulin action and its deregulation in states associated with altered insulin signaling. |
| 2797 | 14638678 | Phosphatidylinositol 3-kinase signaling regulates the expression of several genes involved in lipid and glucose homeostasis; deregulation of these genes may contribute to insulin resistance and progression toward type 2 diabetes. |
| 2798 | 14638678 | By employing RNA arbitrarily primed-PCR to search for novel phosphatidylinositol 3-kinase-regulated genes in response to insulin in isolated rat adipocytes, we identified fatty aldehyde dehydrogenase (FALDH), a key component of the detoxification pathway of aldehydes arising from lipid peroxidation events. |
| 2799 | 14638678 | Upon insulin injection, FALDH mRNA expression increased in rat liver and white adipose tissue and was impaired in two models of insulin-resistant mice, db/db and high fat diet mice. |
| 2800 | 14638678 | FALDH mRNA levels were 4-fold decreased in streptozotocin-treated rats, suggesting that FALDH deregulation occurs both in hyperinsulinemic insulin-resistant state and hypoinsulinemic type 1 diabetes models. |
| 2801 | 14638678 | Moreover, insulin treatment increases FALDH activity in hepatocytes, and expression of FALDH was augmented during adipocyte differentiation. |
| 2802 | 14638678 | Considering the detoxifying role of FALDH, its deregulation in insulin-resistant and type 1 diabetic models may contribute to the lipid-derived oxidative stress. |
| 2803 | 14638678 | Taken together, our observations illustrate the importance of FALDH in insulin action and its deregulation in states associated with altered insulin signaling. |
| 2804 | 14641043 | Down-regulation of insulin receptor tyrosine phosphorylation and subsequent steps in the insulin signalling pathway, including insulin receptor substrate-1 (IRS-1)-associated phosphoinositide 3-kinase (PI3K), Akt kinase serine phosphorylation and activity and glucose transporter (GLUT-4) protein content, are evident in skeletal muscle after eccentric exercise. |
| 2805 | 14641043 | Furthermore, increased tumour necrosis factor alpha (TNF-alpha) secretion from monocytes is associated with the decrease in PI3K activity after this type of exercise. |
| 2806 | 14641043 | Recent studies have shown that TNF-alpha can increase IRS-1 serine/threonine phosphorylation, which impairs IRS-1 docking to the insulin receptor, and this inhibits insulin signalling. |
| 2807 | 14641043 | Thus a unifying hypothesis to explain insulin resistance after eccentric exercise may include inflammation arising from the disruption of muscle-cell integrity, leading to an acute-phase response that includes TNF-alpha, with the latter inhibiting insulin signalling and subsequent metabolic events. |
| 2808 | 14641043 | In contrast, exercise training increases insulin signalling and GLUT-4 expression, decreases TNF-alpha expression in skeletal muscle, and is associated with enhanced insulin sensitivity. |
| 2809 | 14641043 | Down-regulation of insulin receptor tyrosine phosphorylation and subsequent steps in the insulin signalling pathway, including insulin receptor substrate-1 (IRS-1)-associated phosphoinositide 3-kinase (PI3K), Akt kinase serine phosphorylation and activity and glucose transporter (GLUT-4) protein content, are evident in skeletal muscle after eccentric exercise. |
| 2810 | 14641043 | Furthermore, increased tumour necrosis factor alpha (TNF-alpha) secretion from monocytes is associated with the decrease in PI3K activity after this type of exercise. |
| 2811 | 14641043 | Recent studies have shown that TNF-alpha can increase IRS-1 serine/threonine phosphorylation, which impairs IRS-1 docking to the insulin receptor, and this inhibits insulin signalling. |
| 2812 | 14641043 | Thus a unifying hypothesis to explain insulin resistance after eccentric exercise may include inflammation arising from the disruption of muscle-cell integrity, leading to an acute-phase response that includes TNF-alpha, with the latter inhibiting insulin signalling and subsequent metabolic events. |
| 2813 | 14641043 | In contrast, exercise training increases insulin signalling and GLUT-4 expression, decreases TNF-alpha expression in skeletal muscle, and is associated with enhanced insulin sensitivity. |
| 2814 | 14643059 | Here, we review the mechanisms by which leptin activates intracellular signaling and the roles of two specific leptin-activated signals [phosphatidylinositol 3-kinase and signal transducer and activator of transcription-3 (STAT3)] in the regulation of body weight and neuroendocrine function. |
| 2815 | 14643059 | The pathway by which leptin activates STAT3 is particularly intriguing because it is crucial for the regulation of feeding but dispensable for the control of reproductive and growth axes. |
| 2816 | 14645111 | Calcium-sensing receptor induces proliferation through p38 mitogen-activated protein kinase and phosphatidylinositol 3-kinase but not extracellularly regulated kinase in a model of humoral hypercalcemia of malignancy. |
| 2817 | 14645111 | Using H-500 rat Leydig cancer cells as a model of humoral hypercalcemia of malignancy (HHM), we previously showed that high Ca(2+) induces PTH-related peptide (PTHrP) secretion via the calcium-sensing receptor (CaR) and mitogen- and stress-activated kinases, e.g. |
| 2818 | 14645111 | MAPK kinase 1 (MEK1), p38 MAPK, and stress-activated protein kinase 1/c-Jun N-terminal kinase. |
| 2819 | 14645111 | Inhibition of phosphatidylinositol 3-kinase (PI3K) and p38 MAPK but not MEK1 abolished the mitogenic effect. |
| 2820 | 14645111 | Activation of PI3K by elevated Ca(2+) was documented by phosphorylation of its downstream kinase, protein kinase B. |
| 2821 | 14645111 | Taken together, our data show that activation of PI3K and p38 MAPK but not of MEK1/ERK by the CaR promotes proliferation of H-500 cells as well as affords protection against apoptosis. |
| 2822 | 14645111 | Calcium-sensing receptor induces proliferation through p38 mitogen-activated protein kinase and phosphatidylinositol 3-kinase but not extracellularly regulated kinase in a model of humoral hypercalcemia of malignancy. |
| 2823 | 14645111 | Using H-500 rat Leydig cancer cells as a model of humoral hypercalcemia of malignancy (HHM), we previously showed that high Ca(2+) induces PTH-related peptide (PTHrP) secretion via the calcium-sensing receptor (CaR) and mitogen- and stress-activated kinases, e.g. |
| 2824 | 14645111 | MAPK kinase 1 (MEK1), p38 MAPK, and stress-activated protein kinase 1/c-Jun N-terminal kinase. |
| 2825 | 14645111 | Inhibition of phosphatidylinositol 3-kinase (PI3K) and p38 MAPK but not MEK1 abolished the mitogenic effect. |
| 2826 | 14645111 | Activation of PI3K by elevated Ca(2+) was documented by phosphorylation of its downstream kinase, protein kinase B. |
| 2827 | 14645111 | Taken together, our data show that activation of PI3K and p38 MAPK but not of MEK1/ERK by the CaR promotes proliferation of H-500 cells as well as affords protection against apoptosis. |
| 2828 | 14645111 | Calcium-sensing receptor induces proliferation through p38 mitogen-activated protein kinase and phosphatidylinositol 3-kinase but not extracellularly regulated kinase in a model of humoral hypercalcemia of malignancy. |
| 2829 | 14645111 | Using H-500 rat Leydig cancer cells as a model of humoral hypercalcemia of malignancy (HHM), we previously showed that high Ca(2+) induces PTH-related peptide (PTHrP) secretion via the calcium-sensing receptor (CaR) and mitogen- and stress-activated kinases, e.g. |
| 2830 | 14645111 | MAPK kinase 1 (MEK1), p38 MAPK, and stress-activated protein kinase 1/c-Jun N-terminal kinase. |
| 2831 | 14645111 | Inhibition of phosphatidylinositol 3-kinase (PI3K) and p38 MAPK but not MEK1 abolished the mitogenic effect. |
| 2832 | 14645111 | Activation of PI3K by elevated Ca(2+) was documented by phosphorylation of its downstream kinase, protein kinase B. |
| 2833 | 14645111 | Taken together, our data show that activation of PI3K and p38 MAPK but not of MEK1/ERK by the CaR promotes proliferation of H-500 cells as well as affords protection against apoptosis. |
| 2834 | 14645111 | Calcium-sensing receptor induces proliferation through p38 mitogen-activated protein kinase and phosphatidylinositol 3-kinase but not extracellularly regulated kinase in a model of humoral hypercalcemia of malignancy. |
| 2835 | 14645111 | Using H-500 rat Leydig cancer cells as a model of humoral hypercalcemia of malignancy (HHM), we previously showed that high Ca(2+) induces PTH-related peptide (PTHrP) secretion via the calcium-sensing receptor (CaR) and mitogen- and stress-activated kinases, e.g. |
| 2836 | 14645111 | MAPK kinase 1 (MEK1), p38 MAPK, and stress-activated protein kinase 1/c-Jun N-terminal kinase. |
| 2837 | 14645111 | Inhibition of phosphatidylinositol 3-kinase (PI3K) and p38 MAPK but not MEK1 abolished the mitogenic effect. |
| 2838 | 14645111 | Activation of PI3K by elevated Ca(2+) was documented by phosphorylation of its downstream kinase, protein kinase B. |
| 2839 | 14645111 | Taken together, our data show that activation of PI3K and p38 MAPK but not of MEK1/ERK by the CaR promotes proliferation of H-500 cells as well as affords protection against apoptosis. |
| 2840 | 14647049 | Impaired IRS-1/PI3-kinase signaling in patients with HCV: a mechanism for increased prevalence of type 2 diabetes. |
| 2841 | 14647049 | In contrast, insulin-stimulated IRS-1 tyrosine phosphorylation was decreased by 2-fold in HCV-infected subjects compared with non-HCV-infected subjects (P <.05). |
| 2842 | 14647049 | The observed reductions in IRS-1 tyrosine phosphorylation were accompanied by a 3.4-fold decrease in IRS-1/p85 phosphatidylinositol 3-kinase (PI3-kinase) association and a 2.5-fold decrease in IRS-1-associated PI3-kinase enzymatic activity (P <.05 vs. non-HCV). |
| 2843 | 14647049 | This was accompanied by a marked reduction in insulin-stimulated Akt phosphorylation without any alterations in mitogen-activated protein kinase (MAPK) phosphorylation. |
| 2844 | 14647049 | Cellular contents of the hepatic p85 subunit of PI3-kinase were comparable between HCV-infected and non-HCV-infected subjects. |
| 2845 | 14647049 | HCV infection leads to a postreceptor defect in IRS-1 association with the IR and (2). insulin signaling defects in hepatic IRS-1 tyrosine phosphorylation and PI3-kinase association/activation may contribute to insulin resistance, which leads to the development of type 2 diabetes mellitus in patients with HCV infection. |
| 2846 | 14683460 | Phosphatidyl Inositol 3-Kinase (PI3K) is central to mediating insulin-s metabolic effects. |
| 2847 | 14683460 | Inhibition of PI3K activity results in a blockade of insulin signaling including glucose uptake and glyocogen synthesis. |
| 2848 | 14683460 | Mice lacking one of these enzymes, Src-Homology Inositol Phosphatase-2 (SHIP2), demonstrate increased insulin sensitivity, suggesting that pharmacological inhibition of SHIP2 could alleviate insulin resistance. |
| 2849 | 14683460 | Recent studies demonstrate elevated SHIP2 expression is associated with insulin resistance in human patients. |
| 2850 | 14683460 | Comparing the studies on SHIP2 and other phosphatases suggests how inhibition of SHIP2 leads to increased insulin sensitivity without deleterious effects. |
| 2851 | 14683460 | This review focuses on the emergence of SHIP2 as a target in the insulin-signaling pathway for the treatment of type 2 diabetes. |
| 2852 | 14683460 | Phosphatidyl Inositol 3-Kinase (PI3K) is central to mediating insulin-s metabolic effects. |
| 2853 | 14683460 | Inhibition of PI3K activity results in a blockade of insulin signaling including glucose uptake and glyocogen synthesis. |
| 2854 | 14683460 | Mice lacking one of these enzymes, Src-Homology Inositol Phosphatase-2 (SHIP2), demonstrate increased insulin sensitivity, suggesting that pharmacological inhibition of SHIP2 could alleviate insulin resistance. |
| 2855 | 14683460 | Recent studies demonstrate elevated SHIP2 expression is associated with insulin resistance in human patients. |
| 2856 | 14683460 | Comparing the studies on SHIP2 and other phosphatases suggests how inhibition of SHIP2 leads to increased insulin sensitivity without deleterious effects. |
| 2857 | 14683460 | This review focuses on the emergence of SHIP2 as a target in the insulin-signaling pathway for the treatment of type 2 diabetes. |
| 2858 | 14702115 | Since cytokines or insulin resistance are common in catabolic states and will activate caspases, we examined whether caspase-3 would break down actomyosin. |
| 2859 | 14702115 | Serum deprivation of L6 muscle cells stimulates actin cleavage and proteolysis; insulin blocks these responses by a mechanism requiring PI3K. |
| 2860 | 14704736 | Glucose transport (GLUT4), phosphorylation (hexokinase) and storage (glycogen synthase) are the three potential rate-controlling steps regulating insulin-stimulated muscle glucose metabolism, and all three have been implicated as being the major defects responsible for causing insulin resistance in patients with type 2 diabetes. |
| 2861 | 14704736 | Using a similar (13)C/(31)P MRS approach, we have also demonstrated that fatty acids cause insulin resistance in humans due to a decrease in insulin-stimulated muscle glucose transport activity, which could be attributed to reduced insulin-stimulated IRS-1-associated phosphatidylinositol 3-kinase activity, a required step in insulin-stimulated glucose transport into muscle. |
| 2862 | 14704736 | Furthermore, we have recently proposed that this defect in insulin-stimulated muscle glucose transport activity may be due to the activation of a serine kinase cascade involving protein kinase C theta and IKK-beta, which are key downstream mediators of tissue inflammation. |
| 2863 | 14704736 | Finally, we propose that any perturbation that leads to an increase in intramyocellular lipid (fatty acid metabolites) content such as acquired or inherited defects in mitochondrial fatty acid oxidation, defects in adipocyte fat metabolism or simply increased fat delivery to muscle/liver due to increased energy intake will lead to insulin resistance through this final common pathway. |
| 2864 | 14749507 | LRb initiates signaling via three major mechanisms: 1) Tyr(985) of LRb recruits SH2-containing tyrosine phosphatase (SHP-2); 2) Tyr(1138) of LRb recruits signal transducer and activator of transcription 3 (STAT3); and 3) tyrosine phosphorylation sites on the receptor-associated Jak2 likely recruit numerous undefined signaling proteins. |
| 2865 | 14749507 | The Tyr(985) --> SHP-2 pathway is a major regulator of extracellular signal-regulated kinase (ERK) activation during leptin signaling in cultured cells, while the Tyr(1138) --> STAT3 pathway induces the feedback inhibitor, suppressor of cytokine signaling 3 (SOCS3), as well as important positive effectors of leptin action. |
| 2866 | 14749507 | The Jak2-dependent activation of the insulin receptor substrate (IRS) protein --> phosphatidylinositol 3-kinase (PI3'-K) pathway appears to regulate membrane potential in LRb-expressing neurons and contributes to the regulation of feeding. |
| 2867 | 14749507 | Interestingly, the Tyr(1138) --> STAT3 pathway does not strongly regulate neuropeptide Y (NPY) and thus is not required for the control of reproduction and growth. |
| 2868 | 14769918 | Liver-specific deletion of negative regulator Pten results in fatty liver and insulin hypersensitivity [corrected]. |
| 2869 | 14769918 | In the liver, insulin controls both lipid and glucose metabolism through its cell surface receptor and intracellular mediators such as phosphatidylinositol 3-kinase and serine-threonine kinase AKT. |
| 2870 | 14769918 | Here, we investigated the function of phosphatase and tension homologue deleted on chromosome 10 (PTEN), a negative regulator of the phosphatidylinositol 3-kinase/AKT pathway, by targeted deletion of Pten in murine liver. |
| 2871 | 14769918 | Interestingly, Pten liver-specific deletion causes enhanced liver insulin action with improved systemic glucose tolerance. |
| 2872 | 14769918 | Thus, deletion of Pten in the liver may provide a valuable model that permits the study of the metabolic actions of insulin signaling in the liver, and PTEN may be a promising target for therapeutic intervention for type 2 diabetes. |
| 2873 | 14769918 | Liver-specific deletion of negative regulator Pten results in fatty liver and insulin hypersensitivity [corrected]. |
| 2874 | 14769918 | In the liver, insulin controls both lipid and glucose metabolism through its cell surface receptor and intracellular mediators such as phosphatidylinositol 3-kinase and serine-threonine kinase AKT. |
| 2875 | 14769918 | Here, we investigated the function of phosphatase and tension homologue deleted on chromosome 10 (PTEN), a negative regulator of the phosphatidylinositol 3-kinase/AKT pathway, by targeted deletion of Pten in murine liver. |
| 2876 | 14769918 | Interestingly, Pten liver-specific deletion causes enhanced liver insulin action with improved systemic glucose tolerance. |
| 2877 | 14769918 | Thus, deletion of Pten in the liver may provide a valuable model that permits the study of the metabolic actions of insulin signaling in the liver, and PTEN may be a promising target for therapeutic intervention for type 2 diabetes. |
| 2878 | 15016802 | The pro-hypertrophic basic helix-loop-helix protein p8 is degraded by the ubiquitin/proteasome system in a protein kinase B/Akt- and glycogen synthase kinase-3-dependent manner, whereas endothelin induction of p8 mRNA and renal mesangial cell hypertrophy require NFAT4. |
| 2879 | 15016802 | This degradation is mediated by phosphatidylinositol 3-kinase and protein kinase B/Akt. |
| 2880 | 15028732 | Both insulin signaling defects in the liver and obesity contribute to insulin resistance and cause diabetes in Irs2(-/-) mice. |
| 2881 | 15028732 | Irs2(-/-) mice also exhibit obesity and hyperleptinemia associated with impairment of hypothalamic phosphatidylinositol 3-kinase activation. |
| 2882 | 15028732 | Continuous intracerebroventricular leptin infusion or caloric restriction yielded Irs2(-/-) mice whose adiposity was comparable to that of Irs2(+/+) mice, and both the hyperglycemia and the hyperinsulinemia of these mice improved with increased Rd albeit partially. |
| 2883 | 15028732 | Finally combination treatment consisting of adenovirus-mediated gene transfer of IRS-2 and continuous intracerebroventricular leptin infusion completely reversed the hyperglycemia and hyperinsulinemia in Irs2(-/-) mice. |
| 2884 | 15028732 | We therefore concluded that a combination of increased EGP due to insulin signaling defects in the liver and reduced Rd due to obesity accounts for the systemic insulin resistance in Irs2(-/-) mice. |
| 2885 | 15037619 | TDAG51 mediates the effects of insulin-like growth factor I (IGF-I) on cell survival. |
| 2886 | 15037619 | Insulin-like growth factor-I (IGF-I) receptors and insulin receptors belong to the same subfamily of receptor tyrosine kinases and share a similar set of intracellular signaling pathways, despite their distinct biological actions. |
| 2887 | 15037619 | In the present study, we evaluated T cell death-associated gene 51 (TDAG51), which we previously identified by cDNA microarray analysis as a gene specifically induced by IGF-I. |
| 2888 | 15037619 | We characterized the signaling pathways by which IGF-I induces TDAG51 gene expression and the functional role of TDAG51 in IGF-I signaling in NIH-3T3 (NWTb3) cells, which overexpress the human IGF-I receptor. |
| 2889 | 15037619 | Treatment with IGF-I increased TDAG51 mRNA and protein levels in NWTb3 cells. |
| 2890 | 15037619 | This effect of IGF-I was specifically mediated by the IGF-IR, because IGF-I did not induce TDAG51 expression in NIH-3T3 cells overexpressing a dominant-negative IGF-I receptor. |
| 2891 | 15037619 | Through the use of specific inhibitors of various protein kinases, we found that IGF-I induced TDAG51 expression via the p38 MAPK pathway. |
| 2892 | 15037619 | The ERK, JNK, and phosphatidylinositol 3-kinase pathways were not involved in IGF-I-induced regulation of TDAG51. |
| 2893 | 15037619 | To assess the role of TDAG51 in IGF-I signaling, we used small interfering RNA (siRNA) expression vectors directed at two different target sites to reduce the level of TDAG51 protein. |
| 2894 | 15037619 | Furthermore, TDAG51 siRNA expression abolished the ability of IGF-I to rescue cells from serum starvation-induced apoptosis. |
| 2895 | 15037619 | These findings suggest that TDAG51 plays an important role in the anti-apoptotic effects of IGF-I. |
| 2896 | 15050532 | Stimulatory effect of IGF-I and VEGF on eNOS message, protein expression, eNOS phosphorylation and nitric oxide production in rat glomeruli, and the involvement of PI3-K signaling pathway. |
| 2897 | 15050532 | We set out to determine whether IGF-I and/or VEGF165 directly stimulate NO production in rat glomeruli and whether the expression of NO synthase (NOS) isoforms as well as eNOS phosphorylation contribute to NO generation by IGF-I and VEGF. |
| 2898 | 15050532 | Long-term exposure to IGF-I and/or VEGF165 augments NO production through increased eNOS mRNA, protein expression and phosphatidylinositol 3-kinase (PI3-K) signaling pathway plays a major role in this process; short-term exposure to IGF-I and/or VEGF(165) activates eNOS activity via phosphorylation by a PI3-K/Akt dependent pathway. |
| 2899 | 15050532 | Our data suggest the great possibility that increased endogenous IGF-I and VEGF may be responsible for the up-regulation of eNOS expression and NO production which contributes to glomerular hyperfiltration in early diabetic kidneys. |
| 2900 | 15050532 | IGF-I is a newly described growth factor that up-regulates eNOS expression and PI3-K plays a major role in this process. |
| 2901 | 15050532 | Stimulatory effect of IGF-I and VEGF on eNOS message, protein expression, eNOS phosphorylation and nitric oxide production in rat glomeruli, and the involvement of PI3-K signaling pathway. |
| 2902 | 15050532 | We set out to determine whether IGF-I and/or VEGF165 directly stimulate NO production in rat glomeruli and whether the expression of NO synthase (NOS) isoforms as well as eNOS phosphorylation contribute to NO generation by IGF-I and VEGF. |
| 2903 | 15050532 | Long-term exposure to IGF-I and/or VEGF165 augments NO production through increased eNOS mRNA, protein expression and phosphatidylinositol 3-kinase (PI3-K) signaling pathway plays a major role in this process; short-term exposure to IGF-I and/or VEGF(165) activates eNOS activity via phosphorylation by a PI3-K/Akt dependent pathway. |
| 2904 | 15050532 | Our data suggest the great possibility that increased endogenous IGF-I and VEGF may be responsible for the up-regulation of eNOS expression and NO production which contributes to glomerular hyperfiltration in early diabetic kidneys. |
| 2905 | 15050532 | IGF-I is a newly described growth factor that up-regulates eNOS expression and PI3-K plays a major role in this process. |
| 2906 | 15050532 | Stimulatory effect of IGF-I and VEGF on eNOS message, protein expression, eNOS phosphorylation and nitric oxide production in rat glomeruli, and the involvement of PI3-K signaling pathway. |
| 2907 | 15050532 | We set out to determine whether IGF-I and/or VEGF165 directly stimulate NO production in rat glomeruli and whether the expression of NO synthase (NOS) isoforms as well as eNOS phosphorylation contribute to NO generation by IGF-I and VEGF. |
| 2908 | 15050532 | Long-term exposure to IGF-I and/or VEGF165 augments NO production through increased eNOS mRNA, protein expression and phosphatidylinositol 3-kinase (PI3-K) signaling pathway plays a major role in this process; short-term exposure to IGF-I and/or VEGF(165) activates eNOS activity via phosphorylation by a PI3-K/Akt dependent pathway. |
| 2909 | 15050532 | Our data suggest the great possibility that increased endogenous IGF-I and VEGF may be responsible for the up-regulation of eNOS expression and NO production which contributes to glomerular hyperfiltration in early diabetic kidneys. |
| 2910 | 15050532 | IGF-I is a newly described growth factor that up-regulates eNOS expression and PI3-K plays a major role in this process. |
| 2911 | 15059962 | Mechanistically, Galpha9 functions rapidly following receptor stimulation to negatively regulate PI3K/PTEN, adenylyl cyclase, and guanylyl cyclase pathways. |
| 2912 | 15064952 | Insulin-mediated stimulation of the L-arginine/NO pathway is thus associated with increased hCAT-1 and hCAT-2B mRNA, and eNOS expression, via mechanisms involving membrane hyperpolarization, mitogen-activated protein kinases p42 and p44, phosphatidylinositol 3-kinase, NO and protein kinase C. |
| 2913 | 15069067 | Insulin-induced activation of atypical protein kinase C, but not protein kinase B, is maintained in diabetic (ob/ob and Goto-Kakazaki) liver. |
| 2914 | 15069067 | To understand the mechanisms for these seemingly paradoxical defects, we examined the activation of atypical protein kinase C (aPKC) and protein kinase B (PKB), two key signaling factors that operate downstream of phosphatidylinositol 3-kinase and regulate various insulin-sensitive metabolic processes. |
| 2915 | 15069067 | These findings suggest that, at least in these rodent models, (a) defects in aPKC activation contribute importantly to skeletal muscle insulin resistance observed in both high fat feeding and type 2 diabetes; (b) insulin signaling defects in muscle are not necessarily accompanied by similar defects in liver; (c) defects in hepatic PKB activation occur in association with, and probably contribute importantly to, the development of overt diabetes; and (d) maintenance of hepatic aPKC activation may explain the continued effectiveness of insulin for stimulating certain metabolic actions in the liver. |
| 2916 | 15072967 | There are increasing data suggesting that ANG II acting through its ANG type 1 receptor inhibits the actions of Ins in vascular and skeletal muscle tissue, in part, by interfering with Ins signally through phosphatidylinositol 3-kinase (PI3K) and its downstream protein kinase B (Akt) signaling pathways. |
| 2917 | 15072967 | Activated RhoA and increased reactive oxygen species inhibition of PI3K/Akt signaling results in decreased endothelial cell production of nitric oxide, increased myosin light chain activation with vasoconstriction, and reduced skeletal muscle glucose transport. |
| 2918 | 15072967 | There are increasing data suggesting that ANG II acting through its ANG type 1 receptor inhibits the actions of Ins in vascular and skeletal muscle tissue, in part, by interfering with Ins signally through phosphatidylinositol 3-kinase (PI3K) and its downstream protein kinase B (Akt) signaling pathways. |
| 2919 | 15072967 | Activated RhoA and increased reactive oxygen species inhibition of PI3K/Akt signaling results in decreased endothelial cell production of nitric oxide, increased myosin light chain activation with vasoconstriction, and reduced skeletal muscle glucose transport. |
| 2920 | 15094073 | Leptin and melanocortins, peptides that down regulate food intake and are largely affected by nutrients, are highly interactive with insulin in the CNS probably via the neurotransmitter serotonin. |
| 2921 | 15094073 | In the hypothalamus, insulin and leptin share a common signaling pathway involved in food intake, namely the insulin receptor substrate, phosphatidylinositol 3-kinase pathway. |
| 2922 | 15122091 | Alteration in insulin action: role of IRS-1 serine phosphorylation in the retroregulation of insulin signalling. |
| 2923 | 15122091 | Tyrosine phosphorylation of insulin receptor substrate 1 (IRS-1) and its binding to phosphatidylinositol 3-kinase (PI 3-kinase) are critical events in the insulin signalling cascade leading to insulin-stimulated glucose transport. |
| 2924 | 15122091 | Recent findings demonstrate that "diabetogenic" factors such as FFA, TNFalpha, hyperinsulinemia and cellular stress, increase the serine phosphorylation of IRS-1 and identified Ser307/612/632 as phosphorylated sites. |
| 2925 | 15122091 | These exciting results suggest that serine phosphorylation of IRS-1 is a possible hallmark of insulin resistance in biologically insulin responsive cells or tIssues. |
| 2926 | 15123681 | Insulin receptor substrate-2-dependent interleukin-4 signaling in macrophages is impaired in two models of type 2 diabetes mellitus. |
| 2927 | 15123681 | We have shown previously that hyperinsulinemia inhibits interferon-alpha-dependent activation of phosphatidylinositol 3-kinase (PI3-kinase) through mammalian target of rapamycin (mTOR)-induced serine phosphorylation of insulin receptor substrate (IRS)-1. |
| 2928 | 15123681 | Here we report that chronic insulin and high glucose synergistically inhibit interleukin (IL)-4-dependent activation of PI3-kinase in macrophages via the mTOR pathway. |
| 2929 | 15123681 | Resident peritoneal macrophages (PerMPhis) from diabetic (db/db) mice showed a 44% reduction in IRS-2-associated PI3-kinase activity stimulated by IL-4 compared with PerMPhis from heterozygote (db/+) control mice. |
| 2930 | 15123681 | To investigate the mechanism of this PI3-kinase inhibition, 12-O-tetradecanoylphorbol-13-acetate-matured U937 cells were treated chronically with insulin (1 nm, 18 h) and high glucose (4.5 g/liter, 48 h). |
| 2931 | 15123681 | In these cells, IL-4-stimulated IRS-2-associated PI3-kinase activity was reduced by 37.5%. |
| 2932 | 15123681 | Importantly, chronic insulin or high glucose alone did not impact IL-4-activated IRS-2-associated PI3-kinase. |
| 2933 | 15123681 | Chronic insulin + high glucose did reduce IL-4-dependent IRS-2 tyrosine phosphorylation and p85 association by 54 and 37%, respectively, but did not effect IL-4-activated JAK/STAT signaling. |
| 2934 | 15123681 | When IRS-2 Ser/Thr-Pro motif phosphorylation was examined, chronic insulin + high glucose resulted in a 92% increase in IRS-2 Ser/Thr-Pro motif phosphorylation without a change in IRS-2 mass. |
| 2935 | 15123681 | Pretreatment of matured U937 cells with rapamycin blocked chronic insulin + high glucose-dependent IRS-2 Ser/Thr-Pro motif phosphorylation and restored IL-4-dependent IRS-2-associated PI3-kinase activity. |
| 2936 | 15123681 | Taken together these results indicate that IRS-2-dependent IL-4 signaling in macrophages is impaired in models of type 2 diabetes mellitus through a mechanism that relies on insulin/glucose-dependent Ser/Thr-Pro motif serine phosphorylation mediated by the mTOR pathway. |
| 2937 | 15126243 | LIP in CON reduced insulin-stimulated glucose disposal (Rd) by 25%, insulin-stimulated insulin receptor tyrosine phosphorylation by 17%, phosphatidylinositol 3-kinase activity associated with insulin receptor substrate-1 by 20%, and insulin-stimulated glycogen synthase fractional velocity over baseline (44 vs. 15%; all P < 0.05). |
| 2938 | 15127200 | Oxidative stress induces insulin resistance by activating the nuclear factor-kappa B pathway and disrupting normal subcellular distribution of phosphatidylinositol 3-kinase. |
| 2939 | 15153564 | Regulation of muscle protein degradation: coordinated control of apoptotic and ubiquitin-proteasome systems by phosphatidylinositol 3 kinase. |
| 2940 | 15153564 | As expected, phosphatidylinositol 3 kinase activity (PI3K) was suppressed in muscle; in addition to decreased insulin, the mechanism includes IRS-1 phosphorylation at serine-307. |
| 2941 | 15153564 | Caspase-3 activity was also increased, and the authors linked it to a low PI3K-induced activation of the apoptotic system that includes a conformational change in Bax and release of cytochrome C. |
| 2942 | 15153564 | Atrogin-1/MAFbx expression increased when the authors suppressed PI3K activity in muscle cells. |
| 2943 | 15153564 | The forkhead transcriptional factor, a downstream substrate of PI3K, stimulated atrogin-1/MAFbx promoter transcriptional activity markedly. |
| 2944 | 15153564 | Regulation of muscle protein degradation: coordinated control of apoptotic and ubiquitin-proteasome systems by phosphatidylinositol 3 kinase. |
| 2945 | 15153564 | As expected, phosphatidylinositol 3 kinase activity (PI3K) was suppressed in muscle; in addition to decreased insulin, the mechanism includes IRS-1 phosphorylation at serine-307. |
| 2946 | 15153564 | Caspase-3 activity was also increased, and the authors linked it to a low PI3K-induced activation of the apoptotic system that includes a conformational change in Bax and release of cytochrome C. |
| 2947 | 15153564 | Atrogin-1/MAFbx expression increased when the authors suppressed PI3K activity in muscle cells. |
| 2948 | 15153564 | The forkhead transcriptional factor, a downstream substrate of PI3K, stimulated atrogin-1/MAFbx promoter transcriptional activity markedly. |
| 2949 | 15153564 | Regulation of muscle protein degradation: coordinated control of apoptotic and ubiquitin-proteasome systems by phosphatidylinositol 3 kinase. |
| 2950 | 15153564 | As expected, phosphatidylinositol 3 kinase activity (PI3K) was suppressed in muscle; in addition to decreased insulin, the mechanism includes IRS-1 phosphorylation at serine-307. |
| 2951 | 15153564 | Caspase-3 activity was also increased, and the authors linked it to a low PI3K-induced activation of the apoptotic system that includes a conformational change in Bax and release of cytochrome C. |
| 2952 | 15153564 | Atrogin-1/MAFbx expression increased when the authors suppressed PI3K activity in muscle cells. |
| 2953 | 15153564 | The forkhead transcriptional factor, a downstream substrate of PI3K, stimulated atrogin-1/MAFbx promoter transcriptional activity markedly. |
| 2954 | 15153564 | Regulation of muscle protein degradation: coordinated control of apoptotic and ubiquitin-proteasome systems by phosphatidylinositol 3 kinase. |
| 2955 | 15153564 | As expected, phosphatidylinositol 3 kinase activity (PI3K) was suppressed in muscle; in addition to decreased insulin, the mechanism includes IRS-1 phosphorylation at serine-307. |
| 2956 | 15153564 | Caspase-3 activity was also increased, and the authors linked it to a low PI3K-induced activation of the apoptotic system that includes a conformational change in Bax and release of cytochrome C. |
| 2957 | 15153564 | Atrogin-1/MAFbx expression increased when the authors suppressed PI3K activity in muscle cells. |
| 2958 | 15153564 | The forkhead transcriptional factor, a downstream substrate of PI3K, stimulated atrogin-1/MAFbx promoter transcriptional activity markedly. |
| 2959 | 15153564 | Regulation of muscle protein degradation: coordinated control of apoptotic and ubiquitin-proteasome systems by phosphatidylinositol 3 kinase. |
| 2960 | 15153564 | As expected, phosphatidylinositol 3 kinase activity (PI3K) was suppressed in muscle; in addition to decreased insulin, the mechanism includes IRS-1 phosphorylation at serine-307. |
| 2961 | 15153564 | Caspase-3 activity was also increased, and the authors linked it to a low PI3K-induced activation of the apoptotic system that includes a conformational change in Bax and release of cytochrome C. |
| 2962 | 15153564 | Atrogin-1/MAFbx expression increased when the authors suppressed PI3K activity in muscle cells. |
| 2963 | 15153564 | The forkhead transcriptional factor, a downstream substrate of PI3K, stimulated atrogin-1/MAFbx promoter transcriptional activity markedly. |
| 2964 | 15161747 | Mice that lack acyl CoA:diacylglycerol acyltransferase 1 (DGAT1), a key enzyme in mammalian triglyceride synthesis, have decreased adiposity and increased insulin sensitivity. |
| 2965 | 15161747 | Here we show that insulin-stimulated glucose transport is increased in the skeletal muscle and white adipose tissue (WAT) of chow-fed DGAT1-deficient mice. |
| 2966 | 15161747 | This increase in glucose transport correlated with enhanced insulin-stimulated activities of phosphatidylinositol 3-kinase, protein kinase B (or Akt), and protein kinase Clambda (PKC-lambda), three key molecules in the insulin-signaling pathway, and was associated with decreased levels of serine-phosphorylated insulin receptor substrate 1 (IRS-1), a molecule implicated in insulin resistance. |
| 2967 | 15161747 | Similar findings in insulin signaling were also observed in DGAT1-deficient mice fed a high-fat diet. |
| 2968 | 15161747 | Interestingly, the increased PKC-lambda activity and decreased serine phosphorylation of IRS-1 were observed in chow-fed wild-type mice transplanted with DGAT1-deficient WAT, consistent with our previous finding that transplantation of DGAT1-deficient WAT enhances glucose disposal in wild-type recipient mice. |
| 2969 | 15161747 | Our findings demonstrate that DGAT1 deficiency enhances insulin signaling in the skeletal muscle and WAT, in part through altered expression of adipocyte-derived factors that modulate insulin signaling in peripheral tissues. |
| 2970 | 15181014 | Suppressor of cytokine signaling 3 is a physiological regulator of adipocyte insulin signaling. |
| 2971 | 15181014 | We observed that several cytokines and hormones that induce insulin resistance also stimulate SOCS3 expression in 3T3-L1 adipocytes and that SOCS3 mRNA is increased in adipose tissue of obese/diabetic mice. |
| 2972 | 15181014 | We then hypothesized that SOCS3 may mediate cytokine- and hormone-induced insulin resistance. |
| 2973 | 15181014 | By using SOCS3-deficient adipocytes differentiated from mouse embryonic fibroblasts, we found that SOCS3 deficiency increases insulin-stimulated IRS1 and IRS2 phosphorylation, IRS-associated phosphatidylinositol 3-kinase activity, and insulin-stimulated glucose uptake. |
| 2974 | 15181014 | Moreover, lack of SOCS3 substantially limits the inhibitory effects of tumor necrosis factor-alpha to suppress IRS1 and IRS2 tyrosine phosphorylation, phosphatidylinositol 3-kinase activity, and glucose uptake in adipocytes. |
| 2975 | 15181014 | The ameliorated insulin signaling in SOCS3-deficient adipocytes is mainly due to the suppression of tumor necrosis factor-alpha-induced IRS1 and IRS2 protein degradation. |
| 2976 | 15181014 | Therefore, our data suggest that endogenous SOCS3 expression is a key determinant of basal insulin signaling and is an important molecular mediator of cytokine-induced insulin resistance in adipocytes. |
| 2977 | 15181014 | We conclude that SOCS3 plays an important role in mediating insulin resistance and may be an excellent target for therapeutic intervention in insulin resistance and type II diabetes. |
| 2978 | 15181014 | Suppressor of cytokine signaling 3 is a physiological regulator of adipocyte insulin signaling. |
| 2979 | 15181014 | We observed that several cytokines and hormones that induce insulin resistance also stimulate SOCS3 expression in 3T3-L1 adipocytes and that SOCS3 mRNA is increased in adipose tissue of obese/diabetic mice. |
| 2980 | 15181014 | We then hypothesized that SOCS3 may mediate cytokine- and hormone-induced insulin resistance. |
| 2981 | 15181014 | By using SOCS3-deficient adipocytes differentiated from mouse embryonic fibroblasts, we found that SOCS3 deficiency increases insulin-stimulated IRS1 and IRS2 phosphorylation, IRS-associated phosphatidylinositol 3-kinase activity, and insulin-stimulated glucose uptake. |
| 2982 | 15181014 | Moreover, lack of SOCS3 substantially limits the inhibitory effects of tumor necrosis factor-alpha to suppress IRS1 and IRS2 tyrosine phosphorylation, phosphatidylinositol 3-kinase activity, and glucose uptake in adipocytes. |
| 2983 | 15181014 | The ameliorated insulin signaling in SOCS3-deficient adipocytes is mainly due to the suppression of tumor necrosis factor-alpha-induced IRS1 and IRS2 protein degradation. |
| 2984 | 15181014 | Therefore, our data suggest that endogenous SOCS3 expression is a key determinant of basal insulin signaling and is an important molecular mediator of cytokine-induced insulin resistance in adipocytes. |
| 2985 | 15181014 | We conclude that SOCS3 plays an important role in mediating insulin resistance and may be an excellent target for therapeutic intervention in insulin resistance and type II diabetes. |
| 2986 | 15181089 | After washing, basal and insulin-stimulated [14C]glucose uptake as well as cellular content of insulin signaling proteins and glucose transporter 4 (GLUT4) was assessed. |
| 2987 | 15181089 | The cellular content of insulin receptor substrate 1 and phosphatidylinositol 3-kinase did not differ significantly between the depots, but the expression of protein kinase B (PKB) tended to be increased in omental compared with s.c. adipocytes (P = 0.09). |
| 2988 | 15181089 | Dexamethasone treatment decreased the expression of insulin receptor substrate 1 (by approximately 40%; P < 0.05) and PKB (by approximately 20%; P < 0.05) in omental but not in s.c. adipocytes. |
| 2989 | 15181089 | In contrast, dexamethasone pretreatment had no effect on insulin-stimulated Ser473 phosphorylation of PKB. |
| 2990 | 15249172 | The insulin stimulation of glucose uptake in adipocytes was selectively abolished by the phosphatidylinositol 3-kinase inhibitor wortmannin, whereas that by the adrenergic agonists, phenylephrine and isoproterenol, was inhibited by prazosin and propranolol, respectively. |
| 2991 | 15254873 | Hepatic phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase) activity was measured. |
| 2992 | 15254873 | Insulin signaling response was examined after insulin injection in the fast state by analyzing tyrosine phosphorylation of insulin receptor (IR) and the association between insulin receptor substrate-1 (IRS-1) and IRS-2 with phosphatidylinositol 3 kinase (PI3-K). |
| 2993 | 15254873 | After insulin administration in the fast state, tyrosine phosphorylation of IR and association of IRS-2 with PI3-K were higher in the EH and CL groups than in the CH group. |
| 2994 | 15254873 | Hepatic phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase) activity was measured. |
| 2995 | 15254873 | Insulin signaling response was examined after insulin injection in the fast state by analyzing tyrosine phosphorylation of insulin receptor (IR) and the association between insulin receptor substrate-1 (IRS-1) and IRS-2 with phosphatidylinositol 3 kinase (PI3-K). |
| 2996 | 15254873 | After insulin administration in the fast state, tyrosine phosphorylation of IR and association of IRS-2 with PI3-K were higher in the EH and CL groups than in the CH group. |
| 2997 | 15265871 | Further, either depletion of mitochondria or adenoviral overexpression of superoxide dismutases, as well as inhibition of nitric-oxide synthase, abolished the metformin-enhanced phosphorylations and activities of AMPK, implicating that activation of AMPK by metformin might be mediated by the mitochondria-derived RNS. |
| 2998 | 15265871 | Furthermore, administration of metformin, which increased 3-nitrotyrosine staining in hearts of C57BL6, resulted in parallel activation of AMPK in the aorta and hearts of C57BL6 mice but not in those of endothelial nitric-oxide synthase (eNOS) knockout mice in which metformin had no effect on 3-nitrotyrosine staining. |
| 2999 | 15265871 | Because the eNOS knockout mice expressed normal levels of AMPK-alpha that was activated by 5-aminoimidazole-4-carboxamide riboside, an AMPK agonist, these data indicate that RNS generated by metformin is required for AMPK activation in vivo. |
| 3000 | 15265871 | In addition, metformin significantly increased the co-immunoprecipitation of AMPK and its upstream kinase, LKB1, in C57BL6 mice administered to metformin in vivo. |
| 3001 | 15265871 | Using pharmacological and genetic inhibitors, we found that inhibition of either c-Src or PI3K abolished AMPK that was enhanced by metformin. |
| 3002 | 15265871 | We conclude that activation of AMPK by metformin might be mediated by mitochondria-derived RNS, and activation of the c-Src/PI3K pathway might generate a metabolite or other molecule inside the cell to promote AMPK activation by the LKB1 complex. |
| 3003 | 15265871 | Further, either depletion of mitochondria or adenoviral overexpression of superoxide dismutases, as well as inhibition of nitric-oxide synthase, abolished the metformin-enhanced phosphorylations and activities of AMPK, implicating that activation of AMPK by metformin might be mediated by the mitochondria-derived RNS. |
| 3004 | 15265871 | Furthermore, administration of metformin, which increased 3-nitrotyrosine staining in hearts of C57BL6, resulted in parallel activation of AMPK in the aorta and hearts of C57BL6 mice but not in those of endothelial nitric-oxide synthase (eNOS) knockout mice in which metformin had no effect on 3-nitrotyrosine staining. |
| 3005 | 15265871 | Because the eNOS knockout mice expressed normal levels of AMPK-alpha that was activated by 5-aminoimidazole-4-carboxamide riboside, an AMPK agonist, these data indicate that RNS generated by metformin is required for AMPK activation in vivo. |
| 3006 | 15265871 | In addition, metformin significantly increased the co-immunoprecipitation of AMPK and its upstream kinase, LKB1, in C57BL6 mice administered to metformin in vivo. |
| 3007 | 15265871 | Using pharmacological and genetic inhibitors, we found that inhibition of either c-Src or PI3K abolished AMPK that was enhanced by metformin. |
| 3008 | 15265871 | We conclude that activation of AMPK by metformin might be mediated by mitochondria-derived RNS, and activation of the c-Src/PI3K pathway might generate a metabolite or other molecule inside the cell to promote AMPK activation by the LKB1 complex. |
| 3009 | 15277220 | Insulin-like growth factor-I plays a pathogenetic role in diabetic retinopathy. |
| 3010 | 15277220 | In the current study, the role of insulin-like growth factor (IGF)-I in these processes was investigated. |
| 3011 | 15277220 | We found that systemic inhibition of IGF-I signaling with a receptor-neutralizing antibody, or with inhibitors of PI-3 kinase (PI-3K), c-Jun kinase (JNK), or Akt, suppressed retinal Akt, JNK, HIF-1alpha, nuclear factor (NF)-kappaB, and AP-1 activity, vascular endothelial growth factor (VEGF) expression, as well as intercellular adhesion molecule-1 levels, leukostasis, and blood-retinal barrier breakdown, in a relevant animal model. |
| 3012 | 15277220 | Intravitreous administration of IGF-I increased retinal Akt, JNK, HIF-1alpha, NF-kappaB, and AP-1 activity, and VEGF levels. |
| 3013 | 15277220 | IGF-I stimulated VEGF promoter activity in vitro, mainly via HIF-1alpha, and secondarily via NF-kappaB and AP-1. |
| 3014 | 15277220 | In conclusion, IGF-I participates in the pathophysiology of diabetic retinopathy by inducing retinal VEGF expression via PI-3K/Akt, HIF-1alpha, NF-kappaB, and secondarily, JNK/AP-1 activation. |
| 3015 | 15277220 | Insulin-like growth factor-I plays a pathogenetic role in diabetic retinopathy. |
| 3016 | 15277220 | In the current study, the role of insulin-like growth factor (IGF)-I in these processes was investigated. |
| 3017 | 15277220 | We found that systemic inhibition of IGF-I signaling with a receptor-neutralizing antibody, or with inhibitors of PI-3 kinase (PI-3K), c-Jun kinase (JNK), or Akt, suppressed retinal Akt, JNK, HIF-1alpha, nuclear factor (NF)-kappaB, and AP-1 activity, vascular endothelial growth factor (VEGF) expression, as well as intercellular adhesion molecule-1 levels, leukostasis, and blood-retinal barrier breakdown, in a relevant animal model. |
| 3018 | 15277220 | Intravitreous administration of IGF-I increased retinal Akt, JNK, HIF-1alpha, NF-kappaB, and AP-1 activity, and VEGF levels. |
| 3019 | 15277220 | IGF-I stimulated VEGF promoter activity in vitro, mainly via HIF-1alpha, and secondarily via NF-kappaB and AP-1. |
| 3020 | 15277220 | In conclusion, IGF-I participates in the pathophysiology of diabetic retinopathy by inducing retinal VEGF expression via PI-3K/Akt, HIF-1alpha, NF-kappaB, and secondarily, JNK/AP-1 activation. |
| 3021 | 15277383 | Caspase-8 activity was reduced in cells cultured on matrix, whereas focal adhesion kinase (FAK), protein kinase B (PKB, or Akt), and extracellular signal-regulated kinase (ERK) phosphorylation was augmented. |
| 3022 | 15277383 | Treatment (4 h) with an anti-beta1 integrin antibody, with the ERK pathway inhibitor PD98059, and/or with the phosphatidylinositol 3-kinase inhibitor LY294002 augmented cell death on 804G matrix but not on pLL. |
| 3023 | 15314154 | Disruption of the SH2-B gene causes age-dependent insulin resistance and glucose intolerance. |
| 3024 | 15314154 | SH2-B, an Src homology 2 (SH2) and pleckstrin homology domain-containing adaptor protein, binds via its SH2 domain to insulin receptor in response to insulin; however, its physiological role remains unclear. |
| 3025 | 15314154 | Systemic deletion of SH2-B impaired insulin receptor activation and signaling in the liver, skeletal muscle, and fat, including tyrosine phosphorylation of insulin receptor substrate 1 (IRS1) and IRS2 and activation of the phosphatidylinositol 3-kinase/Akt and the Erk1/2 pathways. |
| 3026 | 15314154 | Moreover, SH2-B directly enhanced autophosphorylation of insulin receptor and tyrosine phosphorylation of IRS1 and IRS2 in an SH2 domain-dependent manner in cultured cells. |
| 3027 | 15314154 | Our data suggest that SH2-B is a physiological enhancer of insulin receptor activation and is required for maintaining normal insulin sensitivity and glucose homeostasis during aging. |
| 3028 | 15339744 | Evidence against a role for insulin-signaling proteins PI 3-kinase and Akt in insulin resistance in human skeletal muscle induced by short-term GH infusion. |
| 3029 | 15339744 | GLUT4 content and insulin signaling, as assessed by insulin receptor substrate (IRS)-1-associated phosphatidylinositol 3-kinase and Akt activity were determined. |
| 3030 | 15339744 | GH infusion did not change Akt protein expression, and insulin caused an approximately 13-fold increase in Akt activity (1,309 +/- 327 and 1,287 +/- 173%) after both GH and saline infusion. |
| 3031 | 15339744 | In conclusion, insulin resistance in skeletal muscle induced by short-term GH administration is not associated with detectable changes in the upstream insulin-signaling cascade or reduction in total GLUT4. |
| 3032 | 15339744 | Yet unknown mechanisms in insulin signaling downstream of Akt may be responsible. |
| 3033 | 15362491 | Incubation of either insulin or the juice in the presence of wortmannin (a phosphatidylinositol 3-kinase inhibitor) resulted in a marked inhibition of 3H-deoxyglucose by L6 myotubes compared to the uptake obtained with either insulin or the juice alone. |
| 3034 | 15372106 | Recent studies have suggested that local accumulation of fat metabolites inside skeletal muscle may activate a serine kinase cascade involving protein kinase C-theta (PKC-theta), leading to defects in insulin signaling and glucose transport in skeletal muscle. |
| 3035 | 15372106 | A 5-hour lipid infusion decreased insulin-stimulated skeletal muscle glucose uptake in the WT mice that was associated with 40-50% decreases in insulin-stimulated tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1) and IRS-1-associated PI3K activity. |
| 3036 | 15379552 | Identification of major ERK-related phosphorylation sites in Gab1. |
| 3037 | 15379552 | To address this question in this report we examined extracellular signal-regulated kinases 1/2 (ERK) specific serine/threonine phosphorylation of the entire Gab1 engaged in insulin signaling in more detail in vitro. |
| 3038 | 15379552 | To elucidate the ERK1/2-specific phosphorylation pattern of Gab1, we used phosphopeptide mapping by two-dimensional HPLC analysis. |
| 3039 | 15379552 | Our results demonstrate that ERK1/2 phosphorylate Gab1 at six serine/threonine residues (T312, S381, S454, T476, S581, S597) in consensus motifs for MAP kinase phosphorylation. |
| 3040 | 15379552 | The biological role of identified phosphorylation sites was proven by PI3K and Akt activity in intact cells. |
| 3041 | 15379552 | These data demonstrate that ERK1/2 modulate insulin action via Gab1 by targeting serine and threonine residues beside YXXM motifs. |
| 3042 | 15379552 | Accordingly, insulin signaling is blocked at the level of PI3K. |
| 3043 | 15379552 | Identification of major ERK-related phosphorylation sites in Gab1. |
| 3044 | 15379552 | To address this question in this report we examined extracellular signal-regulated kinases 1/2 (ERK) specific serine/threonine phosphorylation of the entire Gab1 engaged in insulin signaling in more detail in vitro. |
| 3045 | 15379552 | To elucidate the ERK1/2-specific phosphorylation pattern of Gab1, we used phosphopeptide mapping by two-dimensional HPLC analysis. |
| 3046 | 15379552 | Our results demonstrate that ERK1/2 phosphorylate Gab1 at six serine/threonine residues (T312, S381, S454, T476, S581, S597) in consensus motifs for MAP kinase phosphorylation. |
| 3047 | 15379552 | The biological role of identified phosphorylation sites was proven by PI3K and Akt activity in intact cells. |
| 3048 | 15379552 | These data demonstrate that ERK1/2 modulate insulin action via Gab1 by targeting serine and threonine residues beside YXXM motifs. |
| 3049 | 15379552 | Accordingly, insulin signaling is blocked at the level of PI3K. |
| 3050 | 15485656 | Phosphatidylinositol 3-kinase inhibitors reveal a unique mechanism of enhancing insulin secretion in 832/13 rat insulinoma cells. |
| 3051 | 15485656 | Increased insulin secretion can be mimicked in vitro by acute culture of 832/13 rat insulinoma cells with phosphatidylinositol 3-kinase (PI-3K) inhibitors, a treatment that would theoretically simulate insulin resistance. |
| 3052 | 15485656 | We demonstrate in this study that while the PI-3K inhibitors Wortmannin and LY294002 both block Akt phosphorylation, only LY29002 significantly augments insulin secretion. |
| 3053 | 15485656 | We conclude that while PI-3K may play a role in regulating insulin secretion, there are diverse effects of the established inhibitors of this enzyme on beta-cell insulin secretory responses. |
| 3054 | 15485656 | Phosphatidylinositol 3-kinase inhibitors reveal a unique mechanism of enhancing insulin secretion in 832/13 rat insulinoma cells. |
| 3055 | 15485656 | Increased insulin secretion can be mimicked in vitro by acute culture of 832/13 rat insulinoma cells with phosphatidylinositol 3-kinase (PI-3K) inhibitors, a treatment that would theoretically simulate insulin resistance. |
| 3056 | 15485656 | We demonstrate in this study that while the PI-3K inhibitors Wortmannin and LY294002 both block Akt phosphorylation, only LY29002 significantly augments insulin secretion. |
| 3057 | 15485656 | We conclude that while PI-3K may play a role in regulating insulin secretion, there are diverse effects of the established inhibitors of this enzyme on beta-cell insulin secretory responses. |
| 3058 | 15485656 | Phosphatidylinositol 3-kinase inhibitors reveal a unique mechanism of enhancing insulin secretion in 832/13 rat insulinoma cells. |
| 3059 | 15485656 | Increased insulin secretion can be mimicked in vitro by acute culture of 832/13 rat insulinoma cells with phosphatidylinositol 3-kinase (PI-3K) inhibitors, a treatment that would theoretically simulate insulin resistance. |
| 3060 | 15485656 | We demonstrate in this study that while the PI-3K inhibitors Wortmannin and LY294002 both block Akt phosphorylation, only LY29002 significantly augments insulin secretion. |
| 3061 | 15485656 | We conclude that while PI-3K may play a role in regulating insulin secretion, there are diverse effects of the established inhibitors of this enzyme on beta-cell insulin secretory responses. |
| 3062 | 15485656 | Phosphatidylinositol 3-kinase inhibitors reveal a unique mechanism of enhancing insulin secretion in 832/13 rat insulinoma cells. |
| 3063 | 15485656 | Increased insulin secretion can be mimicked in vitro by acute culture of 832/13 rat insulinoma cells with phosphatidylinositol 3-kinase (PI-3K) inhibitors, a treatment that would theoretically simulate insulin resistance. |
| 3064 | 15485656 | We demonstrate in this study that while the PI-3K inhibitors Wortmannin and LY294002 both block Akt phosphorylation, only LY29002 significantly augments insulin secretion. |
| 3065 | 15485656 | We conclude that while PI-3K may play a role in regulating insulin secretion, there are diverse effects of the established inhibitors of this enzyme on beta-cell insulin secretory responses. |
| 3066 | 15489860 | Enhanced insulin sensitivity, energy expenditure and thermogenesis in adipose-specific Pten suppression in mice. |
| 3067 | 15489860 | Pten is an important phosphatase, suppressing the phosphatidylinositol-3 kinase/Akt pathway. |
| 3068 | 15489860 | AdipoPten-KO mice showed lower body and adipose tissue weights despite hyperphagia and enhanced insulin sensitivity with induced phosphorylation of Akt in adipose tissue. |
| 3069 | 15489860 | AdipoPten-KO mice also showed marked hyperthermia and increased energy expenditure with induced mitochondriagenesis in adipose tissue, associated with marked reduction of p53, inactivation of Rb, phosphorylation of cyclic AMP response element binding protein (CREB) and increased expression of Ppargc1a, the gene that encodes peroxisome proliferative activated receptor gamma coactivator 1 alpha. |
| 3070 | 15489860 | Our results suggest that altered expression of adipose Pten could regulate insulin sensitivity and energy expenditure. |
| 3071 | 15504954 | Rapamycin specifically disrupted the positive transcriptional feedback loop between CCAAT/enhancer-binding protein-alpha and peroxisome proliferator-activated receptor-gamma (PPAR-gamma), two key transcription factors in adipogenesis, by directly targeting the transactivation activity of PPAR-gamma. |
| 3072 | 15504954 | The results of our further investigation have led us to propose a model in which the mTOR pathway and the phosphatidylinositol 3-kinase/Akt pathway act in parallel to regulate PPAR-gamma activation during adipogenesis by mediating nutrient availability and insulin signals, respectively. |
| 3073 | 15504975 | Podocyte-derived vascular endothelial growth factor mediates the stimulation of alpha3(IV) collagen production by transforming growth factor-beta1 in mouse podocytes. |
| 3074 | 15504975 | Exogenous VEGF(164) increased the production of alpha3(IV) collagen, an integral component of the glomerular basement membrane (GBM); this effect was completely prevented by SU5416, a pan-VEGF receptor inhibitor. |
| 3075 | 15504975 | The VEGF inhibitor also partially prevented the stimulation of alpha3(IV) collagen by transforming growth factor (TGF)-beta1, establishing a novel role for endogenous VEGF. |
| 3076 | 15504975 | However, VEGF did not influence the production of another novel chain of collagen IV, alpha5(IV) collagen, and SU5416 failed to reverse the known inhibitory effect of TGF-beta1 on alpha5(IV) collagen production. |
| 3077 | 15504975 | VEGF signaling proceeds via autophosphorylation of VEGFR-1 and activation of the phosphatidylinositol 3-kinase (PI3K) pathway. |
| 3078 | 15504975 | Thus, podocyte-derived VEGF operates in an autocrine loop, likely through VEGFR-1 and PI3K, to stimulate alpha3(IV) collagen production. |
| 3079 | 15504975 | Podocyte-derived vascular endothelial growth factor mediates the stimulation of alpha3(IV) collagen production by transforming growth factor-beta1 in mouse podocytes. |
| 3080 | 15504975 | Exogenous VEGF(164) increased the production of alpha3(IV) collagen, an integral component of the glomerular basement membrane (GBM); this effect was completely prevented by SU5416, a pan-VEGF receptor inhibitor. |
| 3081 | 15504975 | The VEGF inhibitor also partially prevented the stimulation of alpha3(IV) collagen by transforming growth factor (TGF)-beta1, establishing a novel role for endogenous VEGF. |
| 3082 | 15504975 | However, VEGF did not influence the production of another novel chain of collagen IV, alpha5(IV) collagen, and SU5416 failed to reverse the known inhibitory effect of TGF-beta1 on alpha5(IV) collagen production. |
| 3083 | 15504975 | VEGF signaling proceeds via autophosphorylation of VEGFR-1 and activation of the phosphatidylinositol 3-kinase (PI3K) pathway. |
| 3084 | 15504975 | Thus, podocyte-derived VEGF operates in an autocrine loop, likely through VEGFR-1 and PI3K, to stimulate alpha3(IV) collagen production. |
| 3085 | 15505117 | Impairment of PI3-K/Akt pathway underlies attenuated endothelial function in aorta of type 2 diabetic mouse model. |
| 3086 | 15505117 | The phosphatidylinositol 3-kinase (PI3-K) pathway, which activates serine/threonine protein kinase Akt, enhances endothelial nitric oxide synthase (eNOS) phosphorylation and nitric oxide (NO) production. |
| 3087 | 15505117 | We investigated the involvement of the PI3-K/Akt pathway in the relaxation responses to acetylcholine (ACh) and clonidine in a new type 2 diabetic model (streptozotocin plus nicotinamide-induced diabetic mice). |
| 3088 | 15505117 | In control mice, the clonidine-induced and insulin-induced relaxations were each abolished by LY294002 and by Wortmannin (inhibitors of PI3-K), and also by Akt-inhibitor treatment. |
| 3089 | 15505117 | The expression level of total Akt protein was significantly decreased in the diabetic mice aorta, but those for the p85 and p110gamma subunits of PI3-K were not. |
| 3090 | 15505117 | The clonidine-induced Ser-473 phosphorylation of Akt through PI3-K was significantly decreased in our model; however, that induced by ACh was not. |
| 3091 | 15505117 | These results suggest that relaxation responses and NO production mediated via the PI3-K/Akt pathway are decreased in this type 2 diabetic model. |
| 3092 | 15505117 | Impairment of PI3-K/Akt pathway underlies attenuated endothelial function in aorta of type 2 diabetic mouse model. |
| 3093 | 15505117 | The phosphatidylinositol 3-kinase (PI3-K) pathway, which activates serine/threonine protein kinase Akt, enhances endothelial nitric oxide synthase (eNOS) phosphorylation and nitric oxide (NO) production. |
| 3094 | 15505117 | We investigated the involvement of the PI3-K/Akt pathway in the relaxation responses to acetylcholine (ACh) and clonidine in a new type 2 diabetic model (streptozotocin plus nicotinamide-induced diabetic mice). |
| 3095 | 15505117 | In control mice, the clonidine-induced and insulin-induced relaxations were each abolished by LY294002 and by Wortmannin (inhibitors of PI3-K), and also by Akt-inhibitor treatment. |
| 3096 | 15505117 | The expression level of total Akt protein was significantly decreased in the diabetic mice aorta, but those for the p85 and p110gamma subunits of PI3-K were not. |
| 3097 | 15505117 | The clonidine-induced Ser-473 phosphorylation of Akt through PI3-K was significantly decreased in our model; however, that induced by ACh was not. |
| 3098 | 15505117 | These results suggest that relaxation responses and NO production mediated via the PI3-K/Akt pathway are decreased in this type 2 diabetic model. |
| 3099 | 15505117 | Impairment of PI3-K/Akt pathway underlies attenuated endothelial function in aorta of type 2 diabetic mouse model. |
| 3100 | 15505117 | The phosphatidylinositol 3-kinase (PI3-K) pathway, which activates serine/threonine protein kinase Akt, enhances endothelial nitric oxide synthase (eNOS) phosphorylation and nitric oxide (NO) production. |
| 3101 | 15505117 | We investigated the involvement of the PI3-K/Akt pathway in the relaxation responses to acetylcholine (ACh) and clonidine in a new type 2 diabetic model (streptozotocin plus nicotinamide-induced diabetic mice). |
| 3102 | 15505117 | In control mice, the clonidine-induced and insulin-induced relaxations were each abolished by LY294002 and by Wortmannin (inhibitors of PI3-K), and also by Akt-inhibitor treatment. |
| 3103 | 15505117 | The expression level of total Akt protein was significantly decreased in the diabetic mice aorta, but those for the p85 and p110gamma subunits of PI3-K were not. |
| 3104 | 15505117 | The clonidine-induced Ser-473 phosphorylation of Akt through PI3-K was significantly decreased in our model; however, that induced by ACh was not. |
| 3105 | 15505117 | These results suggest that relaxation responses and NO production mediated via the PI3-K/Akt pathway are decreased in this type 2 diabetic model. |
| 3106 | 15505117 | Impairment of PI3-K/Akt pathway underlies attenuated endothelial function in aorta of type 2 diabetic mouse model. |
| 3107 | 15505117 | The phosphatidylinositol 3-kinase (PI3-K) pathway, which activates serine/threonine protein kinase Akt, enhances endothelial nitric oxide synthase (eNOS) phosphorylation and nitric oxide (NO) production. |
| 3108 | 15505117 | We investigated the involvement of the PI3-K/Akt pathway in the relaxation responses to acetylcholine (ACh) and clonidine in a new type 2 diabetic model (streptozotocin plus nicotinamide-induced diabetic mice). |
| 3109 | 15505117 | In control mice, the clonidine-induced and insulin-induced relaxations were each abolished by LY294002 and by Wortmannin (inhibitors of PI3-K), and also by Akt-inhibitor treatment. |
| 3110 | 15505117 | The expression level of total Akt protein was significantly decreased in the diabetic mice aorta, but those for the p85 and p110gamma subunits of PI3-K were not. |
| 3111 | 15505117 | The clonidine-induced Ser-473 phosphorylation of Akt through PI3-K was significantly decreased in our model; however, that induced by ACh was not. |
| 3112 | 15505117 | These results suggest that relaxation responses and NO production mediated via the PI3-K/Akt pathway are decreased in this type 2 diabetic model. |
| 3113 | 15505117 | Impairment of PI3-K/Akt pathway underlies attenuated endothelial function in aorta of type 2 diabetic mouse model. |
| 3114 | 15505117 | The phosphatidylinositol 3-kinase (PI3-K) pathway, which activates serine/threonine protein kinase Akt, enhances endothelial nitric oxide synthase (eNOS) phosphorylation and nitric oxide (NO) production. |
| 3115 | 15505117 | We investigated the involvement of the PI3-K/Akt pathway in the relaxation responses to acetylcholine (ACh) and clonidine in a new type 2 diabetic model (streptozotocin plus nicotinamide-induced diabetic mice). |
| 3116 | 15505117 | In control mice, the clonidine-induced and insulin-induced relaxations were each abolished by LY294002 and by Wortmannin (inhibitors of PI3-K), and also by Akt-inhibitor treatment. |
| 3117 | 15505117 | The expression level of total Akt protein was significantly decreased in the diabetic mice aorta, but those for the p85 and p110gamma subunits of PI3-K were not. |
| 3118 | 15505117 | The clonidine-induced Ser-473 phosphorylation of Akt through PI3-K was significantly decreased in our model; however, that induced by ACh was not. |
| 3119 | 15505117 | These results suggest that relaxation responses and NO production mediated via the PI3-K/Akt pathway are decreased in this type 2 diabetic model. |
| 3120 | 15505117 | Impairment of PI3-K/Akt pathway underlies attenuated endothelial function in aorta of type 2 diabetic mouse model. |
| 3121 | 15505117 | The phosphatidylinositol 3-kinase (PI3-K) pathway, which activates serine/threonine protein kinase Akt, enhances endothelial nitric oxide synthase (eNOS) phosphorylation and nitric oxide (NO) production. |
| 3122 | 15505117 | We investigated the involvement of the PI3-K/Akt pathway in the relaxation responses to acetylcholine (ACh) and clonidine in a new type 2 diabetic model (streptozotocin plus nicotinamide-induced diabetic mice). |
| 3123 | 15505117 | In control mice, the clonidine-induced and insulin-induced relaxations were each abolished by LY294002 and by Wortmannin (inhibitors of PI3-K), and also by Akt-inhibitor treatment. |
| 3124 | 15505117 | The expression level of total Akt protein was significantly decreased in the diabetic mice aorta, but those for the p85 and p110gamma subunits of PI3-K were not. |
| 3125 | 15505117 | The clonidine-induced Ser-473 phosphorylation of Akt through PI3-K was significantly decreased in our model; however, that induced by ACh was not. |
| 3126 | 15505117 | These results suggest that relaxation responses and NO production mediated via the PI3-K/Akt pathway are decreased in this type 2 diabetic model. |
| 3127 | 15505117 | Impairment of PI3-K/Akt pathway underlies attenuated endothelial function in aorta of type 2 diabetic mouse model. |
| 3128 | 15505117 | The phosphatidylinositol 3-kinase (PI3-K) pathway, which activates serine/threonine protein kinase Akt, enhances endothelial nitric oxide synthase (eNOS) phosphorylation and nitric oxide (NO) production. |
| 3129 | 15505117 | We investigated the involvement of the PI3-K/Akt pathway in the relaxation responses to acetylcholine (ACh) and clonidine in a new type 2 diabetic model (streptozotocin plus nicotinamide-induced diabetic mice). |
| 3130 | 15505117 | In control mice, the clonidine-induced and insulin-induced relaxations were each abolished by LY294002 and by Wortmannin (inhibitors of PI3-K), and also by Akt-inhibitor treatment. |
| 3131 | 15505117 | The expression level of total Akt protein was significantly decreased in the diabetic mice aorta, but those for the p85 and p110gamma subunits of PI3-K were not. |
| 3132 | 15505117 | The clonidine-induced Ser-473 phosphorylation of Akt through PI3-K was significantly decreased in our model; however, that induced by ACh was not. |
| 3133 | 15505117 | These results suggest that relaxation responses and NO production mediated via the PI3-K/Akt pathway are decreased in this type 2 diabetic model. |
| 3134 | 15528954 | Cu/Zn superoxide dismutase (SOD) and phosphatidylinositol-3-kinase (PI3K) were also measured. |
| 3135 | 15528954 | Diabetes led to increased activity (45%) and expression (70%) of liver iNOS, an effect that was attenuated by insulin treatment both in vitro and in whole animals. |
| 3136 | 15528954 | Levels of PI3K protein were significantly lower in diabetic rats while insulin treatment markedly increased expression. |
| 3137 | 15528954 | Glycemic control via insulin administration was able to downregulate enhanced hepatic iNOS activity and expression in the liver observed in the diabetic state and improve SOD activity, responses that can potentially reduce the free radical damage associated with diabetes. |
| 3138 | 15528954 | Cu/Zn superoxide dismutase (SOD) and phosphatidylinositol-3-kinase (PI3K) were also measured. |
| 3139 | 15528954 | Diabetes led to increased activity (45%) and expression (70%) of liver iNOS, an effect that was attenuated by insulin treatment both in vitro and in whole animals. |
| 3140 | 15528954 | Levels of PI3K protein were significantly lower in diabetic rats while insulin treatment markedly increased expression. |
| 3141 | 15528954 | Glycemic control via insulin administration was able to downregulate enhanced hepatic iNOS activity and expression in the liver observed in the diabetic state and improve SOD activity, responses that can potentially reduce the free radical damage associated with diabetes. |
| 3142 | 15545519 | Resistin promotes smooth muscle cell proliferation through activation of extracellular signal-regulated kinase 1/2 and phosphatidylinositol 3-kinase pathways. |
| 3143 | 15561930 | The potential role of SOCS-3 in the interleukin-1beta-induced desensitization of insulin signaling in pancreatic beta-cells. |
| 3144 | 15561930 | Because effective insulin signaling is required for the optimal beta-cell function, we assessed the effect of IL-1beta on the insulin pathway in a rat pancreatic beta-cell line. |
| 3145 | 15561930 | We show that IL-1beta decreases insulin-induced tyrosine phosphorylation of the insulin receptor (IR) and insulin receptor substrate (IRS) proteins as well as phosphatidylinositol 3-kinase (PI3K) activation, and that this action is not due to the IL-1beta-dependent nitric oxide (NO) production in RINm5F cells. |
| 3146 | 15561930 | We next analyzed if suppressor of cytokine signaling (SOCS)-3, which can be induced by multiple cytokines and which we identified as an insulin action inhibitor, was implicated in the IL-1beta inhibitory effect on insulin signaling in these cells. |
| 3147 | 15561930 | We show that IL-1beta increases SOCS-3 expression and induces SOCS-3/IR complex formation in RINm5F cells. |
| 3148 | 15561930 | Moreover, we find that ectopically expressed SOCS-3 associates with the IR and reduces insulin-dependent IR autophosphorylation and IRS/PI3K pathway in a way comparable to IL-1beta treatment in RINm5F cells. |
| 3149 | 15561930 | We propose that IL-1beta decreases insulin action in beta-cells through the induction of SOCS-3 expression, and that this effect potentially alters insulin-induced beta-cell survival. |
| 3150 | 15561930 | The potential role of SOCS-3 in the interleukin-1beta-induced desensitization of insulin signaling in pancreatic beta-cells. |
| 3151 | 15561930 | Because effective insulin signaling is required for the optimal beta-cell function, we assessed the effect of IL-1beta on the insulin pathway in a rat pancreatic beta-cell line. |
| 3152 | 15561930 | We show that IL-1beta decreases insulin-induced tyrosine phosphorylation of the insulin receptor (IR) and insulin receptor substrate (IRS) proteins as well as phosphatidylinositol 3-kinase (PI3K) activation, and that this action is not due to the IL-1beta-dependent nitric oxide (NO) production in RINm5F cells. |
| 3153 | 15561930 | We next analyzed if suppressor of cytokine signaling (SOCS)-3, which can be induced by multiple cytokines and which we identified as an insulin action inhibitor, was implicated in the IL-1beta inhibitory effect on insulin signaling in these cells. |
| 3154 | 15561930 | We show that IL-1beta increases SOCS-3 expression and induces SOCS-3/IR complex formation in RINm5F cells. |
| 3155 | 15561930 | Moreover, we find that ectopically expressed SOCS-3 associates with the IR and reduces insulin-dependent IR autophosphorylation and IRS/PI3K pathway in a way comparable to IL-1beta treatment in RINm5F cells. |
| 3156 | 15561930 | We propose that IL-1beta decreases insulin action in beta-cells through the induction of SOCS-3 expression, and that this effect potentially alters insulin-induced beta-cell survival. |
| 3157 | 15561953 | Glucose-oxidized LDL resulted in phosphorylation of extracellular signal-regulated kinase and protein kinase B/Akt and stimulated proliferation of isolated macrophages. |
| 3158 | 15561953 | The mitogenic effect of glucose-oxidized LDL was mediated by CD36 and by extracellular signal-regulated kinase activation induced by protein kinase C-dependent and phosphatidylinositol 3-kinase-dependent pathways. |
| 3159 | 15569940 | Identification and modulation of a caveolae-dependent signal pathway that regulates plasminogen activator inhibitor-1 in insulin-resistant adipocytes. |
| 3160 | 15569940 | Here, we show that perturbation of caveolar microdomains leads to insulin resistance and concomitant up-regulation of PAI-1 in 3T3L1 adipocytes. |
| 3161 | 15569940 | We present several lines of evidence showing that the phosphatidylinositol 3-kinase (PI3K) pathway negatively regulates PAI-1 gene expression. |
| 3162 | 15569940 | Insulin-induced PAI-1 gene expression is up-regulated by a specific inhibitor of PI3K. |
| 3163 | 15569940 | In addition, serum PAI-1 level is elevated in protein kinase Balpha-deficient mice, whereas it is reduced in p70 ribosomal S6 kinase 1-deficient mice. |
| 3164 | 15569940 | The PI3K pathway phosphorylates retinoblastoma protein (pRB), known to release free E2 (adenoviral protein) factor (E2F), which we have previously demonstrated to be a transcriptional repressor of PAI-1 gene expression. |
| 3165 | 15569940 | Accordingly, cell-penetrating peptides that disrupt pRB-E2F interaction, and thereby release free E2F, are able to suppress PAI-1 levels that are elevated during insulin-resistant conditions. |
| 3166 | 15569940 | This study identifies a caveolar-dependent signal pathway that up-regulates PAI-1 in insulin-resistant adipocytes and proposes a previously undescribed pharmacological paradigm of disrupting pRB-E2F interaction to suppress PAI-1 levels. |
| 3167 | 15569940 | Identification and modulation of a caveolae-dependent signal pathway that regulates plasminogen activator inhibitor-1 in insulin-resistant adipocytes. |
| 3168 | 15569940 | Here, we show that perturbation of caveolar microdomains leads to insulin resistance and concomitant up-regulation of PAI-1 in 3T3L1 adipocytes. |
| 3169 | 15569940 | We present several lines of evidence showing that the phosphatidylinositol 3-kinase (PI3K) pathway negatively regulates PAI-1 gene expression. |
| 3170 | 15569940 | Insulin-induced PAI-1 gene expression is up-regulated by a specific inhibitor of PI3K. |
| 3171 | 15569940 | In addition, serum PAI-1 level is elevated in protein kinase Balpha-deficient mice, whereas it is reduced in p70 ribosomal S6 kinase 1-deficient mice. |
| 3172 | 15569940 | The PI3K pathway phosphorylates retinoblastoma protein (pRB), known to release free E2 (adenoviral protein) factor (E2F), which we have previously demonstrated to be a transcriptional repressor of PAI-1 gene expression. |
| 3173 | 15569940 | Accordingly, cell-penetrating peptides that disrupt pRB-E2F interaction, and thereby release free E2F, are able to suppress PAI-1 levels that are elevated during insulin-resistant conditions. |
| 3174 | 15569940 | This study identifies a caveolar-dependent signal pathway that up-regulates PAI-1 in insulin-resistant adipocytes and proposes a previously undescribed pharmacological paradigm of disrupting pRB-E2F interaction to suppress PAI-1 levels. |
| 3175 | 15569940 | Identification and modulation of a caveolae-dependent signal pathway that regulates plasminogen activator inhibitor-1 in insulin-resistant adipocytes. |
| 3176 | 15569940 | Here, we show that perturbation of caveolar microdomains leads to insulin resistance and concomitant up-regulation of PAI-1 in 3T3L1 adipocytes. |
| 3177 | 15569940 | We present several lines of evidence showing that the phosphatidylinositol 3-kinase (PI3K) pathway negatively regulates PAI-1 gene expression. |
| 3178 | 15569940 | Insulin-induced PAI-1 gene expression is up-regulated by a specific inhibitor of PI3K. |
| 3179 | 15569940 | In addition, serum PAI-1 level is elevated in protein kinase Balpha-deficient mice, whereas it is reduced in p70 ribosomal S6 kinase 1-deficient mice. |
| 3180 | 15569940 | The PI3K pathway phosphorylates retinoblastoma protein (pRB), known to release free E2 (adenoviral protein) factor (E2F), which we have previously demonstrated to be a transcriptional repressor of PAI-1 gene expression. |
| 3181 | 15569940 | Accordingly, cell-penetrating peptides that disrupt pRB-E2F interaction, and thereby release free E2F, are able to suppress PAI-1 levels that are elevated during insulin-resistant conditions. |
| 3182 | 15569940 | This study identifies a caveolar-dependent signal pathway that up-regulates PAI-1 in insulin-resistant adipocytes and proposes a previously undescribed pharmacological paradigm of disrupting pRB-E2F interaction to suppress PAI-1 levels. |
| 3183 | 15588682 | Merrill and Perry (Myrtaceae) (commonly referred to as clove) extract acts like insulin in hepatocytes and hepatoma cells by reducing phosphoenolpyruvate carboxykinase (PEPCK) and glucose 6-phosphatase (G6Pase) gene expression. |
| 3184 | 15588682 | Much like insulin, clove-mediated repression is reversed by PI3K inhibitors and N-acetylcysteine (NAC). |
| 3185 | 15590636 | To determine the molecular mechanism by which this polymorphism may be linked to insulin resistance, we produced recombinant peptides comprising amino acid residues 925-1008 from IRS-1 that contain either a glycine or arginine at codon 972 and the two nearby tyrosine phosphorylation consensus sites (EY(941)MLM and DY(989)MTM), which are known binding sites for the p85alpha regulatory subunit of phosphatidylinositol 3-kinase. |
| 3186 | 15590636 | The use of additional overlapping fragments localized this interaction to domains between residues 950-986 of IRS-1 and residues 966-1271 of the insulin receptor, containing the tyrosine kinase domain of the receptor. |
| 3187 | 15590636 | In addition, the IRS-1-(925-1008) G972R peptide acted as a competitive inhibitor of insulin receptor and insulin-like growth factor-1 receptor autophosphorylation. |
| 3188 | 15590636 | Taken together, these data indicate that the G972R naturally occurring polymorphism of IRS-1 not only reduces phosphorylation of the substrate but allows IRS-1 to act as an inhibitor of the insulin receptor kinase, producing global insulin resistance. |
| 3189 | 15596543 | Wortmannin suppressed betacellulin-induced Pax4 expression, implicating the phosphatidylinositol 3-kinase signaling pathway. |
| 3190 | 15596543 | Adenoviral overexpression of Pax4 caused a 3.5-fold increase in beta-cell proliferation with a concomitant 1.9-, 4-, and 5-fold increase in Bcl-xL (antiapoptotic), c-myc, and Id2 mRNA levels, respectively. |
| 3191 | 15596543 | Accordingly, Pax4 transactivated the Bcl-xL and c-myc promoters, whereas its diabetes-linked mutant was less efficient. |
| 3192 | 15596543 | Bcl-xL activity resulted in altered mitochondrial calcium levels and ATP production, explaining impaired glucose-induced insulin secretion in transduced islets. |
| 3193 | 15596543 | We propose that Pax4 is implicated in beta-cell plasticity through the activation of c-myc and potentially protected from apoptosis through Bcl-xL gene expression. |
| 3194 | 15606684 | The ability of these compounds to stimulate glucose uptake, glycogen and lipid synthesis in muscle, adipose and hepatic tissues and to inhibit gluconeogenesis, and the activities of the gluconeogenic enzymes: phosphoenol pyruvate carboxykinase and glucose-6-phosphatase in the liver and kidney as well as lipolysis in fat cells contributes as potential mechanisms to their anti-diabetic insulin-like effects. |
| 3195 | 15606684 | At the cellular level, vanadium activates several key elements of the insulin signal transduction pathway, such as the tyrosine phosphorylation of insulin receptor substrate-1, and extracellular signal-regulated kinase 1 and 2, phosphatidylinositol 3-kinase and protein kinase B activation. |
| 3196 | 15632081 | Coordinated regulation of insulin signaling by the protein tyrosine phosphatases PTP1B and TCPTP. |
| 3197 | 15632081 | The protein tyrosine phosphatase PTP1B is a negative regulator of insulin signaling and a therapeutic target for type 2 diabetes. |
| 3198 | 15632081 | Our previous studies have shown that the closely related tyrosine phosphatase TCPTP might also contribute to the regulation of insulin receptor (IR) signaling in vivo (S. |
| 3199 | 15632081 | Here we show that PTP1B and TCPTP function in a coordinated and temporally distinct manner to achieve an overall regulation of IR phosphorylation and signaling. |
| 3200 | 15632081 | Whereas insulin-induced phosphatidylinositol 3-kinase/Akt signaling was prolonged in both TCPTP-/- and PTP1B-/- immortalized mouse embryo fibroblasts (MEFs), mitogen-activated protein kinase ERK1/2 signaling was elevated only in PTP1B-null MEFs. |
| 3201 | 15632081 | By using phosphorylation-specific antibodies, we demonstrate that both IR beta-subunit Y1162/Y1163 and Y972 phosphorylation are elevated in PTP1B-/- MEFs, whereas Y972 phosphorylation was elevated and Y1162/Y1163 phosphorylation was sustained in TCPTP-/- MEFs, indicating that PTP1B and TCPTP differentially contribute to the regulation of IR phosphorylation and signaling. |
| 3202 | 15632081 | Consistent with this, suppression of TCPTP protein levels by RNA interference in PTP1B-/- MEFs resulted in no change in ERK1/2 signaling but caused prolonged Akt activation and Y1162/Y1163 phosphorylation. |
| 3203 | 15632081 | These results demonstrate that PTP1B and TCPTP are not redundant in insulin signaling and that they act to control both common as well as distinct insulin signaling pathways in the same cell. |
| 3204 | 15649433 | Expression of the KLF15 gene in mouse liver was also down-regulated by a euglycemic-hyperinsulinemic clamp and was increased by inhibition of phosphatidylinositol 3-kinase. |
| 3205 | 15649433 | In cultured rat hepatocytes, KLF15 gene expression was induced by dexamethasone and a non-hydrolyzing analog of cAMP, and this effect was inhibited by insulin in a manner dependent on phosphatidylinositol 3-kinase signaling. |
| 3206 | 15649433 | Forced expression of KLF15 in cultured hepatocytes increased both the expression and the promoter activity of the gene for phosphoenolpyruvate carboxykinase (PEPCK). |
| 3207 | 15649433 | These results suggest that insulin and its counteracting hormones regulate the hepatic expression of KLF15, and that this transcription factor contributes to the regulation of PEPCK gene expression in the liver. |
| 3208 | 15649433 | Expression of the KLF15 gene in mouse liver was also down-regulated by a euglycemic-hyperinsulinemic clamp and was increased by inhibition of phosphatidylinositol 3-kinase. |
| 3209 | 15649433 | In cultured rat hepatocytes, KLF15 gene expression was induced by dexamethasone and a non-hydrolyzing analog of cAMP, and this effect was inhibited by insulin in a manner dependent on phosphatidylinositol 3-kinase signaling. |
| 3210 | 15649433 | Forced expression of KLF15 in cultured hepatocytes increased both the expression and the promoter activity of the gene for phosphoenolpyruvate carboxykinase (PEPCK). |
| 3211 | 15649433 | These results suggest that insulin and its counteracting hormones regulate the hepatic expression of KLF15, and that this transcription factor contributes to the regulation of PEPCK gene expression in the liver. |
| 3212 | 15653324 | The lipid kinase phosphoinositide 3-kinase (PI3K) is activated in response to various extracellular signals including peptide growth factors such as insulin and insulin-like growth factors (IGFs). |
| 3213 | 15653324 | Phosphatidylinositol (3,4,5)-trisphosphate [PtdIns(3,4,5)P(3)] generated by PI3K is central to the diverse responses elicited by insulin, including glucose homeostasis, proliferation, survival and cell growth. |
| 3214 | 15653324 | The actions of lipid phosphatases have been considered to be the main means of attenuating PI3K signalling, whereby the principal 3-phosphatase - phosphatase and tensin homologue deleted on chromosome 10 (PTEN) - dephosphorylates PtdIns(3,4,5)P(3), reversing the action of PI3K. |
| 3215 | 15653324 | This finding, together with earlier work, strongly suggests that a major form of negative feedback inhibition of PI3K results from activated growth signalling via mammalian target of rapamycin (mTOR) and the p70 S6 kinase (S6K) - a pathway that could have consequences for the development of type 2 diabetes and tuberous sclerosis complex. |
| 3216 | 15653324 | The lipid kinase phosphoinositide 3-kinase (PI3K) is activated in response to various extracellular signals including peptide growth factors such as insulin and insulin-like growth factors (IGFs). |
| 3217 | 15653324 | Phosphatidylinositol (3,4,5)-trisphosphate [PtdIns(3,4,5)P(3)] generated by PI3K is central to the diverse responses elicited by insulin, including glucose homeostasis, proliferation, survival and cell growth. |
| 3218 | 15653324 | The actions of lipid phosphatases have been considered to be the main means of attenuating PI3K signalling, whereby the principal 3-phosphatase - phosphatase and tensin homologue deleted on chromosome 10 (PTEN) - dephosphorylates PtdIns(3,4,5)P(3), reversing the action of PI3K. |
| 3219 | 15653324 | This finding, together with earlier work, strongly suggests that a major form of negative feedback inhibition of PI3K results from activated growth signalling via mammalian target of rapamycin (mTOR) and the p70 S6 kinase (S6K) - a pathway that could have consequences for the development of type 2 diabetes and tuberous sclerosis complex. |
| 3220 | 15653324 | The lipid kinase phosphoinositide 3-kinase (PI3K) is activated in response to various extracellular signals including peptide growth factors such as insulin and insulin-like growth factors (IGFs). |
| 3221 | 15653324 | Phosphatidylinositol (3,4,5)-trisphosphate [PtdIns(3,4,5)P(3)] generated by PI3K is central to the diverse responses elicited by insulin, including glucose homeostasis, proliferation, survival and cell growth. |
| 3222 | 15653324 | The actions of lipid phosphatases have been considered to be the main means of attenuating PI3K signalling, whereby the principal 3-phosphatase - phosphatase and tensin homologue deleted on chromosome 10 (PTEN) - dephosphorylates PtdIns(3,4,5)P(3), reversing the action of PI3K. |
| 3223 | 15653324 | This finding, together with earlier work, strongly suggests that a major form of negative feedback inhibition of PI3K results from activated growth signalling via mammalian target of rapamycin (mTOR) and the p70 S6 kinase (S6K) - a pathway that could have consequences for the development of type 2 diabetes and tuberous sclerosis complex. |
| 3224 | 15653324 | The lipid kinase phosphoinositide 3-kinase (PI3K) is activated in response to various extracellular signals including peptide growth factors such as insulin and insulin-like growth factors (IGFs). |
| 3225 | 15653324 | Phosphatidylinositol (3,4,5)-trisphosphate [PtdIns(3,4,5)P(3)] generated by PI3K is central to the diverse responses elicited by insulin, including glucose homeostasis, proliferation, survival and cell growth. |
| 3226 | 15653324 | The actions of lipid phosphatases have been considered to be the main means of attenuating PI3K signalling, whereby the principal 3-phosphatase - phosphatase and tensin homologue deleted on chromosome 10 (PTEN) - dephosphorylates PtdIns(3,4,5)P(3), reversing the action of PI3K. |
| 3227 | 15653324 | This finding, together with earlier work, strongly suggests that a major form of negative feedback inhibition of PI3K results from activated growth signalling via mammalian target of rapamycin (mTOR) and the p70 S6 kinase (S6K) - a pathway that could have consequences for the development of type 2 diabetes and tuberous sclerosis complex. |
| 3228 | 15654920 | The main pathway involved in insulin induction of adipogenic differentiation, monitored by fatty acid synthase expression, is the cascade insulin receptor substrate (IRS)-1/phosphatidylinositol 3-kinase (PI3K)/Akt. |
| 3229 | 15654920 | Acute insulin treatment stimulates glucose transport largely by mediating translocation of GLUT4 to the plasma membrane, involving the activation of IRS-2/PI3K, and the downstream targets Akt and protein kinase C zeta. |
| 3230 | 15654920 | Tumour necrosis factor (TNF-alpha) caused insulin resistance on glucose uptake by impairing insulin signalling at the level of IRS-2. |
| 3231 | 15654920 | Furthermore, brown adipocytes are also target cells for rosiglitazone action since they show a high expression of peroxisome proliferator activated receptor gamma, and rosiglitazone increased the expression of the thermogenic uncoupling protein 1. |
| 3232 | 15654920 | Rosiglitazone ameliorates insulin resistance provoked by TNF-alpha, completely restoring insulin-stimulated glucose uptake in parallel to the insulin signalling cascade. |
| 3233 | 15657439 | Muscle-specific Pten deletion protects against insulin resistance and diabetes. |
| 3234 | 15657439 | Pten (phosphatase with tensin homology), a dual-specificity phosphatase, is a negative regulator of the phosphoinositide 3-kinase (PI3K)/Akt signaling pathway. |
| 3235 | 15657439 | Although the PI3K/Akt pathway is a key determinant of the insulin-dependent increase in glucose uptake into muscle and adipose cells, the contribution of this pathway in muscle to whole-body glucose homeostasis is unclear. |
| 3236 | 15657439 | Here we show that muscle-specific deletion of Pten protected mice from insulin resistance and diabetes caused by high-fat feeding. |
| 3237 | 15657439 | Deletion of muscle Pten resulted in enhanced insulin-stimulated 2-deoxyglucose uptake and Akt phosphorylation in soleus but, surprisingly, not in extensor digitorum longus muscle compared to littermate controls upon high-fat feeding, and these mice were spared from developing hyperinsulinemia and islet hyperplasia. |
| 3238 | 15657439 | Muscle Pten may be a potential target for treatment or prevention of insulin resistance and diabetes. |
| 3239 | 15657439 | Muscle-specific Pten deletion protects against insulin resistance and diabetes. |
| 3240 | 15657439 | Pten (phosphatase with tensin homology), a dual-specificity phosphatase, is a negative regulator of the phosphoinositide 3-kinase (PI3K)/Akt signaling pathway. |
| 3241 | 15657439 | Although the PI3K/Akt pathway is a key determinant of the insulin-dependent increase in glucose uptake into muscle and adipose cells, the contribution of this pathway in muscle to whole-body glucose homeostasis is unclear. |
| 3242 | 15657439 | Here we show that muscle-specific deletion of Pten protected mice from insulin resistance and diabetes caused by high-fat feeding. |
| 3243 | 15657439 | Deletion of muscle Pten resulted in enhanced insulin-stimulated 2-deoxyglucose uptake and Akt phosphorylation in soleus but, surprisingly, not in extensor digitorum longus muscle compared to littermate controls upon high-fat feeding, and these mice were spared from developing hyperinsulinemia and islet hyperplasia. |
| 3244 | 15657439 | Muscle Pten may be a potential target for treatment or prevention of insulin resistance and diabetes. |
| 3245 | 15671078 | Type I soleus and type IIb epitrochlearis muscles from female obese Zucker rats were incubated in the absence or presence of a selective, small organic GSK3 inhibitor (1 microM CT118637, Ki < 10 nM for GSK3alpha and GSK3beta). |
| 3246 | 15671078 | Maximal insulin stimulation (5 mU/ml) of glucose transport activity, glycogen synthase activity, and selected insulin-signaling factors [tyrosine phosphorylation of insulin receptor (IR) and IRS-1, IRS-1 associated with p85 subunit of phosphatidylinositol 3-kinase, and serine phosphorylation of Akt and GSK3] were assessed. |
| 3247 | 15671078 | However, in obese soleus, GSK3 inhibition enhanced (all P < 0.05) insulin-stimulated IRS-1 tyrosine phosphorylation (45%), IRS-1-associated p85 (72%), Akt1/2 serine phosphorylation (30%), and GSK3beta serine phosphorylation (39%). |
| 3248 | 15671479 | Foxo1, a member of the Fox0 subfamily of winged-helix forkhead transcription factors, is a target of insulin and insulin-like growth factor-1 (IGF-1) signal transduction pathways that activate protein kinase B (PKB) in pancreatic beta cells. |
| 3249 | 15671479 | Foxo1 is a substrate for PKB, and its phosphorylation results in nuclear exclusion with concomitant alterations in gene expression that are important to cellular growth and differentiation. |
| 3250 | 15671479 | Because activation of PKB can require insulin receptor substrate proteins (IRS-1 and IRS-2) and phosphatidylinositol 3-kinase (PI3K), it is of interest to determine whether the activity of Foxo1 is also regulated by heterotrimeric G protein-coupled receptors (GPCRs) with IRS-1 or -2, PI3K, or PKB signaling potential. |
| 3251 | 15671479 | Indeed, studies of beta cells have demonstrated that activation of a GPCR for the blood glucose-lowering hormone GLP-1 leads to major alterations of IRS-2, PI3K, and PKB activity. |
| 3252 | 15671479 | By promoting nuclear exclusion of Foxo1 in a PKB-mediated manner, GLP-1 may up-regulate the expression of a homeodomain transcription factor (PDX-1) that serves as a master regulator of beta-cell growth and differentiation. |
| 3253 | 15671479 | Foxo1, a member of the Fox0 subfamily of winged-helix forkhead transcription factors, is a target of insulin and insulin-like growth factor-1 (IGF-1) signal transduction pathways that activate protein kinase B (PKB) in pancreatic beta cells. |
| 3254 | 15671479 | Foxo1 is a substrate for PKB, and its phosphorylation results in nuclear exclusion with concomitant alterations in gene expression that are important to cellular growth and differentiation. |
| 3255 | 15671479 | Because activation of PKB can require insulin receptor substrate proteins (IRS-1 and IRS-2) and phosphatidylinositol 3-kinase (PI3K), it is of interest to determine whether the activity of Foxo1 is also regulated by heterotrimeric G protein-coupled receptors (GPCRs) with IRS-1 or -2, PI3K, or PKB signaling potential. |
| 3256 | 15671479 | Indeed, studies of beta cells have demonstrated that activation of a GPCR for the blood glucose-lowering hormone GLP-1 leads to major alterations of IRS-2, PI3K, and PKB activity. |
| 3257 | 15671479 | By promoting nuclear exclusion of Foxo1 in a PKB-mediated manner, GLP-1 may up-regulate the expression of a homeodomain transcription factor (PDX-1) that serves as a master regulator of beta-cell growth and differentiation. |
| 3258 | 15684423 | Insulin regulates alternative splicing of PKCbetaII mRNA by phosphorylation of SRp40 via a phosphatidylinositol 3-kinase pathway (Patel, N. |
| 3259 | 15684423 | This study provides in vitro and in vivo evidence showing Akt2 kinase directly phosphorylated SRp40, thereby connecting the insulin, PI 3-kinase/Akt pathway with phosphorylation of a site on a nuclear splicing protein promoting exon inclusion. |
| 3260 | 15718270 | Both primary osteoblasts and the MC3T3-E1 osteoblast cell line express the RANTES receptors, CCR1, 3, 4, and 5 (by RT-PCR), which encode functional receptors in osteoblasts as shown by [125I]-RANTES binding followed by Scatchard analysis. |
| 3261 | 15718270 | Expression of all four RANTES receptor mRNAs in osteoblast is in contrast to the reports of expression of CCR1 being the only RANTES receptor expressed by osteoclasts. |
| 3262 | 15718270 | Exogenous RANTES elicits chemotaxis of osteoblasts and promotes cell survival via phosphatidylinositol 3-kinase with attendant phosphorylation of Akt. |
| 3263 | 15718270 | Osteoclastic RANTES, obtained from the conditioned medium of receptor activator of nuclear factor-kappa B ligand-differentiated RAW264.7 cells also induces chemotaxis of MC3T3-E1 cells. |
| 3264 | 15743841 | Insulin hypersensitivity and resistance to streptozotocin-induced diabetes in mice lacking PTEN in adipose tissue. |
| 3265 | 15743841 | In adipose tissue, insulin controls glucose and lipid metabolism through the intracellular mediators phosphatidylinositol 3-kinase and serine-threonine kinase AKT. |
| 3266 | 15743841 | Phosphatase and a tensin homolog deleted from chromosome 10 (PTEN), a negative regulator of the phosphatidylinositol 3-kinase/AKT pathway, is hypothesized to inhibit the metabolic effects of insulin. |
| 3267 | 15743841 | Loss of Pten results in improved systemic glucose tolerance and insulin sensitivity, associated with decreased fasting insulin levels, increased recruitment of the glucose transporter isoform 4 to the cell surface in adipose tissue, and decreased serum resistin levels. |
| 3268 | 15743841 | Our results demonstrate that in vivo PTEN is a potent negative regulator of insulin signaling and insulin sensitivity in adipose tissue. |
| 3269 | 15743841 | Furthermore, PTEN may be a promising target for nutritional and/or pharmacological interventions aimed at reversing insulin resistance. |
| 3270 | 15743841 | Insulin hypersensitivity and resistance to streptozotocin-induced diabetes in mice lacking PTEN in adipose tissue. |
| 3271 | 15743841 | In adipose tissue, insulin controls glucose and lipid metabolism through the intracellular mediators phosphatidylinositol 3-kinase and serine-threonine kinase AKT. |
| 3272 | 15743841 | Phosphatase and a tensin homolog deleted from chromosome 10 (PTEN), a negative regulator of the phosphatidylinositol 3-kinase/AKT pathway, is hypothesized to inhibit the metabolic effects of insulin. |
| 3273 | 15743841 | Loss of Pten results in improved systemic glucose tolerance and insulin sensitivity, associated with decreased fasting insulin levels, increased recruitment of the glucose transporter isoform 4 to the cell surface in adipose tissue, and decreased serum resistin levels. |
| 3274 | 15743841 | Our results demonstrate that in vivo PTEN is a potent negative regulator of insulin signaling and insulin sensitivity in adipose tissue. |
| 3275 | 15743841 | Furthermore, PTEN may be a promising target for nutritional and/or pharmacological interventions aimed at reversing insulin resistance. |
| 3276 | 15749807 | Prolonged insulin treatment inhibits GH signaling via STAT3 and STAT1. |
| 3277 | 15749807 | Previous studies in our laboratory have shown that GH induction of signal transducers and activators of transcription (STAT)5B tyrosine phosphorylation is inhibited by prolonged insulin treatment, probably via downregulation of GHR. |
| 3278 | 15749807 | Here, we find that in rat H4IIE hepatoma cells GH-induced tyrosine phosphorylation of two other STATs (STAT3 and STAT1) was also greatly reduced following prolonged insulin pretreatment compared with that induced by GH alone. |
| 3279 | 15749807 | In the present work, total STAT5B and STAT1 protein levels were not altered by prolonged insulin treatment. |
| 3280 | 15749807 | However, prolonged insulin treatment (16 h; 10 or 100 nM) resulted in a 30-40% reduction of total STAT3 protein, with little change at 0.1 and 1.0 nM insulin. |
| 3281 | 15749807 | Thus, there is a selective reduction of total STAT3 protein levels by insulin, but only at high concentration of insulin. |
| 3282 | 15749807 | Basal tyrosine phosphorylated (PY)-STAT3 was also significantly reduced by prolonged insulin treatment, and to a greater extent than total STAT3 protein levels. |
| 3283 | 15749807 | The inhibitory effect of insulin on total STAT3 protein and basal PY-STAT3 levels was dependent on activation of the MEK-ERK pathway, rather than the PI3K pathway. |
| 3284 | 15749807 | In contrast, the MEK-ERK pathway did not play a major role in insulin's inhibition of GH-induced PY-STAT3 and PY-STAT1. |
| 3285 | 15749807 | The present studies indicate that prolonged hyperinsulinemia, such as that found in some obese patients or patients with Type 2 diabetes mellitus, may have profound effects on GH signaling via STAT3 and STAT1. |
| 3286 | 15787604 | Atypical protein kinase C in insulin action and insulin resistance. |
| 3287 | 15787604 | It now seems clear that aPKC (atypical protein kinase C) isoforms are required for insulin-stimulated glucose transport in muscle and adipocytes. |
| 3288 | 15787604 | These defects in muscle aPKC activation are due to both impaired activation of insulin receptor substrate-1-dependent PI3K (phosphoinositide 3-kinase) and the direct activation of aPKCs by the lipid product of PI3K, PI-3,4,5-(PO4)3. |
| 3289 | 15793234 | Endoplasmic reticulum stress-induced apoptosis is partly mediated by reduced insulin signaling through phosphatidylinositol 3-kinase/Akt and increased glycogen synthase kinase-3beta in mouse insulinoma cells. |
| 3290 | 15793234 | Because insulin/IGF/Akt signaling has been implicated in beta-cell survival, we sought to determine whether this pathway is involved in ER stress-induced apoptosis. |
| 3291 | 15793234 | Stable cell lines were created by small-interfering RNA (siRNA) with graded reduction of insulin receptor expression, and these cells had enhanced susceptibility to ER stress-induced apoptosis and reduced levels of phospho-glycogen synthase kinase 3beta (GSK3beta). |
| 3292 | 15793234 | These results illustrate that ER stress-induced apoptosis is mediated at least in part by signaling through the phosphatidylinositol 3-kinase/Akt/GSK3beta pathway and that GSK3beta represents a novel target for agents to promote beta-cell survival. |
| 3293 | 15793234 | Endoplasmic reticulum stress-induced apoptosis is partly mediated by reduced insulin signaling through phosphatidylinositol 3-kinase/Akt and increased glycogen synthase kinase-3beta in mouse insulinoma cells. |
| 3294 | 15793234 | Because insulin/IGF/Akt signaling has been implicated in beta-cell survival, we sought to determine whether this pathway is involved in ER stress-induced apoptosis. |
| 3295 | 15793234 | Stable cell lines were created by small-interfering RNA (siRNA) with graded reduction of insulin receptor expression, and these cells had enhanced susceptibility to ER stress-induced apoptosis and reduced levels of phospho-glycogen synthase kinase 3beta (GSK3beta). |
| 3296 | 15793234 | These results illustrate that ER stress-induced apoptosis is mediated at least in part by signaling through the phosphatidylinositol 3-kinase/Akt/GSK3beta pathway and that GSK3beta represents a novel target for agents to promote beta-cell survival. |
| 3297 | 15824195 | Fatty acids appear to cause this defect in glucose transport by inhibiting insulin-stimulated tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1) and IRS-1 associated phosphatidylinositol 3-kinase activity. |
| 3298 | 15840010 | EPCs can be isolated from peripheral blood or bone marrow mononuclear cells, CD34(+) or CD133(+) hematopoietic progenitors. |
| 3299 | 15840010 | At the molecular level, these factors are well established to activate the phosphatidyl-inositol-3-kinase (PI3K)-Akt-dependent activation of the endothelial nitric oxide synthase (eNOS), suggesting that the PI3K-Akt-eNOS signaling pathway may be involved in the transduction of atheroprotective factors. |
| 3300 | 15857517 | Sensitization and translocation of TRPV1 by insulin and IGF-I. |
| 3301 | 15857517 | Insulin and insulin-like growth factors (IGFs) maintain vital neuronal functions. |
| 3302 | 15857517 | Absolute or functional deficiencies of insulin or IGF-I may contribute to neuronal and vascular complications associated with diabetes. |
| 3303 | 15857517 | Here we demonstrate that both insulin and IGF-I enhance TRPV1-mediated membrane currents in heterologous expression systems and cultured dorsal root ganglion neurons. |
| 3304 | 15857517 | Receptor tyrosine kinases trigger a signaling cascade leading to activation of phosphatidylinositol 3-kinase (PI(3)K) and protein kinase C (PKC)-mediated phosphorylation of TRPV1, which is found to be essential for the potentiation. |
| 3305 | 15928202 | Here, we show that lysophosphatidic acid (LPA) stimulates the production of PtdIns-3-P through activation of a class II PI3K (PI3K-C2beta). |
| 3306 | 15928202 | This study is the first identification of PtdIns-3-P and PI3K-C2beta as downstream effectors in LPA signaling and demonstration of an intracellular role for a class II PI3K. |
| 3307 | 15928202 | Defining this novel PI3K-C2beta-PtdIns-3-P signaling pathway may help clarify the process of cell migration and may shed new light on PI3K-mediated intracellular events. |
| 3308 | 15928202 | Here, we show that lysophosphatidic acid (LPA) stimulates the production of PtdIns-3-P through activation of a class II PI3K (PI3K-C2beta). |
| 3309 | 15928202 | This study is the first identification of PtdIns-3-P and PI3K-C2beta as downstream effectors in LPA signaling and demonstration of an intracellular role for a class II PI3K. |
| 3310 | 15928202 | Defining this novel PI3K-C2beta-PtdIns-3-P signaling pathway may help clarify the process of cell migration and may shed new light on PI3K-mediated intracellular events. |
| 3311 | 15928202 | Here, we show that lysophosphatidic acid (LPA) stimulates the production of PtdIns-3-P through activation of a class II PI3K (PI3K-C2beta). |
| 3312 | 15928202 | This study is the first identification of PtdIns-3-P and PI3K-C2beta as downstream effectors in LPA signaling and demonstration of an intracellular role for a class II PI3K. |
| 3313 | 15928202 | Defining this novel PI3K-C2beta-PtdIns-3-P signaling pathway may help clarify the process of cell migration and may shed new light on PI3K-mediated intracellular events. |
| 3314 | 15929863 | Fatty acids appear to cause this defect in glucose transport by inhibiting insulin-stimulated tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1) and IRS-1-associated phosphatidylinositol 3-kinase activity. |
| 3315 | 15935772 | The Phosphatidylinositol-3 kinase/Protein Kinase B (PI3K/PKB) signaling pathway controls growth, metabolism, and lifespan in animals, and deregulation of its activity is associated with diabetes and cancer in humans. |
| 3316 | 15935772 | Since Susi has no overt similarity to known inhibitors of PI3K/PKB signaling, it defines a novel mechanism by which this signaling cascade is kept in check. |
| 3317 | 15935772 | The Phosphatidylinositol-3 kinase/Protein Kinase B (PI3K/PKB) signaling pathway controls growth, metabolism, and lifespan in animals, and deregulation of its activity is associated with diabetes and cancer in humans. |
| 3318 | 15935772 | Since Susi has no overt similarity to known inhibitors of PI3K/PKB signaling, it defines a novel mechanism by which this signaling cascade is kept in check. |
| 3319 | 15964236 | The SH2 domain containing inositol polyphosphate 5-phosphatase-2: SHIP2. |
| 3320 | 15964236 | The SH2 domain containing inositol polyphosphate 5-phosphatase-2 (SHIP2) hydrolyzes phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3) generating phosphatidylinositol 3,4-bisphosphate (PtdIns(3,4)P2). |
| 3321 | 15964236 | Overexpression of SHIP2 inhibits insulin-stimulated phosphoinositide 3-kinase (PI3K) dependent signaling events. |
| 3322 | 15964236 | SHIP2 knockout mice were originally reported to show lethal neonatal hypoglycemia resulting from insulin hypersensitivity, but in addition to inactivating the SHIP2 gene, the Phox2a gene was also inadvertently deleted. |
| 3323 | 15964236 | Another SHIP2 knockout mouse has now been generated which inactivates the SHIP2 gene but leaves Phox2a intact. |
| 3324 | 15964918 | Hyperglycemia alters PI3k and Akt signaling and leads to endothelial cell proliferative dysfunction. |
| 3325 | 15964918 | We hypothesized that hyperglycemia decreases endothelial cell (EC) proliferation and survival via phosphatidylinositol 3-kinase (PI3k) and Akt signaling pathways. |
| 3326 | 15964918 | We assessed apoptosis by annexin V and propidium iodide staining and flow cytometry, analyzed cell lysates obtained on culture day 8 for total and phosphorylated PI3k and Akt by Western blot analysis, and measured Akt kinase activity using a GSK fusion protein. |
| 3327 | 15964918 | Apoptosis increased significantly in HUVEC exposed to 40 mM d-glucose. d-Glucose at 40 mM significantly decreased tyrosine-phosphorylated PI3k, threonine 308-phosphorylated-Akt, and Akt activity relative to control 5 mM d-glucose. |
| 3328 | 15964918 | Hyperglycemia alters PI3k and Akt signaling and leads to endothelial cell proliferative dysfunction. |
| 3329 | 15964918 | We hypothesized that hyperglycemia decreases endothelial cell (EC) proliferation and survival via phosphatidylinositol 3-kinase (PI3k) and Akt signaling pathways. |
| 3330 | 15964918 | We assessed apoptosis by annexin V and propidium iodide staining and flow cytometry, analyzed cell lysates obtained on culture day 8 for total and phosphorylated PI3k and Akt by Western blot analysis, and measured Akt kinase activity using a GSK fusion protein. |
| 3331 | 15964918 | Apoptosis increased significantly in HUVEC exposed to 40 mM d-glucose. d-Glucose at 40 mM significantly decreased tyrosine-phosphorylated PI3k, threonine 308-phosphorylated-Akt, and Akt activity relative to control 5 mM d-glucose. |
| 3332 | 15964918 | Hyperglycemia alters PI3k and Akt signaling and leads to endothelial cell proliferative dysfunction. |
| 3333 | 15964918 | We hypothesized that hyperglycemia decreases endothelial cell (EC) proliferation and survival via phosphatidylinositol 3-kinase (PI3k) and Akt signaling pathways. |
| 3334 | 15964918 | We assessed apoptosis by annexin V and propidium iodide staining and flow cytometry, analyzed cell lysates obtained on culture day 8 for total and phosphorylated PI3k and Akt by Western blot analysis, and measured Akt kinase activity using a GSK fusion protein. |
| 3335 | 15964918 | Apoptosis increased significantly in HUVEC exposed to 40 mM d-glucose. d-Glucose at 40 mM significantly decreased tyrosine-phosphorylated PI3k, threonine 308-phosphorylated-Akt, and Akt activity relative to control 5 mM d-glucose. |
| 3336 | 15964918 | Hyperglycemia alters PI3k and Akt signaling and leads to endothelial cell proliferative dysfunction. |
| 3337 | 15964918 | We hypothesized that hyperglycemia decreases endothelial cell (EC) proliferation and survival via phosphatidylinositol 3-kinase (PI3k) and Akt signaling pathways. |
| 3338 | 15964918 | We assessed apoptosis by annexin V and propidium iodide staining and flow cytometry, analyzed cell lysates obtained on culture day 8 for total and phosphorylated PI3k and Akt by Western blot analysis, and measured Akt kinase activity using a GSK fusion protein. |
| 3339 | 15964918 | Apoptosis increased significantly in HUVEC exposed to 40 mM d-glucose. d-Glucose at 40 mM significantly decreased tyrosine-phosphorylated PI3k, threonine 308-phosphorylated-Akt, and Akt activity relative to control 5 mM d-glucose. |
| 3340 | 15971149 | This study was mainly aimed at investigating the effect of potential inhibitors of distinct protein kinases and protein phosphatase-1 upon insulin- and GLP-1-stimulated 2-deoxy-D-glucose net uptake by normal rat skeletal muscle. |
| 3341 | 15971149 | The basal uptake of the D-glucose analog was decreased by wortmannin--a phosphatidylinositol-3-kinase inhibitor--, PD98059--a mitogen-activated protein kinases inhibitor--, and TNFalpha--a protein phosphatase-1 inhibitor--, but not by either rapamycin--a p70s6 kinase inhibitor--, or H-7--, a protein kinase C inhibitor--. |
| 3342 | 15971149 | The enhancing action of both insulin and GLP-1 upon 2-deoxy-D-glucose transport was abolished by PD98059 and H-7, but largely unaffected by TNFalpha. |
| 3343 | 15980869 | These effects of FSE on GLUT4 translocation and glucose uptake were inhibited by wortmannin, a phosphatidylinositol 3-kinase (PI3-K) inhibitor, and bisindolylmaleimide 1, a protein kinase C (PKC)-specific inhibitor. |
| 3344 | 15980869 | In vitro phosphorylation analysis revealed that, like insulin, FSE also induces tyrosine phosphorylation of a number of proteins including the insulin receptor, insulin receptor substrate 1 and p85 subunit of PI3-K, in both 3T3-L1 adipocytes and human hepatoma cells, HepG2. |
| 3345 | 15980869 | However, unlike insulin, FSE had no effect on protein kinase B (Akt) activation. |
| 3346 | 15980869 | These effects of FSE on GLUT4 translocation and glucose uptake were inhibited by wortmannin, a phosphatidylinositol 3-kinase (PI3-K) inhibitor, and bisindolylmaleimide 1, a protein kinase C (PKC)-specific inhibitor. |
| 3347 | 15980869 | In vitro phosphorylation analysis revealed that, like insulin, FSE also induces tyrosine phosphorylation of a number of proteins including the insulin receptor, insulin receptor substrate 1 and p85 subunit of PI3-K, in both 3T3-L1 adipocytes and human hepatoma cells, HepG2. |
| 3348 | 15980869 | However, unlike insulin, FSE had no effect on protein kinase B (Akt) activation. |
| 3349 | 16036906 | One mechanism is insulin-activated signaling through insulin receptor substrate-1 and phosphatidylinositol 3-kinase. |
| 3350 | 16036906 | However, more recent studies in transgenic and knockout animals show that AMP-activated protein kinase is not the sole mediator of the signal to GLUT4 translocation and suggest that there may be redundant signaling pathways leading to contraction-stimulated glucose transport. |
| 3351 | 16046410 | Expression of an uncleavable N-terminal RasGAP fragment in insulin-secreting cells increases their resistance toward apoptotic stimuli without affecting their glucose-induced insulin secretion. |
| 3352 | 16046410 | RasGAP, a regulator of Ras and Rho GTPases, is an atypical caspase substrate, since it inhibits, rather than favors, apoptosis when it is partially cleaved by caspase-3 at position 455. |
| 3353 | 16046410 | The antiapoptotic signal generated by the partial processing of RasGAP is mediated by the N-terminal fragment (fragment N) in a Ras-phosphatidylinositol 3-kinase-Akt-dependent, but NF-kappaB-independent, manner. |
| 3354 | 16046410 | Here we demonstrate that an uncleavable form of fragment N activates Akt, represses NF-kappaB activity, and protects the conditionally immortalized pancreatic insulinoma betaTC-tet cell line against various insults, including exposure to genotoxins, trophic support withdrawal, and incubation with inflammatory cytokines. |
| 3355 | 16087719 | We have investigated, in isolated rat adipocytes, the changes caused by GLP-1, Ex-4 and Ex-9 compared with those provoked by insulin or glucagon, upon the activity of phosphatidylinositol-3-kinase (PI3K), protein kinase B (PKB), p42/44 MAP kinases (MAPKs) and p70s6 kinase (p70s6k), and the participation of these kinases and protein kinase C (PKC) in their action upon 2-deoxy-d-glucose uptake, lipolysis and lipogenesis. |
| 3356 | 16087719 | In normal rat adipocytes, GLP-1 and both exendins share with insulin an increasing action upon the activity of all kinases studied (except PKB), PI3K, p44 and p42 MAPKs and possibly PKC, all being required for their stimulating effect upon glucose uptake. |
| 3357 | 16087719 | Ex-4 and Ex-9, like GLP-1 and insulin, have lipogenic action, while only Ex-4 shares with GLP-1 its lipolytic effect which is antagonized by Ex-9. |
| 3358 | 16087719 | MAP kinases and PKC seem to have an essential role in the GLP-1 and Ex-4 lipolytic action, as does PI3K in that of Ex-4. |
| 3359 | 16087719 | An increase in PI3K and MAPKs activity for the lipogenic effect of Ex-4, Ex-9 and GLP-1 are required, and in the case of Ex-4 and Ex-9, a stimulation of p70s6k activity is also needed. |
| 3360 | 16087719 | In cells from STZ-rats the magnitude of the above parameters was, in general, comparable to that in normal animals, with some exceptions: basal PI3K activity and lipogenesis were higher, GLP-1, Ex-4 and Ex-9 failed to modify basal lipogenesis but increased PKB activity, insulin failed to affect the activity of MAPKs and the insulin-induced glucose uptake was impaired. |
| 3361 | 16087719 | The impaired insulin effects upon some of the variables in the STZ-rat, distinct from those of GLP-1 and exendins, adds knowledge to the mechanism of the beneficial action of GLP-1 and Ex-4 in diabetic states. |
| 3362 | 16087719 | We have investigated, in isolated rat adipocytes, the changes caused by GLP-1, Ex-4 and Ex-9 compared with those provoked by insulin or glucagon, upon the activity of phosphatidylinositol-3-kinase (PI3K), protein kinase B (PKB), p42/44 MAP kinases (MAPKs) and p70s6 kinase (p70s6k), and the participation of these kinases and protein kinase C (PKC) in their action upon 2-deoxy-d-glucose uptake, lipolysis and lipogenesis. |
| 3363 | 16087719 | In normal rat adipocytes, GLP-1 and both exendins share with insulin an increasing action upon the activity of all kinases studied (except PKB), PI3K, p44 and p42 MAPKs and possibly PKC, all being required for their stimulating effect upon glucose uptake. |
| 3364 | 16087719 | Ex-4 and Ex-9, like GLP-1 and insulin, have lipogenic action, while only Ex-4 shares with GLP-1 its lipolytic effect which is antagonized by Ex-9. |
| 3365 | 16087719 | MAP kinases and PKC seem to have an essential role in the GLP-1 and Ex-4 lipolytic action, as does PI3K in that of Ex-4. |
| 3366 | 16087719 | An increase in PI3K and MAPKs activity for the lipogenic effect of Ex-4, Ex-9 and GLP-1 are required, and in the case of Ex-4 and Ex-9, a stimulation of p70s6k activity is also needed. |
| 3367 | 16087719 | In cells from STZ-rats the magnitude of the above parameters was, in general, comparable to that in normal animals, with some exceptions: basal PI3K activity and lipogenesis were higher, GLP-1, Ex-4 and Ex-9 failed to modify basal lipogenesis but increased PKB activity, insulin failed to affect the activity of MAPKs and the insulin-induced glucose uptake was impaired. |
| 3368 | 16087719 | The impaired insulin effects upon some of the variables in the STZ-rat, distinct from those of GLP-1 and exendins, adds knowledge to the mechanism of the beneficial action of GLP-1 and Ex-4 in diabetic states. |
| 3369 | 16087719 | We have investigated, in isolated rat adipocytes, the changes caused by GLP-1, Ex-4 and Ex-9 compared with those provoked by insulin or glucagon, upon the activity of phosphatidylinositol-3-kinase (PI3K), protein kinase B (PKB), p42/44 MAP kinases (MAPKs) and p70s6 kinase (p70s6k), and the participation of these kinases and protein kinase C (PKC) in their action upon 2-deoxy-d-glucose uptake, lipolysis and lipogenesis. |
| 3370 | 16087719 | In normal rat adipocytes, GLP-1 and both exendins share with insulin an increasing action upon the activity of all kinases studied (except PKB), PI3K, p44 and p42 MAPKs and possibly PKC, all being required for their stimulating effect upon glucose uptake. |
| 3371 | 16087719 | Ex-4 and Ex-9, like GLP-1 and insulin, have lipogenic action, while only Ex-4 shares with GLP-1 its lipolytic effect which is antagonized by Ex-9. |
| 3372 | 16087719 | MAP kinases and PKC seem to have an essential role in the GLP-1 and Ex-4 lipolytic action, as does PI3K in that of Ex-4. |
| 3373 | 16087719 | An increase in PI3K and MAPKs activity for the lipogenic effect of Ex-4, Ex-9 and GLP-1 are required, and in the case of Ex-4 and Ex-9, a stimulation of p70s6k activity is also needed. |
| 3374 | 16087719 | In cells from STZ-rats the magnitude of the above parameters was, in general, comparable to that in normal animals, with some exceptions: basal PI3K activity and lipogenesis were higher, GLP-1, Ex-4 and Ex-9 failed to modify basal lipogenesis but increased PKB activity, insulin failed to affect the activity of MAPKs and the insulin-induced glucose uptake was impaired. |
| 3375 | 16087719 | The impaired insulin effects upon some of the variables in the STZ-rat, distinct from those of GLP-1 and exendins, adds knowledge to the mechanism of the beneficial action of GLP-1 and Ex-4 in diabetic states. |
| 3376 | 16087719 | We have investigated, in isolated rat adipocytes, the changes caused by GLP-1, Ex-4 and Ex-9 compared with those provoked by insulin or glucagon, upon the activity of phosphatidylinositol-3-kinase (PI3K), protein kinase B (PKB), p42/44 MAP kinases (MAPKs) and p70s6 kinase (p70s6k), and the participation of these kinases and protein kinase C (PKC) in their action upon 2-deoxy-d-glucose uptake, lipolysis and lipogenesis. |
| 3377 | 16087719 | In normal rat adipocytes, GLP-1 and both exendins share with insulin an increasing action upon the activity of all kinases studied (except PKB), PI3K, p44 and p42 MAPKs and possibly PKC, all being required for their stimulating effect upon glucose uptake. |
| 3378 | 16087719 | Ex-4 and Ex-9, like GLP-1 and insulin, have lipogenic action, while only Ex-4 shares with GLP-1 its lipolytic effect which is antagonized by Ex-9. |
| 3379 | 16087719 | MAP kinases and PKC seem to have an essential role in the GLP-1 and Ex-4 lipolytic action, as does PI3K in that of Ex-4. |
| 3380 | 16087719 | An increase in PI3K and MAPKs activity for the lipogenic effect of Ex-4, Ex-9 and GLP-1 are required, and in the case of Ex-4 and Ex-9, a stimulation of p70s6k activity is also needed. |
| 3381 | 16087719 | In cells from STZ-rats the magnitude of the above parameters was, in general, comparable to that in normal animals, with some exceptions: basal PI3K activity and lipogenesis were higher, GLP-1, Ex-4 and Ex-9 failed to modify basal lipogenesis but increased PKB activity, insulin failed to affect the activity of MAPKs and the insulin-induced glucose uptake was impaired. |
| 3382 | 16087719 | The impaired insulin effects upon some of the variables in the STZ-rat, distinct from those of GLP-1 and exendins, adds knowledge to the mechanism of the beneficial action of GLP-1 and Ex-4 in diabetic states. |
| 3383 | 16087719 | We have investigated, in isolated rat adipocytes, the changes caused by GLP-1, Ex-4 and Ex-9 compared with those provoked by insulin or glucagon, upon the activity of phosphatidylinositol-3-kinase (PI3K), protein kinase B (PKB), p42/44 MAP kinases (MAPKs) and p70s6 kinase (p70s6k), and the participation of these kinases and protein kinase C (PKC) in their action upon 2-deoxy-d-glucose uptake, lipolysis and lipogenesis. |
| 3384 | 16087719 | In normal rat adipocytes, GLP-1 and both exendins share with insulin an increasing action upon the activity of all kinases studied (except PKB), PI3K, p44 and p42 MAPKs and possibly PKC, all being required for their stimulating effect upon glucose uptake. |
| 3385 | 16087719 | Ex-4 and Ex-9, like GLP-1 and insulin, have lipogenic action, while only Ex-4 shares with GLP-1 its lipolytic effect which is antagonized by Ex-9. |
| 3386 | 16087719 | MAP kinases and PKC seem to have an essential role in the GLP-1 and Ex-4 lipolytic action, as does PI3K in that of Ex-4. |
| 3387 | 16087719 | An increase in PI3K and MAPKs activity for the lipogenic effect of Ex-4, Ex-9 and GLP-1 are required, and in the case of Ex-4 and Ex-9, a stimulation of p70s6k activity is also needed. |
| 3388 | 16087719 | In cells from STZ-rats the magnitude of the above parameters was, in general, comparable to that in normal animals, with some exceptions: basal PI3K activity and lipogenesis were higher, GLP-1, Ex-4 and Ex-9 failed to modify basal lipogenesis but increased PKB activity, insulin failed to affect the activity of MAPKs and the insulin-induced glucose uptake was impaired. |
| 3389 | 16087719 | The impaired insulin effects upon some of the variables in the STZ-rat, distinct from those of GLP-1 and exendins, adds knowledge to the mechanism of the beneficial action of GLP-1 and Ex-4 in diabetic states. |
| 3390 | 16098829 | Accumulating evidence indicates an important role for serine phosphorylation of IRS-1 in the regulation of insulin action. |
| 3391 | 16098829 | Recent studies suggest that Rho-kinase (ROK) is a mediator of insulin signaling, via interaction with IRS-1. |
| 3392 | 16098829 | Inactivation of ROK also reduces insulin-stimulated IRS-1 tyrosine phosphorylation and PI3K activity. |
| 3393 | 16098829 | Mass spectrometry analysis identifies IRS-1 Ser632/635 as substrates of ROK in vitro, and mutation of these sites inhibits insulin signaling. |
| 3394 | 16105861 | Decreased insulin-dependent glucose transport by chronic ethanol feeding is associated with dysregulation of the Cbl/TC10 pathway in rat adipocytes. |
| 3395 | 16105861 | Insulin-stimulated glucose disposal in adipocytes is regulated by two separate and independent pathways, the PI3K pathway and the Cbl/TC10 pathway. |
| 3396 | 16105861 | Previous studies suggest that chronic ethanol feeding impairs insulin-stimulated glucose transport in adipocytes in a PI3K-independent manner. |
| 3397 | 16105861 | In search of potential targets of ethanol that would affect insulin-stimulated glucose transport, we investigated the effects of 4-wk ethanol feeding to male Wistar rats on the Cbl/TC10 pathway in isolated adipocytes. |
| 3398 | 16105861 | Insulin receptor and Akt/PKB phosphorylation were not affected by ethanol feeding. |
| 3399 | 16105861 | Chronic ethanol exposure also impaired cCbl and TC10 recruitment to a lipid raft fraction isolated from adipocytes by detergent extraction. |
| 3400 | 16105861 | These results demonstrate that the impairment in insulin-stimulated glucose transport observed in adipocytes after chronic ethanol feeding to rats is associated with a disruption of insulin-mediated Cbl/TC10 signaling and actin polymerization. |
| 3401 | 16105861 | Decreased insulin-dependent glucose transport by chronic ethanol feeding is associated with dysregulation of the Cbl/TC10 pathway in rat adipocytes. |
| 3402 | 16105861 | Insulin-stimulated glucose disposal in adipocytes is regulated by two separate and independent pathways, the PI3K pathway and the Cbl/TC10 pathway. |
| 3403 | 16105861 | Previous studies suggest that chronic ethanol feeding impairs insulin-stimulated glucose transport in adipocytes in a PI3K-independent manner. |
| 3404 | 16105861 | In search of potential targets of ethanol that would affect insulin-stimulated glucose transport, we investigated the effects of 4-wk ethanol feeding to male Wistar rats on the Cbl/TC10 pathway in isolated adipocytes. |
| 3405 | 16105861 | Insulin receptor and Akt/PKB phosphorylation were not affected by ethanol feeding. |
| 3406 | 16105861 | Chronic ethanol exposure also impaired cCbl and TC10 recruitment to a lipid raft fraction isolated from adipocytes by detergent extraction. |
| 3407 | 16105861 | These results demonstrate that the impairment in insulin-stimulated glucose transport observed in adipocytes after chronic ethanol feeding to rats is associated with a disruption of insulin-mediated Cbl/TC10 signaling and actin polymerization. |
| 3408 | 16130009 | Within the insulin-signaling cascade IRS-1 tyrosine phosphorylation was induced several fold by insulin and was diminished by preincubation with olanzapine. |
| 3409 | 16130009 | IRS-1-associated PI3K activity was stimulated by insulin three-fold in L6 myotubes. |
| 3410 | 16130009 | Olanzapine inhibited insulin-stimulated IRS-1-associated PI3K activity in a dose-dependent manner. |
| 3411 | 16130009 | Within the insulin-signaling cascade IRS-1 tyrosine phosphorylation was induced several fold by insulin and was diminished by preincubation with olanzapine. |
| 3412 | 16130009 | IRS-1-associated PI3K activity was stimulated by insulin three-fold in L6 myotubes. |
| 3413 | 16130009 | Olanzapine inhibited insulin-stimulated IRS-1-associated PI3K activity in a dose-dependent manner. |
| 3414 | 16142415 | Changes in the activity of glycogen synthase a and related kinases (phosphatidylinositol-3-kinase, protein kinase B, p44/42 MAP kinases and p70s6 kinase) evoked by GLP-1 in human myocytes from normal subjects were recently implied in the effect of this hormone upon D-glucose transport and glycogen synthesis in the same cells. |
| 3415 | 16142415 | Apart from the much higher basal PI3K activity and impaired response to insulin of p44/42 MAP kinases in the diabetic patients, the changes in enzyme activity caused by either hormone or peptide, although not identical, were essentially comparable. |
| 3416 | 16142415 | Changes in the activity of glycogen synthase a and related kinases (phosphatidylinositol-3-kinase, protein kinase B, p44/42 MAP kinases and p70s6 kinase) evoked by GLP-1 in human myocytes from normal subjects were recently implied in the effect of this hormone upon D-glucose transport and glycogen synthesis in the same cells. |
| 3417 | 16142415 | Apart from the much higher basal PI3K activity and impaired response to insulin of p44/42 MAP kinases in the diabetic patients, the changes in enzyme activity caused by either hormone or peptide, although not identical, were essentially comparable. |
| 3418 | 16151974 | This was paralleled by robust induction of insulin receptor kinase activity, insulin receptor substrate-1-associated phosphatidylinositol-3 kinase activity, and protein kinase B phosphorylation. |
| 3419 | 16151974 | By contrast, pretreatment with the beta (3)-adrenoceptor agonist inhibited the insulin-induced insulin receptor substrate-1-associated phosphatidylinositol-3 kinase activity by 50 % and protein kinase B phosphorylation by 40 % without affecting insulin receptor kinase activity upstream. |
| 3420 | 16151974 | This was paralleled by robust induction of insulin receptor kinase activity, insulin receptor substrate-1-associated phosphatidylinositol-3 kinase activity, and protein kinase B phosphorylation. |
| 3421 | 16151974 | By contrast, pretreatment with the beta (3)-adrenoceptor agonist inhibited the insulin-induced insulin receptor substrate-1-associated phosphatidylinositol-3 kinase activity by 50 % and protein kinase B phosphorylation by 40 % without affecting insulin receptor kinase activity upstream. |
| 3422 | 16166302 | In tumor cells with mutations in epidermal growth factor receptor (SQ20B), H-Ras (T24), or K-Ras (MIAPACA2 and A549), the inhibition of Akt phosphorylation increases radiation sensitivity in clonogenic assays, suggesting that Akt is a potential molecular target when combined with therapeutic radiation. |
| 3423 | 16166302 | Insulin resistance and diabetes are recognized side effects of HIV protease inhibitors (HPIs), suggesting that these agents may inhibit Akt signaling. |
| 3424 | 16166302 | Because activation of the phosphatidylinositol 3-kinase (PI3K)-Akt signaling pathway is common in human cancers, we hypothesized that HPIs can inhibit Akt activity resulting in increased tumor cell sensitivity to ionizing radiation-induced cell death. |
| 3425 | 16166302 | Finally, overexpression of active PI3K in cells without activation of Akt resulted in radiation resistance that could be inhibited with HPIs. |
| 3426 | 16166302 | In tumor cells with mutations in epidermal growth factor receptor (SQ20B), H-Ras (T24), or K-Ras (MIAPACA2 and A549), the inhibition of Akt phosphorylation increases radiation sensitivity in clonogenic assays, suggesting that Akt is a potential molecular target when combined with therapeutic radiation. |
| 3427 | 16166302 | Insulin resistance and diabetes are recognized side effects of HIV protease inhibitors (HPIs), suggesting that these agents may inhibit Akt signaling. |
| 3428 | 16166302 | Because activation of the phosphatidylinositol 3-kinase (PI3K)-Akt signaling pathway is common in human cancers, we hypothesized that HPIs can inhibit Akt activity resulting in increased tumor cell sensitivity to ionizing radiation-induced cell death. |
| 3429 | 16166302 | Finally, overexpression of active PI3K in cells without activation of Akt resulted in radiation resistance that could be inhibited with HPIs. |
| 3430 | 16170201 | The Irs2 branch of the insulin/insulin-like growth factor signaling cascade activates the phosphatidylinositol 3-kinase --> Akt --> Foxo1 cascade in many tissues, including hepatocytes and pancreatic beta-cells. |
| 3431 | 16170201 | To determine whether decreased Pten expression could restore beta-cell function and prevent diabetes in Irs2(-/-) mice, we generated wild type or Irs2 knock-out mice that were haploinsufficient for Pten (Irs2(-/-)::Pten(+/-)). |
| 3432 | 16170201 | Irs2(-/-) mice develop diabetes by 3 months of age as beta-cell mass declined progressively until insulin production was lost. |
| 3433 | 16170201 | Pten insufficiency increased peripheral insulin sensitivity in wild type and Irs2(-/-) mice and increased Akt and Foxo1 phosphorylation in the islets. |
| 3434 | 16170201 | Glucose tolerance improved in the Pten(+/-) mice, although beta-cell mass and circulating insulin levels decreased. |
| 3435 | 16170201 | Compared with Irs2(-/-) mice, the Irs2(-/-)::Pten(+/-) mice displayed nearly normal glucose tolerance and survived without diabetes, because normal but small islets produced sufficient insulin until the mice died of lymphoproliferative disease at 12 months age. |
| 3436 | 16170201 | Thus, steps to enhance phosphatidylinositol 3-kinase signaling can promote beta-cell growth, function, and survival without the Irs2 branch of the insulin/insulin-like growth factor signaling cascade. |
| 3437 | 16170201 | The Irs2 branch of the insulin/insulin-like growth factor signaling cascade activates the phosphatidylinositol 3-kinase --> Akt --> Foxo1 cascade in many tissues, including hepatocytes and pancreatic beta-cells. |
| 3438 | 16170201 | To determine whether decreased Pten expression could restore beta-cell function and prevent diabetes in Irs2(-/-) mice, we generated wild type or Irs2 knock-out mice that were haploinsufficient for Pten (Irs2(-/-)::Pten(+/-)). |
| 3439 | 16170201 | Irs2(-/-) mice develop diabetes by 3 months of age as beta-cell mass declined progressively until insulin production was lost. |
| 3440 | 16170201 | Pten insufficiency increased peripheral insulin sensitivity in wild type and Irs2(-/-) mice and increased Akt and Foxo1 phosphorylation in the islets. |
| 3441 | 16170201 | Glucose tolerance improved in the Pten(+/-) mice, although beta-cell mass and circulating insulin levels decreased. |
| 3442 | 16170201 | Compared with Irs2(-/-) mice, the Irs2(-/-)::Pten(+/-) mice displayed nearly normal glucose tolerance and survived without diabetes, because normal but small islets produced sufficient insulin until the mice died of lymphoproliferative disease at 12 months age. |
| 3443 | 16170201 | Thus, steps to enhance phosphatidylinositol 3-kinase signaling can promote beta-cell growth, function, and survival without the Irs2 branch of the insulin/insulin-like growth factor signaling cascade. |
| 3444 | 16179727 | Insulin-sensitive protein kinases (atypical protein kinase C and protein kinase B/Akt): actions and defects in obesity and type II diabetes. |
| 3445 | 16179727 | Insulin regulates glucose transport by activating insulin receptor substrate-1 (IRS-1)-dependent phosphatidylinositol 3-kinase (PI3K) which, via increases in PI-3,4,5-triphosphate (PIP(3)), activates atypical protein kinase C (aPKC) and protein kinase B (PKB/Akt). |
| 3446 | 16179727 | Here, we review (i) the evidence that both aPKC and PKB are required for insulin-stimulated glucose transport, (ii) abnormalities in muscle aPKC/PKB activation seen in obesity and diabetes, and (iii) mechanisms for impaired aPKC activation in insulin-resistant conditions. |
| 3447 | 16179727 | In most cases, defective muscle aPKC/PKB activation reflects both impaired activation of IRS-1/PI3K, the upstream activator of aPKC and PKB in muscle and, in the case of aPKC, poor responsiveness to PIP(3), the lipid product of PI3K. |
| 3448 | 16179727 | Differently from muscle, aPKC activation in the liver is dependent on IRS-2/PI3K rather than IRS-1/PI3K and, surprisingly, the activation of IRS-2/PI3K and aPKC is conserved in high-fat feeding, obesity, and diabetes. |
| 3449 | 16179727 | On the other hand, the defective activation of IRS-1/PI3K and PKB, as seen in diabetic liver, undoubtedly and importantly contributes to increases in hepatic glucose output. |
| 3450 | 16179727 | Thus, the divergent activation of aPKC and PKB in the liver may explain why some hepatic actions of insulin (e.g., aPKC-dependent lipid synthesis) are increased while other actions (e.g., PKB-dependent glucose metabolism) are diminished. |
| 3451 | 16179727 | Insulin-sensitive protein kinases (atypical protein kinase C and protein kinase B/Akt): actions and defects in obesity and type II diabetes. |
| 3452 | 16179727 | Insulin regulates glucose transport by activating insulin receptor substrate-1 (IRS-1)-dependent phosphatidylinositol 3-kinase (PI3K) which, via increases in PI-3,4,5-triphosphate (PIP(3)), activates atypical protein kinase C (aPKC) and protein kinase B (PKB/Akt). |
| 3453 | 16179727 | Here, we review (i) the evidence that both aPKC and PKB are required for insulin-stimulated glucose transport, (ii) abnormalities in muscle aPKC/PKB activation seen in obesity and diabetes, and (iii) mechanisms for impaired aPKC activation in insulin-resistant conditions. |
| 3454 | 16179727 | In most cases, defective muscle aPKC/PKB activation reflects both impaired activation of IRS-1/PI3K, the upstream activator of aPKC and PKB in muscle and, in the case of aPKC, poor responsiveness to PIP(3), the lipid product of PI3K. |
| 3455 | 16179727 | Differently from muscle, aPKC activation in the liver is dependent on IRS-2/PI3K rather than IRS-1/PI3K and, surprisingly, the activation of IRS-2/PI3K and aPKC is conserved in high-fat feeding, obesity, and diabetes. |
| 3456 | 16179727 | On the other hand, the defective activation of IRS-1/PI3K and PKB, as seen in diabetic liver, undoubtedly and importantly contributes to increases in hepatic glucose output. |
| 3457 | 16179727 | Thus, the divergent activation of aPKC and PKB in the liver may explain why some hepatic actions of insulin (e.g., aPKC-dependent lipid synthesis) are increased while other actions (e.g., PKB-dependent glucose metabolism) are diminished. |
| 3458 | 16179727 | Insulin-sensitive protein kinases (atypical protein kinase C and protein kinase B/Akt): actions and defects in obesity and type II diabetes. |
| 3459 | 16179727 | Insulin regulates glucose transport by activating insulin receptor substrate-1 (IRS-1)-dependent phosphatidylinositol 3-kinase (PI3K) which, via increases in PI-3,4,5-triphosphate (PIP(3)), activates atypical protein kinase C (aPKC) and protein kinase B (PKB/Akt). |
| 3460 | 16179727 | Here, we review (i) the evidence that both aPKC and PKB are required for insulin-stimulated glucose transport, (ii) abnormalities in muscle aPKC/PKB activation seen in obesity and diabetes, and (iii) mechanisms for impaired aPKC activation in insulin-resistant conditions. |
| 3461 | 16179727 | In most cases, defective muscle aPKC/PKB activation reflects both impaired activation of IRS-1/PI3K, the upstream activator of aPKC and PKB in muscle and, in the case of aPKC, poor responsiveness to PIP(3), the lipid product of PI3K. |
| 3462 | 16179727 | Differently from muscle, aPKC activation in the liver is dependent on IRS-2/PI3K rather than IRS-1/PI3K and, surprisingly, the activation of IRS-2/PI3K and aPKC is conserved in high-fat feeding, obesity, and diabetes. |
| 3463 | 16179727 | On the other hand, the defective activation of IRS-1/PI3K and PKB, as seen in diabetic liver, undoubtedly and importantly contributes to increases in hepatic glucose output. |
| 3464 | 16179727 | Thus, the divergent activation of aPKC and PKB in the liver may explain why some hepatic actions of insulin (e.g., aPKC-dependent lipid synthesis) are increased while other actions (e.g., PKB-dependent glucose metabolism) are diminished. |
| 3465 | 16179727 | Insulin-sensitive protein kinases (atypical protein kinase C and protein kinase B/Akt): actions and defects in obesity and type II diabetes. |
| 3466 | 16179727 | Insulin regulates glucose transport by activating insulin receptor substrate-1 (IRS-1)-dependent phosphatidylinositol 3-kinase (PI3K) which, via increases in PI-3,4,5-triphosphate (PIP(3)), activates atypical protein kinase C (aPKC) and protein kinase B (PKB/Akt). |
| 3467 | 16179727 | Here, we review (i) the evidence that both aPKC and PKB are required for insulin-stimulated glucose transport, (ii) abnormalities in muscle aPKC/PKB activation seen in obesity and diabetes, and (iii) mechanisms for impaired aPKC activation in insulin-resistant conditions. |
| 3468 | 16179727 | In most cases, defective muscle aPKC/PKB activation reflects both impaired activation of IRS-1/PI3K, the upstream activator of aPKC and PKB in muscle and, in the case of aPKC, poor responsiveness to PIP(3), the lipid product of PI3K. |
| 3469 | 16179727 | Differently from muscle, aPKC activation in the liver is dependent on IRS-2/PI3K rather than IRS-1/PI3K and, surprisingly, the activation of IRS-2/PI3K and aPKC is conserved in high-fat feeding, obesity, and diabetes. |
| 3470 | 16179727 | On the other hand, the defective activation of IRS-1/PI3K and PKB, as seen in diabetic liver, undoubtedly and importantly contributes to increases in hepatic glucose output. |
| 3471 | 16179727 | Thus, the divergent activation of aPKC and PKB in the liver may explain why some hepatic actions of insulin (e.g., aPKC-dependent lipid synthesis) are increased while other actions (e.g., PKB-dependent glucose metabolism) are diminished. |
| 3472 | 16185843 | The scaffolding/adapter protein, Gab1, is a key signaling molecule for numerous stimuli including growth factors and G protein-coupled-receptors (GPCRs). |
| 3473 | 16185843 | HGF and EGF stimulated total Gab1 tyrosine phosphorylation (TyrP) and TyrP of Gab1 phospho-specific sites (Y307, Y627), but not other pancreatic growth factors, GI GPCRs (CCK, bombesin, carbachol, VIP, secretin), or agents directly activating PKC or increasing Ca2+. |
| 3474 | 16185843 | HGF-stimulated Y307 Gab1 TyrP differed in kinetics from total and Y627. |
| 3475 | 16185843 | In unstimulated cells>95% of Gab1 was cytosolic and HGF stimulated a 3-fold increase in membrane Gab1. |
| 3476 | 16185843 | HGF stimulated equal increases in pY307 and pY627 Gab1 in cytosol/membrane. |
| 3477 | 16185843 | HGF stimulated Gab1 association with c-Met, Grb2, SHP2, PI3K, Shc, Crk isoforms and CrkL, but not with PLCgamma1. |
| 3478 | 16185843 | These results demonstrate that only a subset of pancreatic growth factors (HGF/EGF) stimulates Gab1 signaling and no pancreatic hormones/neurotransmitters. |
| 3479 | 16186174 | Connective tissue growth factor (CTGF) expression in the brain is a downstream effector of insulin resistance- associated promotion of Alzheimer's disease beta-amyloid neuropathology. |
| 3480 | 16186174 | With this evidence we continued to explore the regulation of CTGF in postmortem AD brain tissue and found that CTGF expression correlated with the progression of AD clinical dementia and amyloid neuritic plaque (NP) neuropathology, but not neurofibrillary tangle (NFT) deposition. |
| 3481 | 16186174 | Consistent with this evidence, we also found that exposure of Tg2576 mice (a model AD-type amyloid neuropathology) to a diabetogenic diet that promotes IR results in a ~2-fold elevation in CTGF steady-state levels in the brain, coincident with a commensurate promotion of AD-type amyloid plaque burden. |
| 3482 | 16186174 | Finally, using in vitro cellular models of amyloid precursor protein (APP)-processing and Abeta generation/clearance, we confirmed that human recombinant (hr)CTGF may increase Abeta1-40 and Abeta1-42 peptide steady-state levels, possibly through a mechanism that involves gamma-secretase activation and decreased insulin-degrading enzyme (IDE) steady-state levels in a MAP kinase (MAPK)/ phosphatidylinositol 3-kinase (PI-3K)/protein kinase-B (AKT)1-dependent manner. |
| 3483 | 16187222 | We have recently shown that exposure to low levels of Abeta impairs BDNF trkB signal transduction, suppressing the Ras/ERK, and the PI3-K/Akt pathways but not the PLCgamma pathway. |
| 3484 | 16198623 | Xenobiotics-induced liver fibrosis was extremely diminished in ob/ob mice and Zucker (fa/fa) rats, an inborn leptin- and leptin receptor (Ob-R)-deficient animal, respectively. |
| 3485 | 16198623 | Further, leptin increased transforming growth factor (TGF)-beta mRNA in isolated sinusoidal endothelial cells and Kupffer cells, suggesting that leptin promotes hepatic fibrogenesis through up-regulation of TGF-beta in the liver. |
| 3486 | 16198623 | Moreover, leptin augmented PDGF-dependent proliferation of HSCs by enhancing downstream intracellular signaling pathways via mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3 kinase (PI3K)/Akt. |
| 3487 | 16240321 | Endothelin-1 (ET-1) disrupts insulin-regulated glucose transporter GLUT4 trafficking. |
| 3488 | 16240321 | Since the negative consequence of chronic ET-1 exposure appears to be independent of signal disturbance along the insulin receptor substrate-1/phosphatidylinositol (PI) 3-kinase (PI3K)/Akt-2 pathway of insulin action, we tested if ET-1 altered GLUT4 regulation engaged by osmotic shock, a PI3K-independent stimulus that mimics insulin action. |
| 3489 | 16240321 | Regulation of GLUT4 by hyperosmotic stress was impaired by ET-1. |
| 3490 | 16240321 | Because of the mutual disruption of both insulin- and hyperosmolarity-stimulated GLUT4 translocation, we tested whether shared signaling and/or key phosphatidylinositol 4,5-bisphosphate (PIP2)-regulated cytoskeletal events of GLUT4 trafficking were targets of ET-1. |
| 3491 | 16240321 | Both insulin and hyperosmotic stress signaling to Cbl were impaired by ET-1. |
| 3492 | 16240321 | These data show that ET-1-induced PIP2/actin disruption impairs GLUT4 trafficking elicited by insulin and hyperosmolarity. |
| 3493 | 16240321 | In addition to showing for the first time the important role of PIP2-regulated cytoskeletal events in GLUT4 regulation by stimuli other than insulin, these studies reveal a novel function of PIP2/actin structure in signal transduction. |
| 3494 | 16243841 | Resistin-like molecule beta activates MAPKs, suppresses insulin signaling in hepatocytes, and induces diabetes, hyperlipidemia, and fatty liver in transgenic mice on a high fat diet. |
| 3495 | 16243841 | Resistin and resistin-like molecules (RELMs) are a family of proteins reportedly related to insulin resistance and inflammation. |
| 3496 | 16243841 | Because the serum concentration and intestinal expression level of RELMbeta were elevated in insulin-resistant rodent models, in this study we investigated the effect of RELMbeta on insulin signaling and metabolism using transgenic mice and primary cultured hepatocytes. |
| 3497 | 16243841 | In addition, the expression levels of IRS-1 and IRS-2 proteins as well as the degrees of insulin-induced phosphatidylinositol 3-kinase and Akt activations were attenuated in RELMbeta transgenic mice. |
| 3498 | 16243841 | Similar down-regulations of IRS-1 and IRS-2 proteins were observed in primary cultured hepatocytes chronically treated (for 24 h) with RELMbeta, suggesting the insulin resistance-inducing effect of RELMbeta to be direct. |
| 3499 | 16243841 | Furthermore, it was shown that RELMbeta acutely and markedly activates ERK and p38, while weakly activating JNK, in primary cultured hepatocytes. |
| 3500 | 16243841 | This increased basal p38 phosphorylation level was also observed in the livers of RELMbeta transgenic mice. |
| 3501 | 16243841 | In conclusion, RELMbeta, a gut-derived hormone, impairs insulin signaling probably via the activations of classic MAPKs, and increased expression of RELMbeta may be involved in the pathogenesis of glucose intolerance and hyperlipidemia in some insulin-resistant models. |
| 3502 | 16243841 | Thus, RELMbeta is a potentially useful marker for assessing insulin resistance and may also be a target for future novel anti-diabetic agents. |
| 3503 | 16249255 | Increased collagen content in insulin-resistant skeletal muscle. |
| 3504 | 16249255 | Because evidence indicates that lipid oversupply can produce abnormalities in extracellular matrix composition and matrix changes can affect the function of mitochondria, the present study was undertaken to determine whether muscle from insulin-resistant, nondiabetic obese subjects and patients with type 2 diabetes mellitus had increased collagen content. |
| 3505 | 16249255 | Compared with lean control subjects, obese and type 2 diabetic subjects had reduced muscle glucose uptake (P<0.01) and decreased insulin stimulation of tyrosine phosphorylation of insulin receptor substrate-1 and its ability to associate with phosphatidylinositol 3-kinase (P<0.01 and P<.05). |
| 3506 | 16293713 | Identification of the insulin signaling cascade in the regulation of alpha-class glutathione S-transferase expression in primary cultured rat hepatocytes. |
| 3507 | 16293713 | We reported previously that insulin elevated alpha-class glutathione S-transferase (GSTs) protein levels in primary cultured rat hepatocytes (Kim et al., 2003b). |
| 3508 | 16293713 | In contrast, glucagon down-regulated alpha- and pi-class GST expression, and mechanistic research implicated cAMP and protein kinase A in this process (Kim et al., 2003b). |
| 3509 | 16293713 | The present study examines the signaling pathways involved in the regulation of alpha-class GST in response to insulin in primary cultured rat hepatocytes. |
| 3510 | 16293713 | Protein levels of GSTA1/2 and GSTA3/5 and activity of GST toward 7-chloro-4-nitrobenzo-2-oxa-1,3-diazole (NBD) were increased in an insulin concentration-dependent manner. |
| 3511 | 16293713 | Treatment of cells with the phosphatidylinositol 3-kinase (PI3K) inhibitors wortmannin and LY294002 [2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one] or rapamycin, an inhibitor of mammalian target of rapamycin and ribosomal p70 S6 kinase (p70S6K) phosphorylation, or with an adenovirus containing green fluorescent protein and a dominant-negative and kinase-dead Akt, effectively inhibited the insulin-mediated increase in alpha-class GST expression and GST activity toward NBD. |
| 3512 | 16293713 | In contrast, PD98059 (2'-amino-3'-methoxyflavone), an inhibitor of mitogen-activated protein kinase kinase, SP600125 (1,9-pyrazoloanthrone), an inhibitor of c-Jun N-terminal kinase, SB203580 [4-(4-fluorophenyl)-2-(4-methylsulfinylphenyl)-5-(4-pyridyl)1H-imadazole], an inhibitor of p38 mitogen-activated protein kinase, or bisindolylmaleimide, a broad spectrum inhibitor of protein kinase C, did not inhibit the insulin-mediated increase in alpha-class GST protein levels in hepatocytes. |
| 3513 | 16293713 | These results show that PI3K/Akt/p70S6K signaling is active in the insulin-mediated up-regulation of the antioxidant defense system and that low insulin levels, as encountered in diabetes, potentially increase the susceptibility of hepatocytes to xenobiotic-mediated and/or oxidative stress-mediated damage. |
| 3514 | 16293713 | Identification of the insulin signaling cascade in the regulation of alpha-class glutathione S-transferase expression in primary cultured rat hepatocytes. |
| 3515 | 16293713 | We reported previously that insulin elevated alpha-class glutathione S-transferase (GSTs) protein levels in primary cultured rat hepatocytes (Kim et al., 2003b). |
| 3516 | 16293713 | In contrast, glucagon down-regulated alpha- and pi-class GST expression, and mechanistic research implicated cAMP and protein kinase A in this process (Kim et al., 2003b). |
| 3517 | 16293713 | The present study examines the signaling pathways involved in the regulation of alpha-class GST in response to insulin in primary cultured rat hepatocytes. |
| 3518 | 16293713 | Protein levels of GSTA1/2 and GSTA3/5 and activity of GST toward 7-chloro-4-nitrobenzo-2-oxa-1,3-diazole (NBD) were increased in an insulin concentration-dependent manner. |
| 3519 | 16293713 | Treatment of cells with the phosphatidylinositol 3-kinase (PI3K) inhibitors wortmannin and LY294002 [2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one] or rapamycin, an inhibitor of mammalian target of rapamycin and ribosomal p70 S6 kinase (p70S6K) phosphorylation, or with an adenovirus containing green fluorescent protein and a dominant-negative and kinase-dead Akt, effectively inhibited the insulin-mediated increase in alpha-class GST expression and GST activity toward NBD. |
| 3520 | 16293713 | In contrast, PD98059 (2'-amino-3'-methoxyflavone), an inhibitor of mitogen-activated protein kinase kinase, SP600125 (1,9-pyrazoloanthrone), an inhibitor of c-Jun N-terminal kinase, SB203580 [4-(4-fluorophenyl)-2-(4-methylsulfinylphenyl)-5-(4-pyridyl)1H-imadazole], an inhibitor of p38 mitogen-activated protein kinase, or bisindolylmaleimide, a broad spectrum inhibitor of protein kinase C, did not inhibit the insulin-mediated increase in alpha-class GST protein levels in hepatocytes. |
| 3521 | 16293713 | These results show that PI3K/Akt/p70S6K signaling is active in the insulin-mediated up-regulation of the antioxidant defense system and that low insulin levels, as encountered in diabetes, potentially increase the susceptibility of hepatocytes to xenobiotic-mediated and/or oxidative stress-mediated damage. |
| 3522 | 16301821 | This was followed by the inhibition of insulin-stimulated IRbeta tyrosine phosphorylation that consequently resulted inhibition of insulin receptor substrate 1 (IRS 1) and IRS 1 associated phosphatidylinositol-3 kinase (PI3 Kinase), phosphoinositide dependent kinase-1 (PDK 1) phosphorylation. |
| 3523 | 16301821 | PDK 1 dependent phosphorylation of PKCzeta and Akt/PKB were also inhibited by palmitate. |
| 3524 | 16306364 | Skeletal muscle insulin signaling defects downstream of phosphatidylinositol 3-kinase at the level of Akt are associated with impaired nonoxidative glucose disposal in HIV lipodystrophy. |
| 3525 | 16306364 | Insulin-stimulated Akt Ser473 and Akt Thr308 phosphorylation was decreased in LIPO patients (P < 0.05), whereas insulin receptor substrate-1-associated phosphatidylinositol (PI) 3-kinase activity increased significantly (P < 0.001) and similarly (NS) in both groups during clamp. |
| 3526 | 16306364 | Thus, low glycogen synthase activity explained impaired NOGM(ins) in HIV lipodystrophy, and insulin signaling defects were downstream of PI 3-kinase at the level of Akt. |
| 3527 | 16306807 | Pioglitazone mimics preconditioning in the isolated perfused rat heart: a role for the prosurvival kinases PI3K and P42/44MAPK. |
| 3528 | 16306807 | Ischemic preconditioning, the most powerful protection against infarction, activates PI3Kinase (PI3K)/AKT and P42/44MAPK. |
| 3529 | 16306807 | Additional groups underwent the same protocol but with either PI3K inhibitors (15 microM LY294002 or 100 nM wortmannin) or P42/44MAPK inhibitors (10 microM U0126 or 10 microM PD98059) given either during stabilization or at reperfusion. |
| 3530 | 16306807 | This protection was abolished by PI3K inhibitors (pioglitazone+LY294002 46.5 +/- 5.0, pioglitazone + wortmannin 48.8 +/- 4.6 versus pioglitazone alone 25.4 +/- 3.1; P < or = 0.05) but not by P42/44MAPK inhibitors (pioglitazone+U0126 30.7 +/- 5.7, pioglitazone + PD98059 28.5 +/- 6.3 versus pioglitazone alone 25.4 +/- 3.1; P < or = 0.05) given in stabilization. |
| 3531 | 16306807 | This protection appears to involve PI3K and P42/44MAPK. |
| 3532 | 16306807 | Pioglitazone mimics preconditioning in the isolated perfused rat heart: a role for the prosurvival kinases PI3K and P42/44MAPK. |
| 3533 | 16306807 | Ischemic preconditioning, the most powerful protection against infarction, activates PI3Kinase (PI3K)/AKT and P42/44MAPK. |
| 3534 | 16306807 | Additional groups underwent the same protocol but with either PI3K inhibitors (15 microM LY294002 or 100 nM wortmannin) or P42/44MAPK inhibitors (10 microM U0126 or 10 microM PD98059) given either during stabilization or at reperfusion. |
| 3535 | 16306807 | This protection was abolished by PI3K inhibitors (pioglitazone+LY294002 46.5 +/- 5.0, pioglitazone + wortmannin 48.8 +/- 4.6 versus pioglitazone alone 25.4 +/- 3.1; P < or = 0.05) but not by P42/44MAPK inhibitors (pioglitazone+U0126 30.7 +/- 5.7, pioglitazone + PD98059 28.5 +/- 6.3 versus pioglitazone alone 25.4 +/- 3.1; P < or = 0.05) given in stabilization. |
| 3536 | 16306807 | This protection appears to involve PI3K and P42/44MAPK. |
| 3537 | 16306807 | Pioglitazone mimics preconditioning in the isolated perfused rat heart: a role for the prosurvival kinases PI3K and P42/44MAPK. |
| 3538 | 16306807 | Ischemic preconditioning, the most powerful protection against infarction, activates PI3Kinase (PI3K)/AKT and P42/44MAPK. |
| 3539 | 16306807 | Additional groups underwent the same protocol but with either PI3K inhibitors (15 microM LY294002 or 100 nM wortmannin) or P42/44MAPK inhibitors (10 microM U0126 or 10 microM PD98059) given either during stabilization or at reperfusion. |
| 3540 | 16306807 | This protection was abolished by PI3K inhibitors (pioglitazone+LY294002 46.5 +/- 5.0, pioglitazone + wortmannin 48.8 +/- 4.6 versus pioglitazone alone 25.4 +/- 3.1; P < or = 0.05) but not by P42/44MAPK inhibitors (pioglitazone+U0126 30.7 +/- 5.7, pioglitazone + PD98059 28.5 +/- 6.3 versus pioglitazone alone 25.4 +/- 3.1; P < or = 0.05) given in stabilization. |
| 3541 | 16306807 | This protection appears to involve PI3K and P42/44MAPK. |
| 3542 | 16306807 | Pioglitazone mimics preconditioning in the isolated perfused rat heart: a role for the prosurvival kinases PI3K and P42/44MAPK. |
| 3543 | 16306807 | Ischemic preconditioning, the most powerful protection against infarction, activates PI3Kinase (PI3K)/AKT and P42/44MAPK. |
| 3544 | 16306807 | Additional groups underwent the same protocol but with either PI3K inhibitors (15 microM LY294002 or 100 nM wortmannin) or P42/44MAPK inhibitors (10 microM U0126 or 10 microM PD98059) given either during stabilization or at reperfusion. |
| 3545 | 16306807 | This protection was abolished by PI3K inhibitors (pioglitazone+LY294002 46.5 +/- 5.0, pioglitazone + wortmannin 48.8 +/- 4.6 versus pioglitazone alone 25.4 +/- 3.1; P < or = 0.05) but not by P42/44MAPK inhibitors (pioglitazone+U0126 30.7 +/- 5.7, pioglitazone + PD98059 28.5 +/- 6.3 versus pioglitazone alone 25.4 +/- 3.1; P < or = 0.05) given in stabilization. |
| 3546 | 16306807 | This protection appears to involve PI3K and P42/44MAPK. |
| 3547 | 16306807 | Pioglitazone mimics preconditioning in the isolated perfused rat heart: a role for the prosurvival kinases PI3K and P42/44MAPK. |
| 3548 | 16306807 | Ischemic preconditioning, the most powerful protection against infarction, activates PI3Kinase (PI3K)/AKT and P42/44MAPK. |
| 3549 | 16306807 | Additional groups underwent the same protocol but with either PI3K inhibitors (15 microM LY294002 or 100 nM wortmannin) or P42/44MAPK inhibitors (10 microM U0126 or 10 microM PD98059) given either during stabilization or at reperfusion. |
| 3550 | 16306807 | This protection was abolished by PI3K inhibitors (pioglitazone+LY294002 46.5 +/- 5.0, pioglitazone + wortmannin 48.8 +/- 4.6 versus pioglitazone alone 25.4 +/- 3.1; P < or = 0.05) but not by P42/44MAPK inhibitors (pioglitazone+U0126 30.7 +/- 5.7, pioglitazone + PD98059 28.5 +/- 6.3 versus pioglitazone alone 25.4 +/- 3.1; P < or = 0.05) given in stabilization. |
| 3551 | 16306807 | This protection appears to involve PI3K and P42/44MAPK. |
| 3552 | 16311104 | Continually high insulin levels impair Akt phosphorylation and glucose transport in human myoblasts. |
| 3553 | 16311104 | Glucose transport, insulin receptor (IR), and IR substrate 1 (IRS1) phosphorylation, phosphatidylinositol 3'-kinase (PI3K) activity, as well as Akt-Ser473 phosphorylation have been investigated at the end of the incubation period and after a further short-term insulin stimulation. |
| 3554 | 16311104 | At the end of the incubation period, IR, IRS1, p85/PI3K, Akt, and GLUT4 protein expression levels were similar in both culture conditions. |
| 3555 | 16311104 | IR binding was down-regulated in SkMC-H (P < .01), but IR and IRS1 tyrosine phosphorylation and PI3K activity were significantly higher (P < .01) in SkMC-H than SkMC-L. |
| 3556 | 16311104 | Despite increased PI3K activation, Akt-Ser473 phosphorylation was similar in SkMC-L and SkMC-H. |
| 3557 | 16311104 | After a short-term insulin stimulation (10 nmol/L insulin for 10 minutes), IR and IRS1 tyrosine phosphorylation, PI3K activation, and Akt-Ser473 phosphorylation significantly increased (P < .01 and P < .05 for Akt) in SkMC-L but not in SkMC-H. |
| 3558 | 16311104 | Moreover, in the SkMC-H, insulin stimulation was associated with the inhibition of IRS1 tyrosine dephosphorylation (P < .05). |
| 3559 | 16311104 | In summary, continuous exposure of cultured myoblasts to high insulin levels induces a persistent up-regulation of IR, IRS1, and PI3K activity associated with the demodulation of insulin signaling. |
| 3560 | 16311104 | Moreover, the impairment of the insulin-signaling steps between PI3K and Akt is concomitant with the desensitization of glucose transport. |
| 3561 | 16311104 | Continually high insulin levels impair Akt phosphorylation and glucose transport in human myoblasts. |
| 3562 | 16311104 | Glucose transport, insulin receptor (IR), and IR substrate 1 (IRS1) phosphorylation, phosphatidylinositol 3'-kinase (PI3K) activity, as well as Akt-Ser473 phosphorylation have been investigated at the end of the incubation period and after a further short-term insulin stimulation. |
| 3563 | 16311104 | At the end of the incubation period, IR, IRS1, p85/PI3K, Akt, and GLUT4 protein expression levels were similar in both culture conditions. |
| 3564 | 16311104 | IR binding was down-regulated in SkMC-H (P < .01), but IR and IRS1 tyrosine phosphorylation and PI3K activity were significantly higher (P < .01) in SkMC-H than SkMC-L. |
| 3565 | 16311104 | Despite increased PI3K activation, Akt-Ser473 phosphorylation was similar in SkMC-L and SkMC-H. |
| 3566 | 16311104 | After a short-term insulin stimulation (10 nmol/L insulin for 10 minutes), IR and IRS1 tyrosine phosphorylation, PI3K activation, and Akt-Ser473 phosphorylation significantly increased (P < .01 and P < .05 for Akt) in SkMC-L but not in SkMC-H. |
| 3567 | 16311104 | Moreover, in the SkMC-H, insulin stimulation was associated with the inhibition of IRS1 tyrosine dephosphorylation (P < .05). |
| 3568 | 16311104 | In summary, continuous exposure of cultured myoblasts to high insulin levels induces a persistent up-regulation of IR, IRS1, and PI3K activity associated with the demodulation of insulin signaling. |
| 3569 | 16311104 | Moreover, the impairment of the insulin-signaling steps between PI3K and Akt is concomitant with the desensitization of glucose transport. |
| 3570 | 16311104 | Continually high insulin levels impair Akt phosphorylation and glucose transport in human myoblasts. |
| 3571 | 16311104 | Glucose transport, insulin receptor (IR), and IR substrate 1 (IRS1) phosphorylation, phosphatidylinositol 3'-kinase (PI3K) activity, as well as Akt-Ser473 phosphorylation have been investigated at the end of the incubation period and after a further short-term insulin stimulation. |
| 3572 | 16311104 | At the end of the incubation period, IR, IRS1, p85/PI3K, Akt, and GLUT4 protein expression levels were similar in both culture conditions. |
| 3573 | 16311104 | IR binding was down-regulated in SkMC-H (P < .01), but IR and IRS1 tyrosine phosphorylation and PI3K activity were significantly higher (P < .01) in SkMC-H than SkMC-L. |
| 3574 | 16311104 | Despite increased PI3K activation, Akt-Ser473 phosphorylation was similar in SkMC-L and SkMC-H. |
| 3575 | 16311104 | After a short-term insulin stimulation (10 nmol/L insulin for 10 minutes), IR and IRS1 tyrosine phosphorylation, PI3K activation, and Akt-Ser473 phosphorylation significantly increased (P < .01 and P < .05 for Akt) in SkMC-L but not in SkMC-H. |
| 3576 | 16311104 | Moreover, in the SkMC-H, insulin stimulation was associated with the inhibition of IRS1 tyrosine dephosphorylation (P < .05). |
| 3577 | 16311104 | In summary, continuous exposure of cultured myoblasts to high insulin levels induces a persistent up-regulation of IR, IRS1, and PI3K activity associated with the demodulation of insulin signaling. |
| 3578 | 16311104 | Moreover, the impairment of the insulin-signaling steps between PI3K and Akt is concomitant with the desensitization of glucose transport. |
| 3579 | 16311104 | Continually high insulin levels impair Akt phosphorylation and glucose transport in human myoblasts. |
| 3580 | 16311104 | Glucose transport, insulin receptor (IR), and IR substrate 1 (IRS1) phosphorylation, phosphatidylinositol 3'-kinase (PI3K) activity, as well as Akt-Ser473 phosphorylation have been investigated at the end of the incubation period and after a further short-term insulin stimulation. |
| 3581 | 16311104 | At the end of the incubation period, IR, IRS1, p85/PI3K, Akt, and GLUT4 protein expression levels were similar in both culture conditions. |
| 3582 | 16311104 | IR binding was down-regulated in SkMC-H (P < .01), but IR and IRS1 tyrosine phosphorylation and PI3K activity were significantly higher (P < .01) in SkMC-H than SkMC-L. |
| 3583 | 16311104 | Despite increased PI3K activation, Akt-Ser473 phosphorylation was similar in SkMC-L and SkMC-H. |
| 3584 | 16311104 | After a short-term insulin stimulation (10 nmol/L insulin for 10 minutes), IR and IRS1 tyrosine phosphorylation, PI3K activation, and Akt-Ser473 phosphorylation significantly increased (P < .01 and P < .05 for Akt) in SkMC-L but not in SkMC-H. |
| 3585 | 16311104 | Moreover, in the SkMC-H, insulin stimulation was associated with the inhibition of IRS1 tyrosine dephosphorylation (P < .05). |
| 3586 | 16311104 | In summary, continuous exposure of cultured myoblasts to high insulin levels induces a persistent up-regulation of IR, IRS1, and PI3K activity associated with the demodulation of insulin signaling. |
| 3587 | 16311104 | Moreover, the impairment of the insulin-signaling steps between PI3K and Akt is concomitant with the desensitization of glucose transport. |
| 3588 | 16311104 | Continually high insulin levels impair Akt phosphorylation and glucose transport in human myoblasts. |
| 3589 | 16311104 | Glucose transport, insulin receptor (IR), and IR substrate 1 (IRS1) phosphorylation, phosphatidylinositol 3'-kinase (PI3K) activity, as well as Akt-Ser473 phosphorylation have been investigated at the end of the incubation period and after a further short-term insulin stimulation. |
| 3590 | 16311104 | At the end of the incubation period, IR, IRS1, p85/PI3K, Akt, and GLUT4 protein expression levels were similar in both culture conditions. |
| 3591 | 16311104 | IR binding was down-regulated in SkMC-H (P < .01), but IR and IRS1 tyrosine phosphorylation and PI3K activity were significantly higher (P < .01) in SkMC-H than SkMC-L. |
| 3592 | 16311104 | Despite increased PI3K activation, Akt-Ser473 phosphorylation was similar in SkMC-L and SkMC-H. |
| 3593 | 16311104 | After a short-term insulin stimulation (10 nmol/L insulin for 10 minutes), IR and IRS1 tyrosine phosphorylation, PI3K activation, and Akt-Ser473 phosphorylation significantly increased (P < .01 and P < .05 for Akt) in SkMC-L but not in SkMC-H. |
| 3594 | 16311104 | Moreover, in the SkMC-H, insulin stimulation was associated with the inhibition of IRS1 tyrosine dephosphorylation (P < .05). |
| 3595 | 16311104 | In summary, continuous exposure of cultured myoblasts to high insulin levels induces a persistent up-regulation of IR, IRS1, and PI3K activity associated with the demodulation of insulin signaling. |
| 3596 | 16311104 | Moreover, the impairment of the insulin-signaling steps between PI3K and Akt is concomitant with the desensitization of glucose transport. |
| 3597 | 16311104 | Continually high insulin levels impair Akt phosphorylation and glucose transport in human myoblasts. |
| 3598 | 16311104 | Glucose transport, insulin receptor (IR), and IR substrate 1 (IRS1) phosphorylation, phosphatidylinositol 3'-kinase (PI3K) activity, as well as Akt-Ser473 phosphorylation have been investigated at the end of the incubation period and after a further short-term insulin stimulation. |
| 3599 | 16311104 | At the end of the incubation period, IR, IRS1, p85/PI3K, Akt, and GLUT4 protein expression levels were similar in both culture conditions. |
| 3600 | 16311104 | IR binding was down-regulated in SkMC-H (P < .01), but IR and IRS1 tyrosine phosphorylation and PI3K activity were significantly higher (P < .01) in SkMC-H than SkMC-L. |
| 3601 | 16311104 | Despite increased PI3K activation, Akt-Ser473 phosphorylation was similar in SkMC-L and SkMC-H. |
| 3602 | 16311104 | After a short-term insulin stimulation (10 nmol/L insulin for 10 minutes), IR and IRS1 tyrosine phosphorylation, PI3K activation, and Akt-Ser473 phosphorylation significantly increased (P < .01 and P < .05 for Akt) in SkMC-L but not in SkMC-H. |
| 3603 | 16311104 | Moreover, in the SkMC-H, insulin stimulation was associated with the inhibition of IRS1 tyrosine dephosphorylation (P < .05). |
| 3604 | 16311104 | In summary, continuous exposure of cultured myoblasts to high insulin levels induces a persistent up-regulation of IR, IRS1, and PI3K activity associated with the demodulation of insulin signaling. |
| 3605 | 16311104 | Moreover, the impairment of the insulin-signaling steps between PI3K and Akt is concomitant with the desensitization of glucose transport. |
| 3606 | 16311104 | Continually high insulin levels impair Akt phosphorylation and glucose transport in human myoblasts. |
| 3607 | 16311104 | Glucose transport, insulin receptor (IR), and IR substrate 1 (IRS1) phosphorylation, phosphatidylinositol 3'-kinase (PI3K) activity, as well as Akt-Ser473 phosphorylation have been investigated at the end of the incubation period and after a further short-term insulin stimulation. |
| 3608 | 16311104 | At the end of the incubation period, IR, IRS1, p85/PI3K, Akt, and GLUT4 protein expression levels were similar in both culture conditions. |
| 3609 | 16311104 | IR binding was down-regulated in SkMC-H (P < .01), but IR and IRS1 tyrosine phosphorylation and PI3K activity were significantly higher (P < .01) in SkMC-H than SkMC-L. |
| 3610 | 16311104 | Despite increased PI3K activation, Akt-Ser473 phosphorylation was similar in SkMC-L and SkMC-H. |
| 3611 | 16311104 | After a short-term insulin stimulation (10 nmol/L insulin for 10 minutes), IR and IRS1 tyrosine phosphorylation, PI3K activation, and Akt-Ser473 phosphorylation significantly increased (P < .01 and P < .05 for Akt) in SkMC-L but not in SkMC-H. |
| 3612 | 16311104 | Moreover, in the SkMC-H, insulin stimulation was associated with the inhibition of IRS1 tyrosine dephosphorylation (P < .05). |
| 3613 | 16311104 | In summary, continuous exposure of cultured myoblasts to high insulin levels induces a persistent up-regulation of IR, IRS1, and PI3K activity associated with the demodulation of insulin signaling. |
| 3614 | 16311104 | Moreover, the impairment of the insulin-signaling steps between PI3K and Akt is concomitant with the desensitization of glucose transport. |
| 3615 | 16313516 | Inhibitors of protein kinase C (PKC) and of Src kinases, including p59Fyn, blocked the effect of recPrP on axon elongation, while inhibitors of phosphatidylinositol 3-kinase showed a partial inhibition, suggesting that signaling cascades involving these kinases are candidates for transduction of recPrP-mediated signals. |
| 3616 | 16319959 | Insulin promotes glucose uptake into muscle and adipose tissues through glucose transporter 4 (GLUT4). |
| 3617 | 16319959 | The coordinated action of phosphatidylinositol 3-kinase effectors, protein kinase Akt, atypical protein kinase C (aPKC) and Akt substrate of 160-kDa (AS160), regulates the GLUT4 cycle by affecting its translocation, fusion with the plasma membrane, internalization and sorting. |
| 3618 | 16319959 | We review the evidence that supports such cycling, evaluate current models proposing static or dynamic retention, and highlight how distinct steps of GLUT4 transport are regulated by insulin signals. |
| 3619 | 16319959 | In particular, fusion seems to be regulated by aPKC (via munc18) and Akt (via syntaxin4-interacting protein (synip)). |
| 3620 | 16319959 | AS160 participates in GLUT4 intracellular retention, and possibly fusion, through candidate ras-related GTP-binding protein (Rab)2, Rab8, Rab10 and/or Rab14. |
| 3621 | 16319959 | The localization of the insulin-sensitive GLUT4 compartment and the precise target of insulin-derived signals remain open for future investigation. |
| 3622 | 16337244 | Inhibition of FFA release by these vanadyl compounds was found to be reversed by the addition of inhibitors, typically by cytochalasin B (glucose transporter 4 (GLUT4) inhibitor), cilostamide (phosphodiesterase inhibitor), HNMPA-(AM)3 (tyrosine kinase inhibitor), and wortmannin (PI3-k inhibitor), indicating that these compounds affect primarily GLUT4 and phosphodiesterase, as named "ensemble mechanism". |
| 3623 | 16339278 | Chromium activates glucose transporter 4 trafficking and enhances insulin-stimulated glucose transport in 3T3-L1 adipocytes via a cholesterol-dependent mechanism. |
| 3624 | 16339278 | Concomitant with an increase in GLUT4 at the plasma membrane, insulin-stimulated glucose transport was enhanced by chromium treatment. |
| 3625 | 16339278 | Regulation of GLUT4 translocation by chromium did not involve known insulin signaling proteins such as the insulin receptor, insulin receptor substrate-1, phosphatidylinositol 3-kinase, and Akt. |
| 3626 | 16339278 | Interestingly, cholesterol add-back to the plasma membrane prevented the beneficial effect of chromium on both GLUT4 mobilization and insulin-stimulated glucose transport. |
| 3627 | 16339278 | Together, these data reveal a novel mechanism by which chromium may enhance GLUT4 trafficking and insulin-stimulated glucose transport. |
| 3628 | 16344371 | Peroxisome proliferator-activated receptor gamma regulates angiotensin II-stimulated phosphatidylinositol 3-kinase and mitogen-activated protein kinase in blood vessels in vivo. |
| 3629 | 16344371 | Angiotensin (Ang) II is implicated in hypertension, vascular remodeling, and insulin resistance. |
| 3630 | 16344371 | Peroxisome proliferator-activated receptor (PPAR) gamma activators increase insulin sensitivity and improve Ang II-induced vascular remodeling. |
| 3631 | 16344371 | We evaluated the effects of the PPAR-gamma activator rosiglitazone on Ang II signaling in aorta and mesenteric arteries. |
| 3632 | 16344371 | Akt activity was increased by Ang II and returned to basal levels under rosiglitazone in both vascular beds. |
| 3633 | 16344371 | However, Ang II-induced extracellular signal-regulated kinase 1/2 activity increased in aorta but not in mesenteric vessels (P<0.001), where 4E-binding protein 1 activity was significantly increased by Ang II and inhibited by PPAR-gamma activation. |
| 3634 | 16344371 | In response to Ang II, Src homology (SH) 2-containing inositol phosphatase 2 activity was increased (P<0.05) in both vascular beds. |
| 3635 | 16344371 | In conclusion, PPAR-gamma activator rosiglitazone attenuated Ang II-induced blood pressure elevation and intracellular signaling on aorta and mesenteric vessels. |
| 3636 | 16344371 | There was differential inhibition of Ang II type 1 receptor receptors/phosphatidylinositol 3-kinase/Akt and extracellular signal-regulated kinase 1/2 in both vessels. |
| 3637 | 16344371 | Peroxisome proliferator-activated receptor gamma regulates angiotensin II-stimulated phosphatidylinositol 3-kinase and mitogen-activated protein kinase in blood vessels in vivo. |
| 3638 | 16344371 | Angiotensin (Ang) II is implicated in hypertension, vascular remodeling, and insulin resistance. |
| 3639 | 16344371 | Peroxisome proliferator-activated receptor (PPAR) gamma activators increase insulin sensitivity and improve Ang II-induced vascular remodeling. |
| 3640 | 16344371 | We evaluated the effects of the PPAR-gamma activator rosiglitazone on Ang II signaling in aorta and mesenteric arteries. |
| 3641 | 16344371 | Akt activity was increased by Ang II and returned to basal levels under rosiglitazone in both vascular beds. |
| 3642 | 16344371 | However, Ang II-induced extracellular signal-regulated kinase 1/2 activity increased in aorta but not in mesenteric vessels (P<0.001), where 4E-binding protein 1 activity was significantly increased by Ang II and inhibited by PPAR-gamma activation. |
| 3643 | 16344371 | In response to Ang II, Src homology (SH) 2-containing inositol phosphatase 2 activity was increased (P<0.05) in both vascular beds. |
| 3644 | 16344371 | In conclusion, PPAR-gamma activator rosiglitazone attenuated Ang II-induced blood pressure elevation and intracellular signaling on aorta and mesenteric vessels. |
| 3645 | 16344371 | There was differential inhibition of Ang II type 1 receptor receptors/phosphatidylinositol 3-kinase/Akt and extracellular signal-regulated kinase 1/2 in both vessels. |
| 3646 | 16354680 | Nutrients suppress phosphatidylinositol 3-kinase/Akt signaling via raptor-dependent mTOR-mediated insulin receptor substrate 1 phosphorylation. |
| 3647 | 16354680 | Here, we demonstrate that nutrients suppress phosphatidylinositol 3 (PI3)-kinase/Akt signaling via Raptor-dependent mTOR (mammalian target of rapamycin)-mediated phosphorylation of insulin receptor substrate 1 (IRS-1). |
| 3648 | 16354680 | These serines lie close to the Y(632)MPM motif that is implicated in the binding of p85alpha/p110alpha PI3-kinase to IRS-1 upon insulin stimulation. |
| 3649 | 16354680 | Phosphomimicking mutations of these serines block insulin-stimulated activation of IRS-1-associated PI3-kinase. |
| 3650 | 16354680 | Knockdown of Raptor as well as activators of the LKB1/AMPK pathway, such as the widely used antidiabetic compound metformin, suppress IRS-1 Ser636/639 phosphorylation and reverse mTOR-mediated inhibition on PI3-kinase/Akt signaling. |
| 3651 | 16354680 | Thus, diabetes-related hyperglycemia hyperactivates the mTOR pathway and may lead to insulin resistance due to suppression of IRS-1-dependent PI3-kinase/Akt signaling. |
| 3652 | 16354680 | Nutrients suppress phosphatidylinositol 3-kinase/Akt signaling via raptor-dependent mTOR-mediated insulin receptor substrate 1 phosphorylation. |
| 3653 | 16354680 | Here, we demonstrate that nutrients suppress phosphatidylinositol 3 (PI3)-kinase/Akt signaling via Raptor-dependent mTOR (mammalian target of rapamycin)-mediated phosphorylation of insulin receptor substrate 1 (IRS-1). |
| 3654 | 16354680 | These serines lie close to the Y(632)MPM motif that is implicated in the binding of p85alpha/p110alpha PI3-kinase to IRS-1 upon insulin stimulation. |
| 3655 | 16354680 | Phosphomimicking mutations of these serines block insulin-stimulated activation of IRS-1-associated PI3-kinase. |
| 3656 | 16354680 | Knockdown of Raptor as well as activators of the LKB1/AMPK pathway, such as the widely used antidiabetic compound metformin, suppress IRS-1 Ser636/639 phosphorylation and reverse mTOR-mediated inhibition on PI3-kinase/Akt signaling. |
| 3657 | 16354680 | Thus, diabetes-related hyperglycemia hyperactivates the mTOR pathway and may lead to insulin resistance due to suppression of IRS-1-dependent PI3-kinase/Akt signaling. |
| 3658 | 16364246 | Insulin increased transcription of the PPARgamma2 gene via phosphatidylinositol 3-kinase activation. |
| 3659 | 16364246 | Also aP2 mRNA expression was induced by rosiglitazone to a higher degree in the presence of insulin, while acyl-CoA oxidase was increased independently of insulin. |
| 3660 | 16373398 | Dehydroepiandrosterone mimics acute actions of insulin to stimulate production of both nitric oxide and endothelin 1 via distinct phosphatidylinositol 3-kinase- and mitogen-activated protein kinase-dependent pathways in vascular endothelium. |
| 3661 | 16373398 | Because DHEA may augment insulin sensitivity, we hypothesized that DHEA mimics vascular actions of insulin to acutely activate signaling pathways in endothelium-mediating production of nitric oxide (NO) and endothelin 1 (ET-1). |
| 3662 | 16373398 | Under similar conditions, insulin- or DHEA-stimulated phosphorylation of Akt (Ser473) and endothelial nitric oxide synthase (Ser1179) was inhibited by pretreatment of cells with wortmannin (but not MAPK kinase inhibitor PD98059). |
| 3663 | 16373398 | We conclude that DHEA has acute, nongenomic actions in endothelium to stimulate production of the vasodilator NO via PI 3-kinase-dependent pathways and secretion of the vasoconstrictor ET-1 via MAPK-dependent pathways. |
| 3664 | 16373417 | The transcription factor AP-2beta causes cell enlargement and insulin resistance in 3T3-L1 adipocytes. |
| 3665 | 16373417 | Thus, we overexpressed the AP-2beta gene in 3T3-L1 adipocytes to clarify whether AP-2beta might play a crucial role in the pathogenesis of type 2 diabetes through dysregulation of adipocyte function. |
| 3666 | 16373417 | Enhancement of glucose uptake by AP-2beta overexpression was attenuated by inhibitors of phospholipase C (PLC) and atypical protein kinase Czeta/lambda (PKCzeta/lambda), but not by a phosphatidylinositol 3-kinase (PI3-K) inhibitor. |
| 3667 | 16373417 | Consistently, we found activation of PLC and atypical PKC, but not PI3-K, by AP-2beta expression. |
| 3668 | 16373417 | Furthermore, overexpression of PLCgamma enhanced glucose uptake, and this activation was inhibited by an atypical PKC inhibitor, suggesting that the enhanced glucose uptake may be mediated through PLC and atypical PKCzeta/lambda, but not PI3-K. |
| 3669 | 16373417 | Finally, AP-2beta overexpression was found to relate to the impaired insulin signaling. |
| 3670 | 16373417 | We propose that AP-2beta is a candidate gene for producing adipocyte hypertrophy and may relate to the abnormal characteristics of adipocytes observed in obesity. |
| 3671 | 16373417 | The transcription factor AP-2beta causes cell enlargement and insulin resistance in 3T3-L1 adipocytes. |
| 3672 | 16373417 | Thus, we overexpressed the AP-2beta gene in 3T3-L1 adipocytes to clarify whether AP-2beta might play a crucial role in the pathogenesis of type 2 diabetes through dysregulation of adipocyte function. |
| 3673 | 16373417 | Enhancement of glucose uptake by AP-2beta overexpression was attenuated by inhibitors of phospholipase C (PLC) and atypical protein kinase Czeta/lambda (PKCzeta/lambda), but not by a phosphatidylinositol 3-kinase (PI3-K) inhibitor. |
| 3674 | 16373417 | Consistently, we found activation of PLC and atypical PKC, but not PI3-K, by AP-2beta expression. |
| 3675 | 16373417 | Furthermore, overexpression of PLCgamma enhanced glucose uptake, and this activation was inhibited by an atypical PKC inhibitor, suggesting that the enhanced glucose uptake may be mediated through PLC and atypical PKCzeta/lambda, but not PI3-K. |
| 3676 | 16373417 | Finally, AP-2beta overexpression was found to relate to the impaired insulin signaling. |
| 3677 | 16373417 | We propose that AP-2beta is a candidate gene for producing adipocyte hypertrophy and may relate to the abnormal characteristics of adipocytes observed in obesity. |
| 3678 | 16373417 | The transcription factor AP-2beta causes cell enlargement and insulin resistance in 3T3-L1 adipocytes. |
| 3679 | 16373417 | Thus, we overexpressed the AP-2beta gene in 3T3-L1 adipocytes to clarify whether AP-2beta might play a crucial role in the pathogenesis of type 2 diabetes through dysregulation of adipocyte function. |
| 3680 | 16373417 | Enhancement of glucose uptake by AP-2beta overexpression was attenuated by inhibitors of phospholipase C (PLC) and atypical protein kinase Czeta/lambda (PKCzeta/lambda), but not by a phosphatidylinositol 3-kinase (PI3-K) inhibitor. |
| 3681 | 16373417 | Consistently, we found activation of PLC and atypical PKC, but not PI3-K, by AP-2beta expression. |
| 3682 | 16373417 | Furthermore, overexpression of PLCgamma enhanced glucose uptake, and this activation was inhibited by an atypical PKC inhibitor, suggesting that the enhanced glucose uptake may be mediated through PLC and atypical PKCzeta/lambda, but not PI3-K. |
| 3683 | 16373417 | Finally, AP-2beta overexpression was found to relate to the impaired insulin signaling. |
| 3684 | 16373417 | We propose that AP-2beta is a candidate gene for producing adipocyte hypertrophy and may relate to the abnormal characteristics of adipocytes observed in obesity. |
| 3685 | 16375864 | In the present study, we found that Akt down-regulation is important for inducing CHOP expression, an ER stress-induced transcription factor. |
| 3686 | 16375864 | Interestingly, treatment with a PI3K inhibitor alone induced CHOP expression and caused cell death. |
| 3687 | 16375864 | However, a MEK1 inhibitor induced neither CHOP expression nor cell death. |
| 3688 | 16375864 | These results indicate that the inactivation of Akt by ER stress induces CHOP expression and causes cell death. |
| 3689 | 16399506 | Hypothalamic signaling via the insulin receptor substrate-phosphatidylinositol 3-kinase (IRS-PI3K) pathway, a key intracellular mediator of insulin action, was reduced in rats with uncontrolled diabetes induced by streptozotocin (STZ-DM). |
| 3690 | 16399506 | Further, infusion of a PI3K inhibitor into the third cerebral ventricle of STZ-DM rats prior to peripheral insulin injection attenuated insulin-induced glucose lowering by approximately 35%-40% in both acute and chronic insulin treatment paradigms. |
| 3691 | 16399506 | Conversely, increased PI3K signaling induced by hypothalamic overexpression of either IRS-2 or protein kinase B (PKB, a key downstream mediator of PI3K action) enhanced the glycemic response to insulin by approximately 2-fold in STZ-DM rats. |
| 3692 | 16399506 | Hypothalamic signaling via the insulin receptor substrate-phosphatidylinositol 3-kinase (IRS-PI3K) pathway, a key intracellular mediator of insulin action, was reduced in rats with uncontrolled diabetes induced by streptozotocin (STZ-DM). |
| 3693 | 16399506 | Further, infusion of a PI3K inhibitor into the third cerebral ventricle of STZ-DM rats prior to peripheral insulin injection attenuated insulin-induced glucose lowering by approximately 35%-40% in both acute and chronic insulin treatment paradigms. |
| 3694 | 16399506 | Conversely, increased PI3K signaling induced by hypothalamic overexpression of either IRS-2 or protein kinase B (PKB, a key downstream mediator of PI3K action) enhanced the glycemic response to insulin by approximately 2-fold in STZ-DM rats. |
| 3695 | 16399506 | Hypothalamic signaling via the insulin receptor substrate-phosphatidylinositol 3-kinase (IRS-PI3K) pathway, a key intracellular mediator of insulin action, was reduced in rats with uncontrolled diabetes induced by streptozotocin (STZ-DM). |
| 3696 | 16399506 | Further, infusion of a PI3K inhibitor into the third cerebral ventricle of STZ-DM rats prior to peripheral insulin injection attenuated insulin-induced glucose lowering by approximately 35%-40% in both acute and chronic insulin treatment paradigms. |
| 3697 | 16399506 | Conversely, increased PI3K signaling induced by hypothalamic overexpression of either IRS-2 or protein kinase B (PKB, a key downstream mediator of PI3K action) enhanced the glycemic response to insulin by approximately 2-fold in STZ-DM rats. |
| 3698 | 16411407 | Homocysteine effects were investigated also after cell exposure to i) specific MEK inhibitor PD98059 (30 micromol/l) to evaluate the involvement of Mitogen-Activated Protein Kinase (MAPK) and ii) specific phosphatidylinositol 3-kinase (P13-K) inhibitor LY294002 (100 micromol/l) to evaluate the involvement of P13-K pathway. |
| 3699 | 16411407 | Homocysteine, at concentrations associated with increased risk of cardiovascular events, increases MMP-2 activity, synthesis and secretion in VSMC through a mechanism involving the activation of MAPK and P13-K pathways. |
| 3700 | 16412093 | Alzheimer-like changes in protein kinase B and glycogen synthase kinase-3 in rat frontal cortex and hippocampus after damage to the insulin signalling pathway. |
| 3701 | 16412093 | The insulin-resistant brain state is related to late-onset sporadic Alzheimer's disease, and alterations in the insulin receptor (IR) and its downstream phosphatidylinositol-3 kinase signalling pathway have been found in human brain. |
| 3702 | 16412093 | In this study, western blot analysis performed 1 month after i.c.v. injection of STZ showed an increase of 63% in the level of phosphorylated glycogen synthase kinase-3alpha/beta (pGSK-3alpha/beta) protein in the rat hippocampus, whereas the levels of the unphosphorylated form (GSK-3alpha/beta) and protein kinase B (Akt/PKB) remained unchanged. |
| 3703 | 16424109 | Unlike insulin, the PI3-K inhibitor wortmannin did not reverse GE antilipolysis, and GE did not affect phosphorylation of protein kinase B (PKB). |
| 3704 | 16424109 | The specific phosphodiesterase 4 (PDE4) inhibitor rolipram did not significantly affect insulin antilipolysis, but almost completely reversed GE antilipolysis. |
| 3705 | 16443776 | SGK1 kinase upregulates GLUT1 activity and plasma membrane expression. |
| 3706 | 16443776 | Phosphatidylinositol 3-kinase (PI3 kinase) inhibition disrupts the ability of insulin to stimulate GLUT1 and GLUT4 translocation into the cell membrane and thus glucose transport. |
| 3707 | 16443776 | The effect on GLUT4 but not on GLUT1 is mediated by activation of protein kinase B (PKB). |
| 3708 | 16443776 | The serum- and glucocorticoid-inducible kinase SGK1, a further kinase downstream of PI3 kinase, regulates several transporters by enhancing their plasma membrane abundance. |
| 3709 | 16443776 | GLUT1 contains a consensus site ((95)Ser) for phosphorylation by SGK1. |
| 3710 | 16443776 | Tracer-flux studies in Xenopus oocytes and HEK-293 cells demonstrated that GLUT1 transport is enhanced by constitutively active (S422D)SGK1. |
| 3711 | 16443776 | The effect requires the kinase catalytical activity since the inactive mutant (K127N)SGK1 failed to modulate GLUT1. |
| 3712 | 16443776 | GLUT1 stimulation by (S422D)SGK1 is not due to de novo protein synthesis but rather to an increase of the transporter's abundance in the plasma membrane. |
| 3713 | 16443776 | Kinetic analysis revealed that SGK1 enhances maximal transport rate without altering GLUT1 substrate affinity. |
| 3714 | 16443776 | These observations suggest that SGK1 regulates GLUT1 and may contribute to or account for the PI3 kinase-dependent but PKB-independent stimulation of GLUT1 by insulin. |
| 3715 | 16446424 | Activation of the phosphatidylinositol 3-kinase (PI3K)-AKT/protein kinase B signaling pathway has been associated with multiple human cancers. |
| 3716 | 16446424 | Recently we showed that AKT is activated in both the thyroid and metastatic lesions of a mouse model of follicular thyroid carcinoma [thyroid hormone beta receptor (TRbeta)(PV/PV) mice]. |
| 3717 | 16446424 | Here we show that in thyroid tumors, PV mutant bound significantly more to the PI3K-regulatory subunit p85alpha, resulting in a greater increase in the kinase activity than did TRbeta1 in wild-type mice. |
| 3718 | 16446424 | By confocal fluorescence microscopy, p85alpha was shown to colocalize with TRbeta1 or PV mainly in the nuclear compartment of cultured tumor cells from TRbeta(PV/PV) mice, but cytoplasmic p85alpha/PV or p85alpha/TRbeta1 complexes were also detectable. |
| 3719 | 16446424 | Further biochemical analysis revealed that the activation of the PI3K-AKT-mammalian target of the rapamycin-p70(S6K) pathway was observed in both the cytoplasmic and nuclear compartments, whereas the activation of the PI3K-integrin-linked kinase-matrix metalloproteinase 2 pathway was detected mainly in the extranuclear compartments. |
| 3720 | 16446424 | These results suggest that PV, via the activation of p85alpha, could act to affect PI3K downstream signaling in both the nuclear and extranuclear compartments, thereby contributing to thyroid carcinogenesis. |
| 3721 | 16446424 | Activation of the phosphatidylinositol 3-kinase (PI3K)-AKT/protein kinase B signaling pathway has been associated with multiple human cancers. |
| 3722 | 16446424 | Recently we showed that AKT is activated in both the thyroid and metastatic lesions of a mouse model of follicular thyroid carcinoma [thyroid hormone beta receptor (TRbeta)(PV/PV) mice]. |
| 3723 | 16446424 | Here we show that in thyroid tumors, PV mutant bound significantly more to the PI3K-regulatory subunit p85alpha, resulting in a greater increase in the kinase activity than did TRbeta1 in wild-type mice. |
| 3724 | 16446424 | By confocal fluorescence microscopy, p85alpha was shown to colocalize with TRbeta1 or PV mainly in the nuclear compartment of cultured tumor cells from TRbeta(PV/PV) mice, but cytoplasmic p85alpha/PV or p85alpha/TRbeta1 complexes were also detectable. |
| 3725 | 16446424 | Further biochemical analysis revealed that the activation of the PI3K-AKT-mammalian target of the rapamycin-p70(S6K) pathway was observed in both the cytoplasmic and nuclear compartments, whereas the activation of the PI3K-integrin-linked kinase-matrix metalloproteinase 2 pathway was detected mainly in the extranuclear compartments. |
| 3726 | 16446424 | These results suggest that PV, via the activation of p85alpha, could act to affect PI3K downstream signaling in both the nuclear and extranuclear compartments, thereby contributing to thyroid carcinogenesis. |
| 3727 | 16446424 | Activation of the phosphatidylinositol 3-kinase (PI3K)-AKT/protein kinase B signaling pathway has been associated with multiple human cancers. |
| 3728 | 16446424 | Recently we showed that AKT is activated in both the thyroid and metastatic lesions of a mouse model of follicular thyroid carcinoma [thyroid hormone beta receptor (TRbeta)(PV/PV) mice]. |
| 3729 | 16446424 | Here we show that in thyroid tumors, PV mutant bound significantly more to the PI3K-regulatory subunit p85alpha, resulting in a greater increase in the kinase activity than did TRbeta1 in wild-type mice. |
| 3730 | 16446424 | By confocal fluorescence microscopy, p85alpha was shown to colocalize with TRbeta1 or PV mainly in the nuclear compartment of cultured tumor cells from TRbeta(PV/PV) mice, but cytoplasmic p85alpha/PV or p85alpha/TRbeta1 complexes were also detectable. |
| 3731 | 16446424 | Further biochemical analysis revealed that the activation of the PI3K-AKT-mammalian target of the rapamycin-p70(S6K) pathway was observed in both the cytoplasmic and nuclear compartments, whereas the activation of the PI3K-integrin-linked kinase-matrix metalloproteinase 2 pathway was detected mainly in the extranuclear compartments. |
| 3732 | 16446424 | These results suggest that PV, via the activation of p85alpha, could act to affect PI3K downstream signaling in both the nuclear and extranuclear compartments, thereby contributing to thyroid carcinogenesis. |
| 3733 | 16446424 | Activation of the phosphatidylinositol 3-kinase (PI3K)-AKT/protein kinase B signaling pathway has been associated with multiple human cancers. |
| 3734 | 16446424 | Recently we showed that AKT is activated in both the thyroid and metastatic lesions of a mouse model of follicular thyroid carcinoma [thyroid hormone beta receptor (TRbeta)(PV/PV) mice]. |
| 3735 | 16446424 | Here we show that in thyroid tumors, PV mutant bound significantly more to the PI3K-regulatory subunit p85alpha, resulting in a greater increase in the kinase activity than did TRbeta1 in wild-type mice. |
| 3736 | 16446424 | By confocal fluorescence microscopy, p85alpha was shown to colocalize with TRbeta1 or PV mainly in the nuclear compartment of cultured tumor cells from TRbeta(PV/PV) mice, but cytoplasmic p85alpha/PV or p85alpha/TRbeta1 complexes were also detectable. |
| 3737 | 16446424 | Further biochemical analysis revealed that the activation of the PI3K-AKT-mammalian target of the rapamycin-p70(S6K) pathway was observed in both the cytoplasmic and nuclear compartments, whereas the activation of the PI3K-integrin-linked kinase-matrix metalloproteinase 2 pathway was detected mainly in the extranuclear compartments. |
| 3738 | 16446424 | These results suggest that PV, via the activation of p85alpha, could act to affect PI3K downstream signaling in both the nuclear and extranuclear compartments, thereby contributing to thyroid carcinogenesis. |
| 3739 | 16452480 | Chronic ethanol intake impairs insulin signaling in rats by disrupting Akt association with the cell membrane. |
| 3740 | 16452480 | We previously reported elevations in hepatic Class 1 alcohol dehydrogenase (ADH) expression in ethanol-fed rats correspondent with reduced levels of mature, nuclear sterol-regulatory element-binding protein-1 (SREBP-1), an insulin-induced transcriptional repressor of the ADH gene. |
| 3741 | 16452480 | In this report, we have studied the effects of insulin and ethanol on ADH gene expression in a highly differentiated rat hepatoma cell line (FGC-4), as well as the in vivo effects of chronic intake of an ethanol-containing diet on hepatic insulin signaling. |
| 3742 | 16452480 | Insulin inhibited ADH gene expression, and this was abolished by LY294002 (a phosphatidylinositol 3-kinase inhibitor) and small interfering RNA knockdown of SREBP-1. |
| 3743 | 16452480 | Thus, disruptive effects of ethanol on insulin signaling occurred via impaired phosphorylation of Akt at Thr308. |
| 3744 | 16452480 | Ethanol inhibition of insulin signaling reduces nuclear SREBP accumulation and results in disinhibition of Class 1 ADH transcription. |
| 3745 | 16453015 | In this issue of the JCI, Anitha et al. report apoptosis of rodent enteric neurons under hyperglycemic conditions, both in vitro and in vivo, associated with impaired PI3K activity and preventable by glial cell line-derived neurotrophic factor. |
| 3746 | 16453021 | GDNF rescues hyperglycemia-induced diabetic enteric neuropathy through activation of the PI3K/Akt pathway. |
| 3747 | 16453021 | Exposure to 20 mM glucose resulted in decreased Akt phosphorylation and enhanced nuclear translocation of forkhead box O3a (FOXO3a). |
| 3748 | 16453021 | The pathophysiological effects of hyperglycemia (apoptosis, reduced Akt phosphorylation, loss of inhibitory neurons, motility changes) were reversed in diabetic glial fibrillary acidic protein-GDNF (GFAP-GDNF) Tg mice. |
| 3749 | 16455778 | Insulin effects on both islet cell K(ATP) channels were blocked by wortmannin, indicating that insulin acted on the insulin receptor-phosphatidylinositol 3-kinase signaling pathway. |
| 3750 | 16456236 | The molecular mechanism responsible for the insulin-like effects of vanadium compounds have been shown to involve the activation of several key components of insulin-signaling pathways that include the mitogen-activated-protein kinases (MAPKs) extracellular signal-regulated kinase 1/2 (ERK1/2) and p38MAPK, and phosphatidylinositol 3-kinase (PI3-K)/protein kinase B (PKB). |
| 3751 | 16456236 | Because MAPK and PI3-K/PKB pathways are implicated in mediating the mitogenic and metabolic effects of insulin, respectively, it is plausible that mimicry of these pathways by vanadium serves as a mechanism for its insulin-like responses. |
| 3752 | 16456236 | The molecular mechanism responsible for the insulin-like effects of vanadium compounds have been shown to involve the activation of several key components of insulin-signaling pathways that include the mitogen-activated-protein kinases (MAPKs) extracellular signal-regulated kinase 1/2 (ERK1/2) and p38MAPK, and phosphatidylinositol 3-kinase (PI3-K)/protein kinase B (PKB). |
| 3753 | 16456236 | Because MAPK and PI3-K/PKB pathways are implicated in mediating the mitogenic and metabolic effects of insulin, respectively, it is plausible that mimicry of these pathways by vanadium serves as a mechanism for its insulin-like responses. |
| 3754 | 16460957 | Cross-talk between G-protein-coupled receptors and tyrosine kinases can occur at several levels, including the receptor-to-receptor level, and at crucial downstream points (e.g. phosphatidylinositol-3-kinase, Akt/protein kinase B and the mitogen-activated protein kinase cascade). |
| 3755 | 16469952 | Regulation of vascular endothelial growth factor expression and vascularization in the myocardium by insulin receptor and PI3K/Akt pathways in insulin resistance and ischemia. |
| 3756 | 16492903 | In metabolic tissues, insulin signaling via the phosphatidylinositol-3-kinase pathway leads to glucose uptake so that in insulin resistance a state of hyperglycemia occurs; other factors such as dyslipidemia and hypertension also arise. |
| 3757 | 16492903 | In cardiovascular tissues there are two pathways of insulin receptor signaling, one that is predominant in metabolic tissues (mediated by phosphatidylinositol-3-kinase) and another being a growth factor-like pathway (mediated by MAPK); the down-regulation of the former and continued activity of the latter pathway leads to atherosclerosis. |
| 3758 | 16492903 | In metabolic tissues, insulin signaling via the phosphatidylinositol-3-kinase pathway leads to glucose uptake so that in insulin resistance a state of hyperglycemia occurs; other factors such as dyslipidemia and hypertension also arise. |
| 3759 | 16492903 | In cardiovascular tissues there are two pathways of insulin receptor signaling, one that is predominant in metabolic tissues (mediated by phosphatidylinositol-3-kinase) and another being a growth factor-like pathway (mediated by MAPK); the down-regulation of the former and continued activity of the latter pathway leads to atherosclerosis. |
| 3760 | 16505233 | Overexpression of suppressor of cytokine signaling 3 in adipose tissue causes local but not systemic insulin resistance. |
| 3761 | 16505233 | In adipocytes, suppressor of cytokine signaling (SOCS)3 deficiency increases insulin-stimulated insulin receptor substrate (IRS)-1 and -2 phosphorylation, IRS-associated phosphatidylinositol 3 kinase activity, and insulin-stimulated glucose uptake. |
| 3762 | 16505233 | Moreover, SOCS3 is required for tumor necrosis factor-alpha full inhibition of insulin-stimulated IRS-1 and -2 phosphorylation, phosphatidylinositol 3 kinase activity, and glucose uptake. |
| 3763 | 16505233 | Whether SOCS3 also inhibits adipocyte insulin signaling in vivo and whether this action further affects systemic insulin sensitivity is not clear. |
| 3764 | 16505233 | Overexpression of SOCS3 in adipocytes decreases IRS1 protein levels and subsequent insulin-stimulated IRS-1 and -2 phosphorylation, decreases p85 binding to IRS-1, and leads to decreased insulin-stimulated glucose uptake in adipocytes. |
| 3765 | 16505233 | This impaired insulin signaling in adipose tissue of aP2-SOCS3 mice causes decreased lipogenesis and blocks insulin's antilipolytic action. |
| 3766 | 16505233 | However, because of decreased energy partitioning in adipose tissue, aP2-SOCS3 mice are resistant to diet-induced obesity and are protected against systemic insulin resistance caused by a high-fat diet. |
| 3767 | 16505233 | Therefore, overexpression of SOCS3 in adipocytes causes local adipocyte insulin resistance, but it is not sufficient to cause systemic insulin resistance. |
| 3768 | 16505233 | Overexpression of suppressor of cytokine signaling 3 in adipose tissue causes local but not systemic insulin resistance. |
| 3769 | 16505233 | In adipocytes, suppressor of cytokine signaling (SOCS)3 deficiency increases insulin-stimulated insulin receptor substrate (IRS)-1 and -2 phosphorylation, IRS-associated phosphatidylinositol 3 kinase activity, and insulin-stimulated glucose uptake. |
| 3770 | 16505233 | Moreover, SOCS3 is required for tumor necrosis factor-alpha full inhibition of insulin-stimulated IRS-1 and -2 phosphorylation, phosphatidylinositol 3 kinase activity, and glucose uptake. |
| 3771 | 16505233 | Whether SOCS3 also inhibits adipocyte insulin signaling in vivo and whether this action further affects systemic insulin sensitivity is not clear. |
| 3772 | 16505233 | Overexpression of SOCS3 in adipocytes decreases IRS1 protein levels and subsequent insulin-stimulated IRS-1 and -2 phosphorylation, decreases p85 binding to IRS-1, and leads to decreased insulin-stimulated glucose uptake in adipocytes. |
| 3773 | 16505233 | This impaired insulin signaling in adipose tissue of aP2-SOCS3 mice causes decreased lipogenesis and blocks insulin's antilipolytic action. |
| 3774 | 16505233 | However, because of decreased energy partitioning in adipose tissue, aP2-SOCS3 mice are resistant to diet-induced obesity and are protected against systemic insulin resistance caused by a high-fat diet. |
| 3775 | 16505233 | Therefore, overexpression of SOCS3 in adipocytes causes local adipocyte insulin resistance, but it is not sufficient to cause systemic insulin resistance. |
| 3776 | 16505239 | Extracellular signal-regulated kinase (ERK)1/2 activation was increased in skeletal muscle tissue and in cultured myotubes basally and in response to insulin in women with PCOS compared with control women. |
| 3777 | 16505239 | Mitogen-activated/extracellular signal-regulated kinase kinase (MEK)1/2 was also activated in PCOS, whereas p38 mitogen-activated protein kinase phosphorylation and signaling from the insulin receptor to Grb2 was similar in both groups. |
| 3778 | 16505239 | MEK1/2 inhibition reduced IRS-1 Ser312 phosphorylation and increased IRS-1 association with the p85 subunit of phosphatidylinositol 3-kinase in both groups. |
| 3779 | 16505239 | We conclude that in PCOS skeletal muscle, 1) mitogenic signaling is enhanced in vivo and in culture, 2) ERK1/2 activation inhibits association of IRS-1 with p85 via IRS-1 Ser312 phosphorylation, and 3) ERK1/2 activation may play a role in normal feedback of insulin signaling and contribute to resistance to insulin's metabolic actions in PCOS. |
| 3780 | 16505244 | IRS-1 serine phosphorylation and insulin resistance in skeletal muscle from pancreas transplant recipients. |
| 3781 | 16505244 | Basal insulin receptor substrate (IRS)-1 Ser (312) and Ser (616) phosphorylation, IRS-1-associated phosphatidylinositol 3-kinase activity, and extracellular signal-regulated kinase (ERK)-1/2 phosphorylation were elevated in pancreas-kidney transplant recipients, coincident with fasting hyperinsulinemia. |
| 3782 | 16505244 | Insulin increased phosphorylation of IRS-1 at Ser (312) but not Ser (616) in healthy subjects, with impairments noted in nondiabetic kidney and pancreas-kidney transplant recipients. |
| 3783 | 16505244 | Insulin action on ERK-1/2 and Akt phosphorylation was impaired in pancreas-kidney transplant recipients and was preserved in nondiabetic kidney transplant recipients. |
| 3784 | 16505244 | Importantly, insulin stimulation of the Akt substrate AS160 was impaired in nondiabetic kidney and pancreas-kidney transplant recipients. |
| 3785 | 16505244 | In conclusion, peripheral insulin resistance in pancreas-kidney transplant recipients may arise from a negative feedback regulation of the canonical insulin-signaling cascade from excessive serine phosphorylation of IRS-1, possibly as a consequence of immunosuppressive therapy and hyperinsulinemia. |
| 3786 | 16506055 | Insulin activates hypoxia-inducible factor-1alpha in human and rat vascular smooth muscle cells via phosphatidylinositol-3 kinase and mitogen-activated protein kinase pathways: impairment in insulin resistance owing to defects in insulin signalling. |
| 3787 | 16510765 | The aim was to investigate whether C-peptide or insulin could modulate TNF-alpha-mediated cell death in opossum kidney proximal tubular cells and to examine the mechanism(s) of any effects observed. |
| 3788 | 16510765 | C-peptide and insulin protect against TNF-alpha-induced proximal tubular cell toxicity and apoptosis. |
| 3789 | 16510765 | By ELISA assay, 300 ng/ml TNF-alpha increased apoptosis by 145.8 +/- 4.9% compared with controls, whereas 5 nM C-peptide and 100 nM insulin reduced apoptosis to 81.6 +/- 4.8 and 77.4 +/- 3.1% of control, respectively. |
| 3790 | 16510765 | The protective effects of C-peptide and insulin were associated with activation of NF-kappaB. |
| 3791 | 16510765 | Phosphatidylinositol 3-kinase but not extracellular signal regulated mitogen-activated protein kinase mediated C-peptide and insulin activation of NF-kappaB. |
| 3792 | 16510765 | The cytoprotective effects of both C-peptide and insulin were related to increased expression of TNF receptor-associated factor 2, the product of an NF-kappaB-dependent survival gene. |
| 3793 | 16510765 | These data suggest that C-peptide and/or insulin activation of NF-kappaB-regulated survival genes protects against TNF-alpha-induced renal tubular injury in diabetes. |
| 3794 | 16517941 | ANG II enhances contractile responses via PI3-kinase p110 delta pathway in aortas from diabetic rats with systemic hyperinsulinemia. |
| 3795 | 16517941 | We investigated the involvement of ANG II and phosphatidylinositol 3-kinase (PI3-K) in the enhanced aortic contractile responses induced by hyperinsulinemia in chronic insulin-treated Type 1 diabetic rats. |
| 3796 | 16517941 | Plasma ANG II levels were elevated in untreated compared with control diabetic rats and further increased in insulin-treated diabetic rats. |
| 3797 | 16517941 | These insulin-induced increases were largely prevented by cotreatment with losartan (an ANG II type 1 receptor antagonist) or enalapril (an angiotensin-converting enzyme inhibitor). |
| 3798 | 16517941 | LY-294002 (a PI3-K inhibitor) diminished the increases in contractile responses in ANG II-incubated aortas and aortas from chronic insulin-treated diabetic rats. |
| 3799 | 16517941 | The norepinephrine (NE)-stimulated levels of p110 delta-associated PI3-K activity and p110 delta protein expression were increased in aortas from insulin-treated diabetic compared with control and untreated diabetic rats, and chronic administration of losartan blunted these increases. |
| 3800 | 16517941 | NE-stimulated p110 PI3-K activity was elevated in aortas from diabetic rats coincubated with a noncontractile dose of ANG II. |
| 3801 | 16517941 | These results suggest that, in insulin-treated Type 1 diabetic rats with hyperinsulinemia, chronic ANG II type 1 receptor blockade blunts the increases in vascular contractility and blood pressure via a decrease in p110 delta-associated PI3-K activity. |
| 3802 | 16517941 | ANG II enhances contractile responses via PI3-kinase p110 delta pathway in aortas from diabetic rats with systemic hyperinsulinemia. |
| 3803 | 16517941 | We investigated the involvement of ANG II and phosphatidylinositol 3-kinase (PI3-K) in the enhanced aortic contractile responses induced by hyperinsulinemia in chronic insulin-treated Type 1 diabetic rats. |
| 3804 | 16517941 | Plasma ANG II levels were elevated in untreated compared with control diabetic rats and further increased in insulin-treated diabetic rats. |
| 3805 | 16517941 | These insulin-induced increases were largely prevented by cotreatment with losartan (an ANG II type 1 receptor antagonist) or enalapril (an angiotensin-converting enzyme inhibitor). |
| 3806 | 16517941 | LY-294002 (a PI3-K inhibitor) diminished the increases in contractile responses in ANG II-incubated aortas and aortas from chronic insulin-treated diabetic rats. |
| 3807 | 16517941 | The norepinephrine (NE)-stimulated levels of p110 delta-associated PI3-K activity and p110 delta protein expression were increased in aortas from insulin-treated diabetic compared with control and untreated diabetic rats, and chronic administration of losartan blunted these increases. |
| 3808 | 16517941 | NE-stimulated p110 PI3-K activity was elevated in aortas from diabetic rats coincubated with a noncontractile dose of ANG II. |
| 3809 | 16517941 | These results suggest that, in insulin-treated Type 1 diabetic rats with hyperinsulinemia, chronic ANG II type 1 receptor blockade blunts the increases in vascular contractility and blood pressure via a decrease in p110 delta-associated PI3-K activity. |
| 3810 | 16517941 | ANG II enhances contractile responses via PI3-kinase p110 delta pathway in aortas from diabetic rats with systemic hyperinsulinemia. |
| 3811 | 16517941 | We investigated the involvement of ANG II and phosphatidylinositol 3-kinase (PI3-K) in the enhanced aortic contractile responses induced by hyperinsulinemia in chronic insulin-treated Type 1 diabetic rats. |
| 3812 | 16517941 | Plasma ANG II levels were elevated in untreated compared with control diabetic rats and further increased in insulin-treated diabetic rats. |
| 3813 | 16517941 | These insulin-induced increases were largely prevented by cotreatment with losartan (an ANG II type 1 receptor antagonist) or enalapril (an angiotensin-converting enzyme inhibitor). |
| 3814 | 16517941 | LY-294002 (a PI3-K inhibitor) diminished the increases in contractile responses in ANG II-incubated aortas and aortas from chronic insulin-treated diabetic rats. |
| 3815 | 16517941 | The norepinephrine (NE)-stimulated levels of p110 delta-associated PI3-K activity and p110 delta protein expression were increased in aortas from insulin-treated diabetic compared with control and untreated diabetic rats, and chronic administration of losartan blunted these increases. |
| 3816 | 16517941 | NE-stimulated p110 PI3-K activity was elevated in aortas from diabetic rats coincubated with a noncontractile dose of ANG II. |
| 3817 | 16517941 | These results suggest that, in insulin-treated Type 1 diabetic rats with hyperinsulinemia, chronic ANG II type 1 receptor blockade blunts the increases in vascular contractility and blood pressure via a decrease in p110 delta-associated PI3-K activity. |
| 3818 | 16517941 | ANG II enhances contractile responses via PI3-kinase p110 delta pathway in aortas from diabetic rats with systemic hyperinsulinemia. |
| 3819 | 16517941 | We investigated the involvement of ANG II and phosphatidylinositol 3-kinase (PI3-K) in the enhanced aortic contractile responses induced by hyperinsulinemia in chronic insulin-treated Type 1 diabetic rats. |
| 3820 | 16517941 | Plasma ANG II levels were elevated in untreated compared with control diabetic rats and further increased in insulin-treated diabetic rats. |
| 3821 | 16517941 | These insulin-induced increases were largely prevented by cotreatment with losartan (an ANG II type 1 receptor antagonist) or enalapril (an angiotensin-converting enzyme inhibitor). |
| 3822 | 16517941 | LY-294002 (a PI3-K inhibitor) diminished the increases in contractile responses in ANG II-incubated aortas and aortas from chronic insulin-treated diabetic rats. |
| 3823 | 16517941 | The norepinephrine (NE)-stimulated levels of p110 delta-associated PI3-K activity and p110 delta protein expression were increased in aortas from insulin-treated diabetic compared with control and untreated diabetic rats, and chronic administration of losartan blunted these increases. |
| 3824 | 16517941 | NE-stimulated p110 PI3-K activity was elevated in aortas from diabetic rats coincubated with a noncontractile dose of ANG II. |
| 3825 | 16517941 | These results suggest that, in insulin-treated Type 1 diabetic rats with hyperinsulinemia, chronic ANG II type 1 receptor blockade blunts the increases in vascular contractility and blood pressure via a decrease in p110 delta-associated PI3-K activity. |
| 3826 | 16517941 | ANG II enhances contractile responses via PI3-kinase p110 delta pathway in aortas from diabetic rats with systemic hyperinsulinemia. |
| 3827 | 16517941 | We investigated the involvement of ANG II and phosphatidylinositol 3-kinase (PI3-K) in the enhanced aortic contractile responses induced by hyperinsulinemia in chronic insulin-treated Type 1 diabetic rats. |
| 3828 | 16517941 | Plasma ANG II levels were elevated in untreated compared with control diabetic rats and further increased in insulin-treated diabetic rats. |
| 3829 | 16517941 | These insulin-induced increases were largely prevented by cotreatment with losartan (an ANG II type 1 receptor antagonist) or enalapril (an angiotensin-converting enzyme inhibitor). |
| 3830 | 16517941 | LY-294002 (a PI3-K inhibitor) diminished the increases in contractile responses in ANG II-incubated aortas and aortas from chronic insulin-treated diabetic rats. |
| 3831 | 16517941 | The norepinephrine (NE)-stimulated levels of p110 delta-associated PI3-K activity and p110 delta protein expression were increased in aortas from insulin-treated diabetic compared with control and untreated diabetic rats, and chronic administration of losartan blunted these increases. |
| 3832 | 16517941 | NE-stimulated p110 PI3-K activity was elevated in aortas from diabetic rats coincubated with a noncontractile dose of ANG II. |
| 3833 | 16517941 | These results suggest that, in insulin-treated Type 1 diabetic rats with hyperinsulinemia, chronic ANG II type 1 receptor blockade blunts the increases in vascular contractility and blood pressure via a decrease in p110 delta-associated PI3-K activity. |
| 3834 | 16522728 | The incretin hormones, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP), have been suggested to act as beta-cell growth factors and may therefore be of critical importance for the maintenance of a proper beta-cell mass. |
| 3835 | 16522728 | GLP-1, GIP and the long-acting GLP-1 derivative, liraglutide, increased beta-cell replication 50-80% at 10-100 nM upon a 24 h stimulus, whereas glucagon at a similar concentration had no significant effect. |
| 3836 | 16522728 | The stimulatory effect of GLP-1 and GIP was efficiently mimicked by the adenylate cyclase activator, forskolin, at 10 nM (approximately 90% increase) and was additive (approximately 170-250% increase) with the growth response to human growth hormone (hGH), indicating the use of distinct intracellular signalling pathways leading to mitosis by incretins and cytokines, respectively. |
| 3837 | 16522728 | The response to both GLP-1 and GIP was completely blocked by the protein kinase A (PKA) inhibitor, H89. |
| 3838 | 16522728 | In addition, the phosphoinositol 3-kinase (PI3K) inhibitor wortmannin and the mitogen-activated protein kinase kinase (MEK) inhibitor PD98059, both inhibited GLP-1- and GIP-stimulated proliferation. |
| 3839 | 16522728 | The p38 mitogen-activated protein kinase (MAPK) inhibitor, SB203580, had no inhibitory effect on either GLP-1 or GIP stimulated proliferation. |
| 3840 | 16522728 | GLP-1 time-dependently induced the cyclin D1 mRNA and protein levels in INS-1E, whereas the cyclin D2 levels were unaffected. |
| 3841 | 16522728 | However, minor effect of GLP-1 stimulation was observed on the cyclin D3 mRNA levels. |
| 3842 | 16522728 | Transient transfection of a cyclin D1 promoter-luciferase reporter construct into islet monolayer cells or INS-1 cells revealed approximately a 2-3 fold increase of transcriptional activity in response to GLP-1 and GIP, and a 4-7 fold increase in response to forskolin. |
| 3843 | 16522728 | The stimulation of the cyclin D1 promoter by GLP-1 was inhibited by H89, wortmannin, and PD98059. |
| 3844 | 16522728 | We conclude that incretin-induced beta-cell replication is dependent on cAMP/PKA, p42 MAPK and PI3K activities, which may involve transcriptional induction of cyclin D1. |
| 3845 | 16522728 | GLP-1, GIP and liraglutide may have the potential to increase beta-cell replication in humans which would have significant impact on long-term diabetes treatment. |
| 3846 | 16522728 | The incretin hormones, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP), have been suggested to act as beta-cell growth factors and may therefore be of critical importance for the maintenance of a proper beta-cell mass. |
| 3847 | 16522728 | GLP-1, GIP and the long-acting GLP-1 derivative, liraglutide, increased beta-cell replication 50-80% at 10-100 nM upon a 24 h stimulus, whereas glucagon at a similar concentration had no significant effect. |
| 3848 | 16522728 | The stimulatory effect of GLP-1 and GIP was efficiently mimicked by the adenylate cyclase activator, forskolin, at 10 nM (approximately 90% increase) and was additive (approximately 170-250% increase) with the growth response to human growth hormone (hGH), indicating the use of distinct intracellular signalling pathways leading to mitosis by incretins and cytokines, respectively. |
| 3849 | 16522728 | The response to both GLP-1 and GIP was completely blocked by the protein kinase A (PKA) inhibitor, H89. |
| 3850 | 16522728 | In addition, the phosphoinositol 3-kinase (PI3K) inhibitor wortmannin and the mitogen-activated protein kinase kinase (MEK) inhibitor PD98059, both inhibited GLP-1- and GIP-stimulated proliferation. |
| 3851 | 16522728 | The p38 mitogen-activated protein kinase (MAPK) inhibitor, SB203580, had no inhibitory effect on either GLP-1 or GIP stimulated proliferation. |
| 3852 | 16522728 | GLP-1 time-dependently induced the cyclin D1 mRNA and protein levels in INS-1E, whereas the cyclin D2 levels were unaffected. |
| 3853 | 16522728 | However, minor effect of GLP-1 stimulation was observed on the cyclin D3 mRNA levels. |
| 3854 | 16522728 | Transient transfection of a cyclin D1 promoter-luciferase reporter construct into islet monolayer cells or INS-1 cells revealed approximately a 2-3 fold increase of transcriptional activity in response to GLP-1 and GIP, and a 4-7 fold increase in response to forskolin. |
| 3855 | 16522728 | The stimulation of the cyclin D1 promoter by GLP-1 was inhibited by H89, wortmannin, and PD98059. |
| 3856 | 16522728 | We conclude that incretin-induced beta-cell replication is dependent on cAMP/PKA, p42 MAPK and PI3K activities, which may involve transcriptional induction of cyclin D1. |
| 3857 | 16522728 | GLP-1, GIP and liraglutide may have the potential to increase beta-cell replication in humans which would have significant impact on long-term diabetes treatment. |
| 3858 | 16537919 | Phosphatase and tensin homologue deleted on chromosome 10 (PTEN) is a lipid phosphatase. |
| 3859 | 16537919 | PTEN inhibits the action of phosphatidylinositol-3-kinase and reduces the levels of phosphatidylinositol triphosphate, a crucial second messenger for cell proliferation and survival, as well as insulin signaling. |
| 3860 | 16537919 | In this study, we deleted Pten specifically in the insulin producing beta cells during murine pancreatic development. |
| 3861 | 16557003 | The PI3-K/Akt pathway: roles related to alterations in vasomotor responses in diabetic models. |
| 3862 | 16557003 | The principal mediators of diabetes-associated endothelial dysfunction are (a) increases in oxidized low density lipoprotein, endothelin-1, angiotensin II, oxidative stress, and (b) decreases in the actions of insulin or growth factors in endothelial cells. |
| 3863 | 16557003 | An accumulating body of evidence indicates that abnormal regulation of the phosphatidylinositol 3-kinase (PI3-K)/Akt pathway may be one of several factors contributing to vascular dysfunction in diabetes. |
| 3864 | 16557003 | The PI3-K pathway, which activates serine/threonine protein kinase Akt, enhances NO synthase phosphorylation and NO production. |
| 3865 | 16557003 | Several studies suggest that in diabetes the relative ineffectiveness of insulin and the hyperglycemia act together to reduce activity in the insulin-receptor substrates (IRS)/PI3-K/Akt pathway, resulting in impairments of both IRS/PI3-K/Akt-mediated endothelial function and NO production. |
| 3866 | 16557003 | This article summarizes the PI3-K/Akt pathway-mediated contraction and relaxation responses induced by various agents in the blood vessels of diabetic animals. |
| 3867 | 16557003 | The PI3-K/Akt pathway: roles related to alterations in vasomotor responses in diabetic models. |
| 3868 | 16557003 | The principal mediators of diabetes-associated endothelial dysfunction are (a) increases in oxidized low density lipoprotein, endothelin-1, angiotensin II, oxidative stress, and (b) decreases in the actions of insulin or growth factors in endothelial cells. |
| 3869 | 16557003 | An accumulating body of evidence indicates that abnormal regulation of the phosphatidylinositol 3-kinase (PI3-K)/Akt pathway may be one of several factors contributing to vascular dysfunction in diabetes. |
| 3870 | 16557003 | The PI3-K pathway, which activates serine/threonine protein kinase Akt, enhances NO synthase phosphorylation and NO production. |
| 3871 | 16557003 | Several studies suggest that in diabetes the relative ineffectiveness of insulin and the hyperglycemia act together to reduce activity in the insulin-receptor substrates (IRS)/PI3-K/Akt pathway, resulting in impairments of both IRS/PI3-K/Akt-mediated endothelial function and NO production. |
| 3872 | 16557003 | This article summarizes the PI3-K/Akt pathway-mediated contraction and relaxation responses induced by various agents in the blood vessels of diabetic animals. |
| 3873 | 16557003 | The PI3-K/Akt pathway: roles related to alterations in vasomotor responses in diabetic models. |
| 3874 | 16557003 | The principal mediators of diabetes-associated endothelial dysfunction are (a) increases in oxidized low density lipoprotein, endothelin-1, angiotensin II, oxidative stress, and (b) decreases in the actions of insulin or growth factors in endothelial cells. |
| 3875 | 16557003 | An accumulating body of evidence indicates that abnormal regulation of the phosphatidylinositol 3-kinase (PI3-K)/Akt pathway may be one of several factors contributing to vascular dysfunction in diabetes. |
| 3876 | 16557003 | The PI3-K pathway, which activates serine/threonine protein kinase Akt, enhances NO synthase phosphorylation and NO production. |
| 3877 | 16557003 | Several studies suggest that in diabetes the relative ineffectiveness of insulin and the hyperglycemia act together to reduce activity in the insulin-receptor substrates (IRS)/PI3-K/Akt pathway, resulting in impairments of both IRS/PI3-K/Akt-mediated endothelial function and NO production. |
| 3878 | 16557003 | This article summarizes the PI3-K/Akt pathway-mediated contraction and relaxation responses induced by various agents in the blood vessels of diabetic animals. |
| 3879 | 16557003 | The PI3-K/Akt pathway: roles related to alterations in vasomotor responses in diabetic models. |
| 3880 | 16557003 | The principal mediators of diabetes-associated endothelial dysfunction are (a) increases in oxidized low density lipoprotein, endothelin-1, angiotensin II, oxidative stress, and (b) decreases in the actions of insulin or growth factors in endothelial cells. |
| 3881 | 16557003 | An accumulating body of evidence indicates that abnormal regulation of the phosphatidylinositol 3-kinase (PI3-K)/Akt pathway may be one of several factors contributing to vascular dysfunction in diabetes. |
| 3882 | 16557003 | The PI3-K pathway, which activates serine/threonine protein kinase Akt, enhances NO synthase phosphorylation and NO production. |
| 3883 | 16557003 | Several studies suggest that in diabetes the relative ineffectiveness of insulin and the hyperglycemia act together to reduce activity in the insulin-receptor substrates (IRS)/PI3-K/Akt pathway, resulting in impairments of both IRS/PI3-K/Akt-mediated endothelial function and NO production. |
| 3884 | 16557003 | This article summarizes the PI3-K/Akt pathway-mediated contraction and relaxation responses induced by various agents in the blood vessels of diabetic animals. |
| 3885 | 16557003 | The PI3-K/Akt pathway: roles related to alterations in vasomotor responses in diabetic models. |
| 3886 | 16557003 | The principal mediators of diabetes-associated endothelial dysfunction are (a) increases in oxidized low density lipoprotein, endothelin-1, angiotensin II, oxidative stress, and (b) decreases in the actions of insulin or growth factors in endothelial cells. |
| 3887 | 16557003 | An accumulating body of evidence indicates that abnormal regulation of the phosphatidylinositol 3-kinase (PI3-K)/Akt pathway may be one of several factors contributing to vascular dysfunction in diabetes. |
| 3888 | 16557003 | The PI3-K pathway, which activates serine/threonine protein kinase Akt, enhances NO synthase phosphorylation and NO production. |
| 3889 | 16557003 | Several studies suggest that in diabetes the relative ineffectiveness of insulin and the hyperglycemia act together to reduce activity in the insulin-receptor substrates (IRS)/PI3-K/Akt pathway, resulting in impairments of both IRS/PI3-K/Akt-mediated endothelial function and NO production. |
| 3890 | 16557003 | This article summarizes the PI3-K/Akt pathway-mediated contraction and relaxation responses induced by various agents in the blood vessels of diabetic animals. |
| 3891 | 16567505 | 5-Aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside and metformin inhibit hepatic glucose phosphorylation by an AMP-activated protein kinase-independent effect on glucokinase translocation. |
| 3892 | 16567505 | We report here that 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside (AICAR), metformin, and oligomycin activated AMPK and inhibited glucose phosphorylation and glycolysis in rat hepatocytes. |
| 3893 | 16567505 | In vitro experiments demonstrated that this inhibition was not due to direct phosphorylation of glucokinase or its regulatory protein by AMPK. |
| 3894 | 16567505 | By contrast, AMPK phosphorylated liver 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase without affecting activity. |
| 3895 | 16567505 | Inhibitors of the endothelial nitric oxide synthase, stress kinases, and phosphatidylinositol 3-kinase pathways did not counteract the effects of AICAR, metformin, or oligomycin, suggesting that these signaling pathways were not involved. |
| 3896 | 16567505 | Finally, AICAR, metformin, and oligomycin were found to inhibit the glucose-induced translocation of glucokinase from the nucleus to the cytosol by a mechanism that could be related to the decrease in intracellular ATP concentrations observed in these conditions. |
| 3897 | 16567541 | We previously showed that insulin mediates a prosurvival pathway in retinal neurons and that normal retina expresses a highly active basal insulin receptor/Akt signaling pathway that is stable throughout feeding and fasting. |
| 3898 | 16567541 | The expression, phosphorylation status, and/or kinase activity of the insulin receptor and downstream signaling proteins were investigated in retinas of age-matched control, diabetic, and insulin-treated diabetic rats. |
| 3899 | 16567541 | Four weeks of diabetes reduced basal insulin receptor kinase, insulin receptor substrate (IRS)-1/2-associated phosphatidylinositol 3-kinase, and Akt kinase activity without altering insulin receptor or IRS-1/2 expression or tyrosine phosphorylation. |
| 3900 | 16567541 | After 12 weeks of diabetes, constitutive insulin receptor autophosphorylation and IRS-2 expression were reduced, without changes in p42/p44 mitogen-activated protein kinase or IRS-1. |
| 3901 | 16567541 | Sustained systemic insulin treatment of diabetic rats prevented loss of insulin receptor and Akt kinase activity, and acute intravitreal insulin administration restored insulin receptor kinase activity. |
| 3902 | 16567541 | Insulin treatment restored insulin receptor-beta autophosphorylation in rat retinas maintained ex vivo, demonstrating functional receptors and suggesting loss of ligand as a cause for reduced retinal insulin receptor/Akt pathway activity. |
| 3903 | 16567541 | These results demonstrate that diabetes progressively impairs the constitutive retinal insulin receptor signaling pathway through Akt and suggests that loss of this survival pathway may contribute to the initial stages of diabetic retinopathy. |
| 3904 | 16569213 | Angiotensin II stimulates phosphorylation of an ectodomain-truncated platelet-derived growth factor receptor-beta and its binding to class IA PI3K in vascular smooth muscle cells. |
| 3905 | 16569213 | PI3K (phosphoinositide 3-kinase) activity is involved in Ang (angiotensin) II-stimulated VSMC (vascular smooth muscle cell) growth and hypertrophy. |
| 3906 | 16569213 | In the present study, we demonstrate that the inhibition of PI3K in VSMCs by expression of a dominant-negative p85alpha mutant lacking the p110-binding domain (Deltap85), or by treatment of cells with LY294002, inhibited Ang II-stimulated PAI-1 (plasminogen activator inhibitor-1) mRNA expression. |
| 3907 | 16569213 | Using a GST (glutathione S-transferase) fusion protein containing the p85 N-terminal SH2 (Src homology 2) domain as 'bait' followed by MS/MS (tandem MS), we identified a 70 kDa fragment of the p70 PDGFR-beta (platelet-derived growth factor receptor-beta) as a signalling adapter that is phosphorylated and recruits the p85 subunit of PI3K after Ang II stimulation of AT1 (Ang II subtype 1) receptors on VSMCs. |
| 3908 | 16569213 | Stimulation of VSMCs with Ang II increased tyrosine-phosphorylation of p70 PDGFR-beta at Tyr751 and Tyr1021 and increased its binding to p85. |
| 3909 | 16569213 | PDGF also induced phosphorylation of p70 PDGFR-beta, a response inhibited by the PDGF tyrosine kinase selective inhibitor, AG1296. |
| 3910 | 16569213 | Ang II-stimulated phosphorylation of the p70 PDGFR-beta was blocked by the AT1 receptor antagonist, candesartan (CV 11974) and was partially inhibited by PP2 {4-amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine}, an Src family kinase inhibitor. |
| 3911 | 16569213 | Our result suggests that the p70 PDGFR-beta functions as an adapter that recruits PI3K to the membrane upon AT1 receptor stimulation. |
| 3912 | 16569213 | Angiotensin II stimulates phosphorylation of an ectodomain-truncated platelet-derived growth factor receptor-beta and its binding to class IA PI3K in vascular smooth muscle cells. |
| 3913 | 16569213 | PI3K (phosphoinositide 3-kinase) activity is involved in Ang (angiotensin) II-stimulated VSMC (vascular smooth muscle cell) growth and hypertrophy. |
| 3914 | 16569213 | In the present study, we demonstrate that the inhibition of PI3K in VSMCs by expression of a dominant-negative p85alpha mutant lacking the p110-binding domain (Deltap85), or by treatment of cells with LY294002, inhibited Ang II-stimulated PAI-1 (plasminogen activator inhibitor-1) mRNA expression. |
| 3915 | 16569213 | Using a GST (glutathione S-transferase) fusion protein containing the p85 N-terminal SH2 (Src homology 2) domain as 'bait' followed by MS/MS (tandem MS), we identified a 70 kDa fragment of the p70 PDGFR-beta (platelet-derived growth factor receptor-beta) as a signalling adapter that is phosphorylated and recruits the p85 subunit of PI3K after Ang II stimulation of AT1 (Ang II subtype 1) receptors on VSMCs. |
| 3916 | 16569213 | Stimulation of VSMCs with Ang II increased tyrosine-phosphorylation of p70 PDGFR-beta at Tyr751 and Tyr1021 and increased its binding to p85. |
| 3917 | 16569213 | PDGF also induced phosphorylation of p70 PDGFR-beta, a response inhibited by the PDGF tyrosine kinase selective inhibitor, AG1296. |
| 3918 | 16569213 | Ang II-stimulated phosphorylation of the p70 PDGFR-beta was blocked by the AT1 receptor antagonist, candesartan (CV 11974) and was partially inhibited by PP2 {4-amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine}, an Src family kinase inhibitor. |
| 3919 | 16569213 | Our result suggests that the p70 PDGFR-beta functions as an adapter that recruits PI3K to the membrane upon AT1 receptor stimulation. |
| 3920 | 16569213 | Angiotensin II stimulates phosphorylation of an ectodomain-truncated platelet-derived growth factor receptor-beta and its binding to class IA PI3K in vascular smooth muscle cells. |
| 3921 | 16569213 | PI3K (phosphoinositide 3-kinase) activity is involved in Ang (angiotensin) II-stimulated VSMC (vascular smooth muscle cell) growth and hypertrophy. |
| 3922 | 16569213 | In the present study, we demonstrate that the inhibition of PI3K in VSMCs by expression of a dominant-negative p85alpha mutant lacking the p110-binding domain (Deltap85), or by treatment of cells with LY294002, inhibited Ang II-stimulated PAI-1 (plasminogen activator inhibitor-1) mRNA expression. |
| 3923 | 16569213 | Using a GST (glutathione S-transferase) fusion protein containing the p85 N-terminal SH2 (Src homology 2) domain as 'bait' followed by MS/MS (tandem MS), we identified a 70 kDa fragment of the p70 PDGFR-beta (platelet-derived growth factor receptor-beta) as a signalling adapter that is phosphorylated and recruits the p85 subunit of PI3K after Ang II stimulation of AT1 (Ang II subtype 1) receptors on VSMCs. |
| 3924 | 16569213 | Stimulation of VSMCs with Ang II increased tyrosine-phosphorylation of p70 PDGFR-beta at Tyr751 and Tyr1021 and increased its binding to p85. |
| 3925 | 16569213 | PDGF also induced phosphorylation of p70 PDGFR-beta, a response inhibited by the PDGF tyrosine kinase selective inhibitor, AG1296. |
| 3926 | 16569213 | Ang II-stimulated phosphorylation of the p70 PDGFR-beta was blocked by the AT1 receptor antagonist, candesartan (CV 11974) and was partially inhibited by PP2 {4-amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine}, an Src family kinase inhibitor. |
| 3927 | 16569213 | Our result suggests that the p70 PDGFR-beta functions as an adapter that recruits PI3K to the membrane upon AT1 receptor stimulation. |
| 3928 | 16569213 | Angiotensin II stimulates phosphorylation of an ectodomain-truncated platelet-derived growth factor receptor-beta and its binding to class IA PI3K in vascular smooth muscle cells. |
| 3929 | 16569213 | PI3K (phosphoinositide 3-kinase) activity is involved in Ang (angiotensin) II-stimulated VSMC (vascular smooth muscle cell) growth and hypertrophy. |
| 3930 | 16569213 | In the present study, we demonstrate that the inhibition of PI3K in VSMCs by expression of a dominant-negative p85alpha mutant lacking the p110-binding domain (Deltap85), or by treatment of cells with LY294002, inhibited Ang II-stimulated PAI-1 (plasminogen activator inhibitor-1) mRNA expression. |
| 3931 | 16569213 | Using a GST (glutathione S-transferase) fusion protein containing the p85 N-terminal SH2 (Src homology 2) domain as 'bait' followed by MS/MS (tandem MS), we identified a 70 kDa fragment of the p70 PDGFR-beta (platelet-derived growth factor receptor-beta) as a signalling adapter that is phosphorylated and recruits the p85 subunit of PI3K after Ang II stimulation of AT1 (Ang II subtype 1) receptors on VSMCs. |
| 3932 | 16569213 | Stimulation of VSMCs with Ang II increased tyrosine-phosphorylation of p70 PDGFR-beta at Tyr751 and Tyr1021 and increased its binding to p85. |
| 3933 | 16569213 | PDGF also induced phosphorylation of p70 PDGFR-beta, a response inhibited by the PDGF tyrosine kinase selective inhibitor, AG1296. |
| 3934 | 16569213 | Ang II-stimulated phosphorylation of the p70 PDGFR-beta was blocked by the AT1 receptor antagonist, candesartan (CV 11974) and was partially inhibited by PP2 {4-amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine}, an Src family kinase inhibitor. |
| 3935 | 16569213 | Our result suggests that the p70 PDGFR-beta functions as an adapter that recruits PI3K to the membrane upon AT1 receptor stimulation. |
| 3936 | 16569213 | Angiotensin II stimulates phosphorylation of an ectodomain-truncated platelet-derived growth factor receptor-beta and its binding to class IA PI3K in vascular smooth muscle cells. |
| 3937 | 16569213 | PI3K (phosphoinositide 3-kinase) activity is involved in Ang (angiotensin) II-stimulated VSMC (vascular smooth muscle cell) growth and hypertrophy. |
| 3938 | 16569213 | In the present study, we demonstrate that the inhibition of PI3K in VSMCs by expression of a dominant-negative p85alpha mutant lacking the p110-binding domain (Deltap85), or by treatment of cells with LY294002, inhibited Ang II-stimulated PAI-1 (plasminogen activator inhibitor-1) mRNA expression. |
| 3939 | 16569213 | Using a GST (glutathione S-transferase) fusion protein containing the p85 N-terminal SH2 (Src homology 2) domain as 'bait' followed by MS/MS (tandem MS), we identified a 70 kDa fragment of the p70 PDGFR-beta (platelet-derived growth factor receptor-beta) as a signalling adapter that is phosphorylated and recruits the p85 subunit of PI3K after Ang II stimulation of AT1 (Ang II subtype 1) receptors on VSMCs. |
| 3940 | 16569213 | Stimulation of VSMCs with Ang II increased tyrosine-phosphorylation of p70 PDGFR-beta at Tyr751 and Tyr1021 and increased its binding to p85. |
| 3941 | 16569213 | PDGF also induced phosphorylation of p70 PDGFR-beta, a response inhibited by the PDGF tyrosine kinase selective inhibitor, AG1296. |
| 3942 | 16569213 | Ang II-stimulated phosphorylation of the p70 PDGFR-beta was blocked by the AT1 receptor antagonist, candesartan (CV 11974) and was partially inhibited by PP2 {4-amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine}, an Src family kinase inhibitor. |
| 3943 | 16569213 | Our result suggests that the p70 PDGFR-beta functions as an adapter that recruits PI3K to the membrane upon AT1 receptor stimulation. |
| 3944 | 16597691 | Recent data suggest that the phosphatidylinositol 3-kinase (PI3-K)/Akt/mammalian target of rapamycin (mTOR) pathway is important in diabetic nephropathy. |
| 3945 | 16597691 | It is interesting that D+SRL was associated with a significant reduction of renal TGF-beta1 and glomerular connective tissue growth factor. |
| 3946 | 16598903 | The two main transduction pathways are the phosphatidylinositol 3 kinase pathway activating protein kinase B which is involved in priority in metabolic effects, and the MAP kinase pathway involved in nuclear effects, proliferation and differentiation. |
| 3947 | 16598903 | This phosphorylation is activated in response to different signals involved in insulin resistance, hyperinsulinism, TNFalpha or increased free fatty acids from adipose tissue, which are transformed inside the cell in acyl-CoA. |
| 3948 | 16618833 | Phosphatidylinositol 3-kinase-dependent insulin-signaling pathways in endothelium related to production of NO share striking similarities with metabolic pathways in skeletal muscle that promote glucose uptake. |
| 3949 | 16618833 | Other distinct nonmetabolic branches of insulin-signaling pathways regulate secretion of the vasoconstrictor endothelin-1 in endothelium. |
| 3950 | 16618833 | Metabolic insulin resistance is characterized by pathway-specific impairment in phosphatidylinositol 3-kinase-dependent signaling, which in endothelium may cause imbalance between production of NO and secretion of endothelin-1, leading to decreased blood flow, which worsens insulin resistance. |
| 3951 | 16618833 | Phosphatidylinositol 3-kinase-dependent insulin-signaling pathways in endothelium related to production of NO share striking similarities with metabolic pathways in skeletal muscle that promote glucose uptake. |
| 3952 | 16618833 | Other distinct nonmetabolic branches of insulin-signaling pathways regulate secretion of the vasoconstrictor endothelin-1 in endothelium. |
| 3953 | 16618833 | Metabolic insulin resistance is characterized by pathway-specific impairment in phosphatidylinositol 3-kinase-dependent signaling, which in endothelium may cause imbalance between production of NO and secretion of endothelin-1, leading to decreased blood flow, which worsens insulin resistance. |
| 3954 | 16622294 | Insulin-resistant muscle has defects at several steps of the insulin-signaling pathway, including decreases in insulin-stimulated insulin receptor and insulin receptor substrate-1 tyrosine phosphorylation, and phosphatidylinositol 3-kinase (PI 3-kinase) activation. |
| 3955 | 16622294 | Weight loss and thiazolidinediones (TZDs) improve glucose disposal, in part, by increasing insulin-stimulated insulin receptor and IRS-1 tyrosine phosphorylation and PI 3-kinase activity. |
| 3956 | 16622294 | A novel approach to reverse insulin resistance involves inhibition of the stress-activated protein kinase Jun N-terminal kinase (JNK) and the protein tyrosine phosphatases (PTPs). |
| 3957 | 16622294 | AMPK activation is also involved in the mechanism of action of metformin and adiponectin. |
| 3958 | 16634987 | Insulin increases gelatinase activity in rat glomerular mesangial cells via ERK- and PI-3 kinase-dependent signalling. |
| 3959 | 16634987 | Furthermore, we show using the specific inhibitors LY294002 and PD98059 that insulin induced increased gelatinase activity via an intracellular signalling mechanism involving phosphatidylinositol-3 kinase (PI-3K) and the extracellular signal-regulated kinase 1/2 (ERK1/2) mitogen-activated protein kinases (MAPKs) respectively. |
| 3960 | 16634987 | In addition, we demonstrate that PI-3 kinase and ERK1/2 MAPK are activated by insulin in GMCs. |
| 3961 | 16644672 | The glucoincretin hormone glucagon-like peptide-1 (GLP-1) increases pancreatic beta-cell proliferation and survival through sequential activation of the epidermal growth factor receptor (EGFR), phosphatidylinositol-3 kinase (PI 3-kinase), and Akt. |
| 3962 | 16644672 | GLP-1 inhibited FoxO1 through phosphorylation-dependent nuclear exclusion in pancreatic beta (INS832/13) cells. |
| 3963 | 16644672 | The effect of GLP-1 was suppressed by inhibitors of EGFR (AG1478) and PI 3-kinase (LY294002). |
| 3964 | 16644672 | Gene expression and chromatin immunoprecipitation assays demonstrated that GLP-1 increases pancreatic and duodenal homeobox gene-1 and Foxa2 expression and inhibits FoxO1 binding to both promoters. |
| 3965 | 16644688 | Intestinal insulin resistance and aberrant production of apolipoprotein B48 lipoproteins in an animal model of insulin resistance and metabolic dyslipidemia: evidence for activation of protein tyrosine phosphatase-1B, extracellular signal-related kinase, and sterol regulatory element-binding protein-1c in the fructose-fed hamster intestine. |
| 3966 | 16644688 | Intestinal lipoprotein production in chow-fed hamsters was responsive to the inhibitory effects of insulin, and a decrease in circulating levels of triglyceride-rich apolipoprotein (apo)B48-containing lipoproteins occurred 60 min after insulin administration. |
| 3967 | 16644688 | However, fructose-fed hamster intestine was not responsive to the insulin-induced downregulation of apoB48-lipoprotein production, suggesting insulin insensitivity at the level of the intestine. |
| 3968 | 16644688 | Enterocytes from the fructose-fed hamster exhibited normal activity of the insulin receptor but reduced levels of insulin receptor substrate-1 phosphorylation and mass and Akt protein mass. |
| 3969 | 16644688 | Conversely, the protein mass of the p110 subunit of phosphatidylinositol 3-kinase, protein tyrosine phosphatase-1B, and basal levels of phosphorylated extracellular signal-related kinase (ERK) were significantly increased in the fructose-fed hamster intestine. |
| 3970 | 16644688 | Modulating the ERK pathway through in vivo inhibition of mitogen-activated protein/ERK kinase 1/2, the upstream activator of ERK1/2, we observed a significant decrease in intestinal apoB48 synthesis and secretion. |
| 3971 | 16644688 | Interestingly, enhanced basal ERK activity in the fructose-fed hamster intestine was accompanied by an increased activation of sterol regulatory element-binding protein. |
| 3972 | 16644688 | In summary, these data suggest that insulin insensitivity at the level of the intestine and aberrant insulin signaling are important underlying factors in intestinal overproduction of highly atherogenic apoB48-containing lipoproteins in the insulin-resistant state. |
| 3973 | 16644688 | Basal activation of the ERK pathway may be an important contributor to the aberrant insulin signaling and lipoprotein overproduction in this model. |
| 3974 | 16644687 | We tested the hypothesis that phosphatidylinositol 3-kinase (PI 3-kinase)-dependent activation of Akt is essential for the expression of cardiac heat-shock protein 72 (HSP72) and that this pathway is impaired in the streptozotocin (STZ)-induced diabetic heart. |
| 3975 | 16644687 | Compared with control heart, hyperthermia-induced HSP72 expression and phosphorylation of Akt were attenuated in the STZ-vehicle heart. |
| 3976 | 16644687 | Pretreatment with wortmannin attenuated hyperthermia-induced HSP72 expression and phosphorylation of Akt. |
| 3977 | 16644687 | Insulin treatment restored HSP72 expression and reperfusion-induced functional recovery. |
| 3978 | 16644687 | In cultured neonatal rat cardiomyocytes, hyperthermia-induced HSP72 expression was enhanced by insulin, together with tolerance against hypoxia-reoxygenation injury. |
| 3979 | 16644687 | Wortmannin and LY294002 inhibited hyperthermia-induced HSP72 expression and phosphorylation of Akt. |
| 3980 | 16644687 | Our results indicate that activation of Akt, in a PI 3-kinase-dependent manner, is essential for hyperthermia-induced HSP72 expression in association with cardioprotection, suggesting impairment of this signaling pathway in the STZ-induced diabetic heart, probably due to insulin deficiency. |
| 3981 | 16679293 | Loss of class IA PI3K signaling in muscle leads to impaired muscle growth, insulin response, and hyperlipidemia. |
| 3982 | 16679293 | The evolutionarily conserved phosphoinositide 3-kinase (PI3K) signaling pathway mediates both the metabolic effects of insulin and the growth-promoting effects of insulin-like growth factor-1 (IGF-1). |
| 3983 | 16679293 | We have generated mice deficient in both the p85alpha/p55alpha/p50alpha and the p85beta regulatory subunits of class I(A) PI3K in skeletal muscles. |
| 3984 | 16679293 | These results demonstrate that in vivo p85 is a critical mediator of class I(A) PI3K signaling in the regulation of muscle growth and metabolism. |
| 3985 | 16679293 | Loss of class IA PI3K signaling in muscle leads to impaired muscle growth, insulin response, and hyperlipidemia. |
| 3986 | 16679293 | The evolutionarily conserved phosphoinositide 3-kinase (PI3K) signaling pathway mediates both the metabolic effects of insulin and the growth-promoting effects of insulin-like growth factor-1 (IGF-1). |
| 3987 | 16679293 | We have generated mice deficient in both the p85alpha/p55alpha/p50alpha and the p85beta regulatory subunits of class I(A) PI3K in skeletal muscles. |
| 3988 | 16679293 | These results demonstrate that in vivo p85 is a critical mediator of class I(A) PI3K signaling in the regulation of muscle growth and metabolism. |
| 3989 | 16679293 | Loss of class IA PI3K signaling in muscle leads to impaired muscle growth, insulin response, and hyperlipidemia. |
| 3990 | 16679293 | The evolutionarily conserved phosphoinositide 3-kinase (PI3K) signaling pathway mediates both the metabolic effects of insulin and the growth-promoting effects of insulin-like growth factor-1 (IGF-1). |
| 3991 | 16679293 | We have generated mice deficient in both the p85alpha/p55alpha/p50alpha and the p85beta regulatory subunits of class I(A) PI3K in skeletal muscles. |
| 3992 | 16679293 | These results demonstrate that in vivo p85 is a critical mediator of class I(A) PI3K signaling in the regulation of muscle growth and metabolism. |
| 3993 | 16679293 | Loss of class IA PI3K signaling in muscle leads to impaired muscle growth, insulin response, and hyperlipidemia. |
| 3994 | 16679293 | The evolutionarily conserved phosphoinositide 3-kinase (PI3K) signaling pathway mediates both the metabolic effects of insulin and the growth-promoting effects of insulin-like growth factor-1 (IGF-1). |
| 3995 | 16679293 | We have generated mice deficient in both the p85alpha/p55alpha/p50alpha and the p85beta regulatory subunits of class I(A) PI3K in skeletal muscles. |
| 3996 | 16679293 | These results demonstrate that in vivo p85 is a critical mediator of class I(A) PI3K signaling in the regulation of muscle growth and metabolism. |
| 3997 | 16679292 | Although the class I(A) phosphoinositide 3-kinase (PI3K) pathway is central to the metabolic actions of insulin, its mechanism of action is not well understood. |
| 3998 | 16679292 | To identify the role of the PI3K pathway in insulin regulation of hepatic function, we ablated the expression of both major regulatory subunits of PI3K by crossing mice lacking Pik3r1 in liver with Pik3r2 null mice, creating liver-specific double knockout mice (L-p85DKO). |
| 3999 | 16679292 | L-p85DKO mice failed to activate PI3K or generate PIP(3) upon insulin stimulation or activate its two major effectors, Akt and PKClambda/xi. |
| 4000 | 16679292 | Decreased Akt activation resulted in increased gluconeogenic gene expression, impaired glucose tolerance, and hyperinsulinemia, while the defective activation of PKClambda/xi by insulin was associated with hypolipidemia and decreased transcription of SREBP-1c. |
| 4001 | 16679292 | These data indicate that the PI3K pathway is critical for insulin's actions in the liver in vivo, and that differential regulation by Akt and PKClambda/xi differentially defines specific actions of insulin and PI3K on hepatic glucose and lipid metabolism. |
| 4002 | 16679292 | Although the class I(A) phosphoinositide 3-kinase (PI3K) pathway is central to the metabolic actions of insulin, its mechanism of action is not well understood. |
| 4003 | 16679292 | To identify the role of the PI3K pathway in insulin regulation of hepatic function, we ablated the expression of both major regulatory subunits of PI3K by crossing mice lacking Pik3r1 in liver with Pik3r2 null mice, creating liver-specific double knockout mice (L-p85DKO). |
| 4004 | 16679292 | L-p85DKO mice failed to activate PI3K or generate PIP(3) upon insulin stimulation or activate its two major effectors, Akt and PKClambda/xi. |
| 4005 | 16679292 | Decreased Akt activation resulted in increased gluconeogenic gene expression, impaired glucose tolerance, and hyperinsulinemia, while the defective activation of PKClambda/xi by insulin was associated with hypolipidemia and decreased transcription of SREBP-1c. |
| 4006 | 16679292 | These data indicate that the PI3K pathway is critical for insulin's actions in the liver in vivo, and that differential regulation by Akt and PKClambda/xi differentially defines specific actions of insulin and PI3K on hepatic glucose and lipid metabolism. |
| 4007 | 16679292 | Although the class I(A) phosphoinositide 3-kinase (PI3K) pathway is central to the metabolic actions of insulin, its mechanism of action is not well understood. |
| 4008 | 16679292 | To identify the role of the PI3K pathway in insulin regulation of hepatic function, we ablated the expression of both major regulatory subunits of PI3K by crossing mice lacking Pik3r1 in liver with Pik3r2 null mice, creating liver-specific double knockout mice (L-p85DKO). |
| 4009 | 16679292 | L-p85DKO mice failed to activate PI3K or generate PIP(3) upon insulin stimulation or activate its two major effectors, Akt and PKClambda/xi. |
| 4010 | 16679292 | Decreased Akt activation resulted in increased gluconeogenic gene expression, impaired glucose tolerance, and hyperinsulinemia, while the defective activation of PKClambda/xi by insulin was associated with hypolipidemia and decreased transcription of SREBP-1c. |
| 4011 | 16679292 | These data indicate that the PI3K pathway is critical for insulin's actions in the liver in vivo, and that differential regulation by Akt and PKClambda/xi differentially defines specific actions of insulin and PI3K on hepatic glucose and lipid metabolism. |
| 4012 | 16679292 | Although the class I(A) phosphoinositide 3-kinase (PI3K) pathway is central to the metabolic actions of insulin, its mechanism of action is not well understood. |
| 4013 | 16679292 | To identify the role of the PI3K pathway in insulin regulation of hepatic function, we ablated the expression of both major regulatory subunits of PI3K by crossing mice lacking Pik3r1 in liver with Pik3r2 null mice, creating liver-specific double knockout mice (L-p85DKO). |
| 4014 | 16679292 | L-p85DKO mice failed to activate PI3K or generate PIP(3) upon insulin stimulation or activate its two major effectors, Akt and PKClambda/xi. |
| 4015 | 16679292 | Decreased Akt activation resulted in increased gluconeogenic gene expression, impaired glucose tolerance, and hyperinsulinemia, while the defective activation of PKClambda/xi by insulin was associated with hypolipidemia and decreased transcription of SREBP-1c. |
| 4016 | 16679292 | These data indicate that the PI3K pathway is critical for insulin's actions in the liver in vivo, and that differential regulation by Akt and PKClambda/xi differentially defines specific actions of insulin and PI3K on hepatic glucose and lipid metabolism. |
| 4017 | 16687120 | During the past decade, the control of translation initiation by the PI3K/Akt/mTOR pathway in the development of these pathologies has been documented. |
| 4018 | 16731820 | Glucose controls islet beta-cell mass and function at least in part through the phosphatidylinositol 3-kinase (PI3K)/Akt pathway downstream of insulin signaling. |
| 4019 | 16731823 | Mercury increased PI3K activity and its downstream effector Akt phosphorylation. |
| 4020 | 16731823 | Antioxidant N-acetyl-l-cysteine (NAC) prevented mercury-induced insulin secretion inhibition and Akt phosphorylation but not increased PI3K activity. |
| 4021 | 16731823 | Inhibition of PI3K/Akt activity with PI3K inhibitor or by expressing the dominant-negative p85 or Akt prevented mercury-induced insulin secretion inhibition but not ROS production. |
| 4022 | 16731823 | These results indicate that both PI3K and ROS independently regulated Akt signaling-related, mercury-induced insulin secretion inhibition. |
| 4023 | 16731823 | These results demonstrate that low-dose mercury-induced oxidative stress and PI3K activation cause Akt signaling-related pancreatic beta-cell dysfunction. |
| 4024 | 16731823 | Mercury increased PI3K activity and its downstream effector Akt phosphorylation. |
| 4025 | 16731823 | Antioxidant N-acetyl-l-cysteine (NAC) prevented mercury-induced insulin secretion inhibition and Akt phosphorylation but not increased PI3K activity. |
| 4026 | 16731823 | Inhibition of PI3K/Akt activity with PI3K inhibitor or by expressing the dominant-negative p85 or Akt prevented mercury-induced insulin secretion inhibition but not ROS production. |
| 4027 | 16731823 | These results indicate that both PI3K and ROS independently regulated Akt signaling-related, mercury-induced insulin secretion inhibition. |
| 4028 | 16731823 | These results demonstrate that low-dose mercury-induced oxidative stress and PI3K activation cause Akt signaling-related pancreatic beta-cell dysfunction. |
| 4029 | 16731823 | Mercury increased PI3K activity and its downstream effector Akt phosphorylation. |
| 4030 | 16731823 | Antioxidant N-acetyl-l-cysteine (NAC) prevented mercury-induced insulin secretion inhibition and Akt phosphorylation but not increased PI3K activity. |
| 4031 | 16731823 | Inhibition of PI3K/Akt activity with PI3K inhibitor or by expressing the dominant-negative p85 or Akt prevented mercury-induced insulin secretion inhibition but not ROS production. |
| 4032 | 16731823 | These results indicate that both PI3K and ROS independently regulated Akt signaling-related, mercury-induced insulin secretion inhibition. |
| 4033 | 16731823 | These results demonstrate that low-dose mercury-induced oxidative stress and PI3K activation cause Akt signaling-related pancreatic beta-cell dysfunction. |
| 4034 | 16731823 | Mercury increased PI3K activity and its downstream effector Akt phosphorylation. |
| 4035 | 16731823 | Antioxidant N-acetyl-l-cysteine (NAC) prevented mercury-induced insulin secretion inhibition and Akt phosphorylation but not increased PI3K activity. |
| 4036 | 16731823 | Inhibition of PI3K/Akt activity with PI3K inhibitor or by expressing the dominant-negative p85 or Akt prevented mercury-induced insulin secretion inhibition but not ROS production. |
| 4037 | 16731823 | These results indicate that both PI3K and ROS independently regulated Akt signaling-related, mercury-induced insulin secretion inhibition. |
| 4038 | 16731823 | These results demonstrate that low-dose mercury-induced oxidative stress and PI3K activation cause Akt signaling-related pancreatic beta-cell dysfunction. |
| 4039 | 16731823 | Mercury increased PI3K activity and its downstream effector Akt phosphorylation. |
| 4040 | 16731823 | Antioxidant N-acetyl-l-cysteine (NAC) prevented mercury-induced insulin secretion inhibition and Akt phosphorylation but not increased PI3K activity. |
| 4041 | 16731823 | Inhibition of PI3K/Akt activity with PI3K inhibitor or by expressing the dominant-negative p85 or Akt prevented mercury-induced insulin secretion inhibition but not ROS production. |
| 4042 | 16731823 | These results indicate that both PI3K and ROS independently regulated Akt signaling-related, mercury-induced insulin secretion inhibition. |
| 4043 | 16731823 | These results demonstrate that low-dose mercury-induced oxidative stress and PI3K activation cause Akt signaling-related pancreatic beta-cell dysfunction. |
| 4044 | 16735449 | This secretion was blocked by synthetic fatty acids and by inhibition of phosphatidylinositol 3-kinase or Akt. |
| 4045 | 16735449 | In conclusion, release of the insulin-mimetic visfatin may represent a major mechanism of metabolic TZD action. |
| 4046 | 16738317 | PTEN (phosphatase with tensin homology) is a potent negative regulator of phosphoinositide 3-kinase (PI3K)/Akt signaling, an evolutionarily conserved pathway that signals downstream of growth factors, including insulin and insulin-like growth factor 1. |
| 4047 | 16738317 | The specific regulatory elements of the PI3K pathway in these insulin-expressing tissues that contribute to growth and metabolism in higher organisms are unknown. |
| 4048 | 16738317 | Here, we report PTEN as a critical determinant of body size and glucose metabolism when targeting is driven by the rat insulin promoter in mice. |
| 4049 | 16738317 | The partial deletion of PTEN in the hypothalamus resulted in significant whole-body growth restriction and increased insulin sensitivity. |
| 4050 | 16738317 | Parallel enhancement in PI3K signaling was found in PTEN-deficient hypothalamus and beta cells. |
| 4051 | 16738317 | Together, we have shown that PTEN in insulin-transcribing cells may play an integrative role in regulating growth and metabolism in vivo. |
| 4052 | 16738317 | PTEN (phosphatase with tensin homology) is a potent negative regulator of phosphoinositide 3-kinase (PI3K)/Akt signaling, an evolutionarily conserved pathway that signals downstream of growth factors, including insulin and insulin-like growth factor 1. |
| 4053 | 16738317 | The specific regulatory elements of the PI3K pathway in these insulin-expressing tissues that contribute to growth and metabolism in higher organisms are unknown. |
| 4054 | 16738317 | Here, we report PTEN as a critical determinant of body size and glucose metabolism when targeting is driven by the rat insulin promoter in mice. |
| 4055 | 16738317 | The partial deletion of PTEN in the hypothalamus resulted in significant whole-body growth restriction and increased insulin sensitivity. |
| 4056 | 16738317 | Parallel enhancement in PI3K signaling was found in PTEN-deficient hypothalamus and beta cells. |
| 4057 | 16738317 | Together, we have shown that PTEN in insulin-transcribing cells may play an integrative role in regulating growth and metabolism in vivo. |
| 4058 | 16738317 | PTEN (phosphatase with tensin homology) is a potent negative regulator of phosphoinositide 3-kinase (PI3K)/Akt signaling, an evolutionarily conserved pathway that signals downstream of growth factors, including insulin and insulin-like growth factor 1. |
| 4059 | 16738317 | The specific regulatory elements of the PI3K pathway in these insulin-expressing tissues that contribute to growth and metabolism in higher organisms are unknown. |
| 4060 | 16738317 | Here, we report PTEN as a critical determinant of body size and glucose metabolism when targeting is driven by the rat insulin promoter in mice. |
| 4061 | 16738317 | The partial deletion of PTEN in the hypothalamus resulted in significant whole-body growth restriction and increased insulin sensitivity. |
| 4062 | 16738317 | Parallel enhancement in PI3K signaling was found in PTEN-deficient hypothalamus and beta cells. |
| 4063 | 16738317 | Together, we have shown that PTEN in insulin-transcribing cells may play an integrative role in regulating growth and metabolism in vivo. |
| 4064 | 16753575 | Nutrient overload, insulin resistance, and ribosomal protein S6 kinase 1, S6K1. |
| 4065 | 16753575 | Recent studies have revealed that ribosomal protein S6 kinase 1, S6K1, an effector of mTOR, is sensitive to both insulin and nutrients, including amino acids. |
| 4066 | 16753575 | Although S6K1 is an effector of growth, recent reports show that amino acids also negatively affect insulin signaling through mTOR/S6K1 phosphorylation of IRS1. |
| 4067 | 16753575 | Moreover, rather than signaling through the class 1 PI3K pathway, amino acids appear to mediate mTOR activation through class 3 PI3K, or hVps34. |
| 4068 | 16753575 | Consistent with this, infusion of amino acids into humans leads to S6K1 activation, inhibition of insulin-induced class 1 PI3K activation, and insulin resistance. |
| 4069 | 16753575 | Thus, S6K1 may mediate deleterious effects, like insulin resistance, and potentially type 2 diabetes in the face of nutrient excess. |
| 4070 | 16753575 | Nutrient overload, insulin resistance, and ribosomal protein S6 kinase 1, S6K1. |
| 4071 | 16753575 | Recent studies have revealed that ribosomal protein S6 kinase 1, S6K1, an effector of mTOR, is sensitive to both insulin and nutrients, including amino acids. |
| 4072 | 16753575 | Although S6K1 is an effector of growth, recent reports show that amino acids also negatively affect insulin signaling through mTOR/S6K1 phosphorylation of IRS1. |
| 4073 | 16753575 | Moreover, rather than signaling through the class 1 PI3K pathway, amino acids appear to mediate mTOR activation through class 3 PI3K, or hVps34. |
| 4074 | 16753575 | Consistent with this, infusion of amino acids into humans leads to S6K1 activation, inhibition of insulin-induced class 1 PI3K activation, and insulin resistance. |
| 4075 | 16753575 | Thus, S6K1 may mediate deleterious effects, like insulin resistance, and potentially type 2 diabetes in the face of nutrient excess. |
| 4076 | 16794223 | Phosphatidylinositol-3-kinase regulates scavenger receptor class B type I subcellular localization and selective lipid uptake in hepatocytes. |
| 4077 | 16803868 | Enigma interacts with adaptor protein with PH and SH2 domains to control insulin-induced actin cytoskeleton remodeling and glucose transporter 4 translocation. |
| 4078 | 16803868 | APS (adaptor protein with PH and SH2 domains) initiates a phosphatidylinositol 3-kinase-independent pathway involved in insulin-stimulated glucose transport. |
| 4079 | 16803868 | We recently identified Enigma, a PDZ and LIM domain-containing protein, as a partner of APS and showed that APS-Enigma complex plays a critical role in actin cytoskeleton organization in fibroblastic cells. |
| 4080 | 16803868 | Because actin rearrangement is important for insulin-induced glucose transporter 4 (Glut 4) translocation, we studied the potential involvement of Enigma in insulin-induced glucose transport in 3T3-L1 adipocytes. |
| 4081 | 16803868 | Expression of an APS mutant unable to bind Enigma increased the insulin-induced Glut 4 translocation to the plasma membrane. |
| 4082 | 16803868 | Using time-lapse fluorescent microscopy of green fluorescent protein-actin, we demonstrated that the overexpression of Enigma altered insulin-induced actin rearrangements, whereas the expression of Enigma without its LIM domains was without effect. |
| 4083 | 16803868 | Taken together, these data strongly suggest that the interaction between APS and Enigma is involved in insulin-induced Glut 4 translocation by regulating cortical actin remodeling and raise the possibility that modification of APS/Enigma ratio could participate in the alteration of insulin-induced glucose uptake in adipose tissue. |
| 4084 | 16804076 | Stimulation of cellular glucose uptake involves phosphatidylinositide-3-kinase (PI-3K)-dependent activation of protein kinase B/Akt. |
| 4085 | 16804076 | A further kinase downstream of PI-3K is serum- and glucocorticoid-inducible kinase (SGK)1, which is upregulated by mineralocorticoids and, thus, downregulated by salt intake. |
| 4086 | 16804076 | Stimulation of cellular glucose uptake involves phosphatidylinositide-3-kinase (PI-3K)-dependent activation of protein kinase B/Akt. |
| 4087 | 16804076 | A further kinase downstream of PI-3K is serum- and glucocorticoid-inducible kinase (SGK)1, which is upregulated by mineralocorticoids and, thus, downregulated by salt intake. |
| 4088 | 16804083 | Gene disruption of the tumor suppressor PTEN, a negative regulator of the phosphatidylinositol 3-kinase/Akt pathway, in fruit flies and mice demonstrated its role in size control in a cell-specific manner. |
| 4089 | 16804083 | We link early renal hypertrophy with significant reduction in PTEN expression in the streptozotocin-induced diabetic kidney cortex and glomeruli, concomitant with activation of Akt. |
| 4090 | 16804083 | Similarly, exposure of mesangial cells to high concentrations of glucose also decreased PTEN expression and its phosphatase activity, resulting in increased Akt activity. |
| 4091 | 16804083 | TGF-beta significantly reduced PTEN expression in mesangial cells, with a reduction in its phosphatase activity and an increase in Akt activation. |
| 4092 | 16804083 | PTEN and dominant-negative Akt attenuated TGF-beta-induced hypertrophy of mesangial cells. |
| 4093 | 16804083 | Finally, we show that inhibition of TGF-beta signal transduction blocks the effect of high glucose on PTEN downregulation. |
| 4094 | 16804083 | These data identify a novel mechanism placing PTEN as a key regulator of diabetic mesangial hypertrophy involving TGF-beta signaling. |
| 4095 | 16807405 | Chronic inhibition of mammalian target of rapamycin signaling downregulates insulin receptor substrates 1 and 2 and AKT activation: A crossroad between cancer and diabetes? |
| 4096 | 16807405 | Overactivation of the mammalian target of rapamycin (mTOR) branch downstream of the phosphatidylinositol 3-kinase-AKT pathway critically modulates insulin and growth factor signaling by insulin receptor substrates (IRS). |
| 4097 | 16807405 | In view of the critical role of AKT in insulin signaling and tumorigenesis, the in vivo expression and activation of this kinase and of IRS-1 and IRS-2 were explored in PBMC of 30 patients who were treated long term with rapamycin. |
| 4098 | 16807405 | A marked decrease of basal and insulin-stimulated AKT phosphorylation, which correlated with the increase of patients' insulin resistance, and a significant increase of IRS total protein expression, together with a lower (IRS-2) or absent (IRS-1) increase of insulin-induced tyrosine phosphorylation, were found. |
| 4099 | 16828931 | Insulin was perfused with and without an inhibitor for tyrosine kinase or phosphatidylinositol 3-kinase (PI 3-kinase). |
| 4100 | 16828931 | These results suggest that insulin stimulates the release of ANP through PI 3-kinase and tyrosine kinase, and augmentation of insulin-stimulated ANP release in diabetic rat atria may be partly due to an upregulation of insulin receptor. |
| 4101 | 16839840 | Insulin-stimulated insulin receptor substrate-2-associated phosphatidylinositol 3-kinase activity is enhanced in human skeletal muscle after exercise. |
| 4102 | 16839840 | In mouse skeletal muscle, prior exercise enhances insulin-stimulated insulin receptor substrate-2 (IRS-2) signaling (Diabetes 2002;51:479-83), but it is unknown if this also occurs in humans. |
| 4103 | 16839840 | Insulin increased (P < .05) Akt Ser473 and GSK-3alpha/beta Ser21/Ser9 phosphorylation in both trials, with the response tending to be higher in the exercise trial. |
| 4104 | 16839840 | In conclusion, in the immediate period after an acute bout of exercise, insulin-stimulated IRS-2 signaling is enhanced in human skeletal muscle. |
| 4105 | 16839860 | Insulin mediates its action on target organs through phosphorylation of a transmembrane-spanning tyrosine kinase receptor, the insulin receptor (IR). |
| 4106 | 16839860 | In particular, phosphorylation of IRS-1 on serine Ser612 causes dissociation of the p85 subunit of phosphatidylinositol 3-kinase, inhibiting further signaling. |
| 4107 | 16839860 | Dysregulation of sympathetic nervous and renin-angiotensin systems resulting in enhanced stimulation of both adrenergic and angiotensin II receptors is a typical feature of several cardiovascular diseases and, at the same time, is involved in the pathogenesis of insulin resistance. |
| 4108 | 16842543 | Melatonin stimulates glucose transport via insulin receptor substrate-1/phosphatidylinositol 3-kinase pathway in C2C12 murine skeletal muscle cells. |
| 4109 | 16842543 | However, 3',5'-cyclic adenosine monophosphate-activated protein kinase (AMPK), another important glucose transport stimulatory mediator via an insulin-independent pathway, was not influenced by melatonin treatment. |
| 4110 | 16842543 | Activity of p38 mitogen-activated protein kinase (MAPK), a downstream mediator of AMPK, was also not changed by melatonin. |
| 4111 | 16870142 | Insulin suppressed angptl4 mRNA expression in time- and dose-dependent manners, and the inhibitory effect was attenuated by a RNA synthesis inhibitor actinomycin D and a phosphoinositide 3-kinase (PI3K) inhibitor LY294002. |
| 4112 | 16870142 | Adenoviral-mediated overexpression of forkhead transcription factor Foxo1 increased angptl4 mRNA expression, and insulin significantly suppressed its effect. |
| 4113 | 16870142 | In addition, insulin failed to decrease angptl4 mRNA expression in an insulin-resistant state induced by TNF-alpha in 3T3-L1 adipocytes. |
| 4114 | 16870142 | These results suggest that insulin downregulates angptl4 mRNA expression via PI3K/Foxo1 pathway in 3T3-L1 adipocytes, and that the reduction of angptl4 mRNA by insulin is attenuated in insulin resistance. |
| 4115 | 16870142 | Insulin suppressed angptl4 mRNA expression in time- and dose-dependent manners, and the inhibitory effect was attenuated by a RNA synthesis inhibitor actinomycin D and a phosphoinositide 3-kinase (PI3K) inhibitor LY294002. |
| 4116 | 16870142 | Adenoviral-mediated overexpression of forkhead transcription factor Foxo1 increased angptl4 mRNA expression, and insulin significantly suppressed its effect. |
| 4117 | 16870142 | In addition, insulin failed to decrease angptl4 mRNA expression in an insulin-resistant state induced by TNF-alpha in 3T3-L1 adipocytes. |
| 4118 | 16870142 | These results suggest that insulin downregulates angptl4 mRNA expression via PI3K/Foxo1 pathway in 3T3-L1 adipocytes, and that the reduction of angptl4 mRNA by insulin is attenuated in insulin resistance. |
| 4119 | 16880201 | A role for 14-3-3 in insulin-stimulated GLUT4 translocation through its interaction with the RabGAP AS160. |
| 4120 | 16880201 | Translocation of the insulin-regulated glucose transporter GLUT4 to the cell surface is dependent on the phosphatidylinositol 3-kinase/Akt pathway. |
| 4121 | 16880201 | The RabGAP (Rab GTPase-activating protein) AS160 (Akt substrate of 160 kDa) is a direct substrate of Akt and plays an essential role in the regulation of GLUT4 trafficking. |
| 4122 | 16880201 | We have used liquid chromatography tandem mass spectrometry to identify several 14-3-3 isoforms as AS160-interacting proteins. 14-3-3 proteins interact with AS160 in an insulin- and Akt-dependent manner via an Akt phosphorylation site, Thr-642. |
| 4123 | 16880201 | This correlates with the dominant negative effect of both the AS160(T642A) and the AS160(4P) mutants on insulin-stimulated GLUT4 translocation. |
| 4124 | 16880201 | Introduction of a constitutive 14-3-3 binding site into AS160(4P) restored 14-3-3 binding without disrupting AS160-IRAP (insulin-responsive amino peptidase) interaction and reversed the inhibitory effect of AS160(4P) on GLUT4 translocation. |
| 4125 | 16880201 | These data show that the insulin-dependent association of 14-3-3 with AS160 plays an important role in GLUT4 trafficking in adipocytes. |
| 4126 | 16880400 | Phosphoinositide 3-kinase regulatory subunit p85alpha suppresses insulin action via positive regulation of PTEN. |
| 4127 | 16880400 | The phosphoinositide 3-kinase (PI3K) pathway is central to the metabolic actions of insulin on liver. |
| 4128 | 16880400 | Here, we show that mice with a liver-specific deletion of the p85alpha regulatory subunit of PI3K (L-Pik3r1KO) exhibit a paradoxical improvement of hepatic and peripheral insulin sensitivity. |
| 4129 | 16880400 | Although PI3K enzymatic activity is diminished in L-Pik3r1KO livers because of a reduced level of regulatory and catalytic subunits of PI3K, insulin-stimulated Akt activity is actually increased. |
| 4130 | 16880400 | This increased Akt activity correlates with increased phosphatidylinositol (3,4,5)-trisphosphate levels which are due, at least in part, to diminished activity of the (3,4,5)-trisphosphate phosphatase PTEN. |
| 4131 | 16880400 | Thus, the regulatory subunit p85alpha is a critical modulator of insulin sensitivity in vivo not only because of its effects on PI3K activation, but also as a regulator of PTEN activity. |
| 4132 | 16880400 | Phosphoinositide 3-kinase regulatory subunit p85alpha suppresses insulin action via positive regulation of PTEN. |
| 4133 | 16880400 | The phosphoinositide 3-kinase (PI3K) pathway is central to the metabolic actions of insulin on liver. |
| 4134 | 16880400 | Here, we show that mice with a liver-specific deletion of the p85alpha regulatory subunit of PI3K (L-Pik3r1KO) exhibit a paradoxical improvement of hepatic and peripheral insulin sensitivity. |
| 4135 | 16880400 | Although PI3K enzymatic activity is diminished in L-Pik3r1KO livers because of a reduced level of regulatory and catalytic subunits of PI3K, insulin-stimulated Akt activity is actually increased. |
| 4136 | 16880400 | This increased Akt activity correlates with increased phosphatidylinositol (3,4,5)-trisphosphate levels which are due, at least in part, to diminished activity of the (3,4,5)-trisphosphate phosphatase PTEN. |
| 4137 | 16880400 | Thus, the regulatory subunit p85alpha is a critical modulator of insulin sensitivity in vivo not only because of its effects on PI3K activation, but also as a regulator of PTEN activity. |
| 4138 | 16880400 | Phosphoinositide 3-kinase regulatory subunit p85alpha suppresses insulin action via positive regulation of PTEN. |
| 4139 | 16880400 | The phosphoinositide 3-kinase (PI3K) pathway is central to the metabolic actions of insulin on liver. |
| 4140 | 16880400 | Here, we show that mice with a liver-specific deletion of the p85alpha regulatory subunit of PI3K (L-Pik3r1KO) exhibit a paradoxical improvement of hepatic and peripheral insulin sensitivity. |
| 4141 | 16880400 | Although PI3K enzymatic activity is diminished in L-Pik3r1KO livers because of a reduced level of regulatory and catalytic subunits of PI3K, insulin-stimulated Akt activity is actually increased. |
| 4142 | 16880400 | This increased Akt activity correlates with increased phosphatidylinositol (3,4,5)-trisphosphate levels which are due, at least in part, to diminished activity of the (3,4,5)-trisphosphate phosphatase PTEN. |
| 4143 | 16880400 | Thus, the regulatory subunit p85alpha is a critical modulator of insulin sensitivity in vivo not only because of its effects on PI3K activation, but also as a regulator of PTEN activity. |
| 4144 | 16880400 | Phosphoinositide 3-kinase regulatory subunit p85alpha suppresses insulin action via positive regulation of PTEN. |
| 4145 | 16880400 | The phosphoinositide 3-kinase (PI3K) pathway is central to the metabolic actions of insulin on liver. |
| 4146 | 16880400 | Here, we show that mice with a liver-specific deletion of the p85alpha regulatory subunit of PI3K (L-Pik3r1KO) exhibit a paradoxical improvement of hepatic and peripheral insulin sensitivity. |
| 4147 | 16880400 | Although PI3K enzymatic activity is diminished in L-Pik3r1KO livers because of a reduced level of regulatory and catalytic subunits of PI3K, insulin-stimulated Akt activity is actually increased. |
| 4148 | 16880400 | This increased Akt activity correlates with increased phosphatidylinositol (3,4,5)-trisphosphate levels which are due, at least in part, to diminished activity of the (3,4,5)-trisphosphate phosphatase PTEN. |
| 4149 | 16880400 | Thus, the regulatory subunit p85alpha is a critical modulator of insulin sensitivity in vivo not only because of its effects on PI3K activation, but also as a regulator of PTEN activity. |
| 4150 | 16898568 | The mechanism through which FFA induces insulin resistance involves intramyocellular and intrahepatocellular accumulation of triglycerides and diacylglycerol, activation of several serine/threonine kinases, reduction in tyrosine phosphorylation of the insulin receptor substrate (IRS)-1/2, and impairment of the IRS/phosphatidylinositol 3-kinase pathway of insulin signaling. |
| 4151 | 16929141 | Leptin is primarily metabolized in the kidney, presumably by binding to megalin, a multiligand receptor in the proximal tubule, tubular uptake and endocytosis. |
| 4152 | 16929141 | In contrast, leptin did not influence TGF-beta1 production in mesangial cells, but the peptide stimulates glucose transport in these cells, increased collagen type I synthesis, and lead to an upregulation of surface TGF-beta type II receptors through signal transduction pathways involving phosphatidylinositol-3-kinase. |
| 4153 | 16929141 | In addition, transgenic mice with leptin overexpression demonstrated a increase in collagen type IV and fibronectin mRNA in the kidney. |
| 4154 | 16929378 | In the healthy state, insulin appears to have only minor effects on vascular function, because of the activation of opposing mediators such as nitric oxide and endothelin-1. |
| 4155 | 16929378 | Diabetes and obesity, however, are associated with selective insulin resistance in the phosphatidylinositol-3-kinase signaling pathway, which leads to reduced synthesis of nitric oxide, impaired metabolic control and compensatory hyperinsulinemia. |
| 4156 | 16929378 | By contrast, insulin signaling via extracellular signal-regulated kinase dependent pathways is relatively unaffected in diabetes, tipping the balance of insulin's actions so that they favor abnormal vasoreactivity, angiogenesis, and other pathways implicated in microvascular complications and hypertension. |
| 4157 | 16960657 | Chronic exposure to ketone bodies impairs glucose uptake in adult cardiomyocytes in response to insulin but not vanadate: the role of PI3-K. |
| 4158 | 16960657 | We have already shown that chronic exposure to the ketone body beta-hydroxybutyrate (OHB) decreases insulin-mediated activation of protein kinase B (PKB) and glucose uptake in cardiomyocytes. |
| 4159 | 16960657 | While chronic exposure to OHB did not alter insulin- or vanadate-mediated activation of the insulin receptor, it suppressed insulin receptor substrate-1 (IRS-1) tyrosine phosphorylation in response to both agonists. |
| 4160 | 16960657 | Furthermore, this treatment decreased by 54 and 36% the phosphorylation of the p85 regulatory subunit of phosphatidylinositol 3-kinase (PI3-K) and PKB in response to insulin, whereas it did not alter vanadate-mediated activation of these enzymes. |
| 4161 | 16960657 | Though OHB induced a 2.1-fold increase of basal ERK1/2 phosphorylation, inhibition of this enzyme with the MEK inhibitor PD98059 demonstrated that ERK1/2 did not participate in OHB-induced insulin resistance. |
| 4162 | 16960657 | In conclusion, ketone bodies promote insulin resistance probably through decreased activation of the PI3-K/PKB signaling cascade. |
| 4163 | 16960657 | Chronic exposure to ketone bodies impairs glucose uptake in adult cardiomyocytes in response to insulin but not vanadate: the role of PI3-K. |
| 4164 | 16960657 | We have already shown that chronic exposure to the ketone body beta-hydroxybutyrate (OHB) decreases insulin-mediated activation of protein kinase B (PKB) and glucose uptake in cardiomyocytes. |
| 4165 | 16960657 | While chronic exposure to OHB did not alter insulin- or vanadate-mediated activation of the insulin receptor, it suppressed insulin receptor substrate-1 (IRS-1) tyrosine phosphorylation in response to both agonists. |
| 4166 | 16960657 | Furthermore, this treatment decreased by 54 and 36% the phosphorylation of the p85 regulatory subunit of phosphatidylinositol 3-kinase (PI3-K) and PKB in response to insulin, whereas it did not alter vanadate-mediated activation of these enzymes. |
| 4167 | 16960657 | Though OHB induced a 2.1-fold increase of basal ERK1/2 phosphorylation, inhibition of this enzyme with the MEK inhibitor PD98059 demonstrated that ERK1/2 did not participate in OHB-induced insulin resistance. |
| 4168 | 16960657 | In conclusion, ketone bodies promote insulin resistance probably through decreased activation of the PI3-K/PKB signaling cascade. |
| 4169 | 16960657 | Chronic exposure to ketone bodies impairs glucose uptake in adult cardiomyocytes in response to insulin but not vanadate: the role of PI3-K. |
| 4170 | 16960657 | We have already shown that chronic exposure to the ketone body beta-hydroxybutyrate (OHB) decreases insulin-mediated activation of protein kinase B (PKB) and glucose uptake in cardiomyocytes. |
| 4171 | 16960657 | While chronic exposure to OHB did not alter insulin- or vanadate-mediated activation of the insulin receptor, it suppressed insulin receptor substrate-1 (IRS-1) tyrosine phosphorylation in response to both agonists. |
| 4172 | 16960657 | Furthermore, this treatment decreased by 54 and 36% the phosphorylation of the p85 regulatory subunit of phosphatidylinositol 3-kinase (PI3-K) and PKB in response to insulin, whereas it did not alter vanadate-mediated activation of these enzymes. |
| 4173 | 16960657 | Though OHB induced a 2.1-fold increase of basal ERK1/2 phosphorylation, inhibition of this enzyme with the MEK inhibitor PD98059 demonstrated that ERK1/2 did not participate in OHB-induced insulin resistance. |
| 4174 | 16960657 | In conclusion, ketone bodies promote insulin resistance probably through decreased activation of the PI3-K/PKB signaling cascade. |
| 4175 | 16973905 | APOE4-VLDL inhibits the HDL-activated phosphatidylinositol 3-kinase/Akt Pathway via the phosphoinositol phosphatase SHIP2. |
| 4176 | 16973905 | We show that APOE4-VLDL diminishes the phosphorylation of Akt by HDL but does not alter phosphorylation of c-Jun N-terminal kinase, p38, or Src family kinases by HDL. |
| 4177 | 16973905 | Furthermore APOE4-VLDL inhibits Akt phosphorylation by reducing the phosphatidylinositol 3-kinase product phosphatidylinositol-(3,4,5)-triphosphate (PI[3,4,5]P3). |
| 4178 | 16973905 | Therefore the activation of SHIP2 by APOE4-VLDL, with the subsequent inhibition of the HDL/Akt pathway, is a novel and significant biological mechanism and may be a critical intermediate by which APOE4 increases the risk of atherosclerotic CVD. |
| 4179 | 16973905 | APOE4-VLDL inhibits the HDL-activated phosphatidylinositol 3-kinase/Akt Pathway via the phosphoinositol phosphatase SHIP2. |
| 4180 | 16973905 | We show that APOE4-VLDL diminishes the phosphorylation of Akt by HDL but does not alter phosphorylation of c-Jun N-terminal kinase, p38, or Src family kinases by HDL. |
| 4181 | 16973905 | Furthermore APOE4-VLDL inhibits Akt phosphorylation by reducing the phosphatidylinositol 3-kinase product phosphatidylinositol-(3,4,5)-triphosphate (PI[3,4,5]P3). |
| 4182 | 16973905 | Therefore the activation of SHIP2 by APOE4-VLDL, with the subsequent inhibition of the HDL/Akt pathway, is a novel and significant biological mechanism and may be a critical intermediate by which APOE4 increases the risk of atherosclerotic CVD. |
| 4183 | 17003350 | The detection of mRNAs for insulin receptor (IR)A and IRB; insulin receptor substrate (IRS)-1 and IRS-2; phosphoinositide 3-kinase (PI3K) catalytic subunits p110alpha, p110beta, PI3KC2alpha, and PI3KC2gamma; phosphoinositide-dependent protein kinase-1; protein kinase B (PKB)alpha, PKBbeta, and PKBgamma in the beta-cell population suggests the presence of a functional insulin signaling cascade in human beta-cells. |
| 4184 | 17015939 | The CI extract increased the amount of glucose transporter isoforms 1 (GLUT1) and 4 (GLUT4) at the cell surface and enhanced expression of GLUT1 protein. |
| 4185 | 17015939 | Our findings suggest that GLUT1 protein synthesis and the activation of phosphatidylinositol 3-kinase (PI3K) are critical for the increase in glucose transporter activity at the plasma membrane and essential for the maximal induction of glucose transport by CI in L8 muscle cells. |
| 4186 | 17018841 | These high-glucose-induced changes in protein synthesis were phosphatidylinositol 3-kinase, Akt, and mammalian target of rapamycin (mTOR) dependent and transforming growth factor-beta independent. |
| 4187 | 17018841 | High glucose reduced AMPK alpha-subunit theronine (Thr) 172 phosphorylation, which required Akt activation. |
| 4188 | 17018841 | Metformin and 5-aminoimidazole-4-carboxamide-1beta-riboside (AICAR) increased AMPK phosphorylation, inhibited high-glucose stimulation of protein synthesis, and prevented high-glucose-induced changes in phosphorylation of 4E binding protein 1 and eukaryotic elongation factor 2. |
| 4189 | 17018841 | In diabetic rats, metformin and AICAR increased renal AMPK phosphorylation, reversed mTOR activation, and inhibited renal hypertrophy, without affecting hyperglycemia. |
| 4190 | 17046573 | Insulin and insulin-like growth factor-1 promote mast cell survival via activation of the phosphatidylinositol-3-kinase pathway. |
| 4191 | 17056071 | H-89 potentiates adipogenesis in 3T3-L1 cells by activating insulin signaling independently of protein kinase A. |
| 4192 | 17056071 | Among four kinds of protein kinase A (PKA) inhibitors tested, H-89 exhibited a unique action to remarkably enhance adipocyte differentiation of 3T3-L1 cells, whereas the other three PKA inhibitors, PKA inhibitor Fragment 14-22 (PKI), Rp-cAMP, and KT 5720, did not enhance adipocyte differentiation. |
| 4193 | 17056071 | H-89 also potentiated the phosphorylation of Akt and extracellular signal-regulated kinase (ERK) 1/2 in 3T3-L1 cells, which function as downstream signaling of insulin. |
| 4194 | 17056071 | Phosphoinositide 3-kinase (PI3K) inhibitor wortmannin and mitogen-activated protein kinase kinase (MEK) inhibitor PD 98059 suppressed both the H-89-induced promotion of adipocyte differentiation and the H-89-induced potentiation of phosphorylation of Akt and ERK1/2. |
| 4195 | 17056071 | Rho kinase inhibitor Y-27632 also promoted the phosphorylation of both Akt and ERK1/2 and enhanced adipocyte differentiation, although its effect was somewhat less than that of H-89. |
| 4196 | 17056071 | Even when cells were treated with a mixture of Y-27632 and H-89, the additive enhancing effects on both the insulin signaling and adipocyte differentiation were not detected. |
| 4197 | 17056071 | Therefore, it is suggested that the major possible mechanism whereby H-89 potentiates adipocyte differentiation of 3T3-L1 cells is activation of insulin signaling that is elicited mostly by inhibiting Rho/Rho kinase pathway. |
| 4198 | 17068137 | Developmental switch from prolonged insulin action to increased insulin sensitivity in protein tyrosine phosphatase 1B-deficient hepatocytes. |
| 4199 | 17068137 | Protein tyrosine phosphatase 1B (PTP1B) is a negative regulator of insulin signaling and a therapeutic target for type 2 diabetes. |
| 4200 | 17068137 | The purpose of this study was to evaluate the differences in insulin sensitivity between neonate and adult hepatocytes lacking PTP1B. |
| 4201 | 17068137 | PTP1B deficiency in immortalized neonatal hepatocytes prolonged insulin-induced tyrosine phosphorylation of the insulin receptor (IR) and IR substrates (IRS) -1, -2 compared with wild-type control cells. |
| 4202 | 17068137 | Endogenous IR and IRS-2 were down-regulated, whereas IRS-1 was up-regulated in PTP1B(-/-) neonatal hepatocytes and livers of PTP1B(-/-) neonates. |
| 4203 | 17068137 | Insulin-induced activation of phosphatidylinositol 3-kinase/Akt pathway was prolonged in PTP1B(-/-) immortalized neonatal hepatocytes. |
| 4204 | 17068137 | Rescue of PTP1B in deficient cells suppressed the prolonged insulin signaling, whereas RNA interference in wild-type cells promoted prolonged signaling. |
| 4205 | 17068137 | In primary neonatal PTP1B(-/-) hepatocytes, insulin prolonged the inhibition of gluconeogenic mRNAs, but the sensitivity to this inhibition was similar to wild-type cells. |
| 4206 | 17068137 | By contrast, in adult PTP1B-deficient livers, p85alpha was down-regulated compared with the wild type. |
| 4207 | 17068137 | Moreover, primary hepatocytes from adult PTP1B(-/-) mice displayed enhanced Akt phosphorylation and a more pronounced inhibition of gluconeogenic mRNAs than wild-type cells. |
| 4208 | 17068137 | Hepatic insulin sensitivity due to PTP1B deficiency is acquired through postnatal development. |
| 4209 | 17068137 | Thus, changes in IR and IRS-2 expression and in the balance between regulatory and catalytic subunits of phosphatidylinositol 3-kinase are necessary to achieve insulin sensitization in adult PTP1B(-/-) hepatocytes. |
| 4210 | 17068137 | Developmental switch from prolonged insulin action to increased insulin sensitivity in protein tyrosine phosphatase 1B-deficient hepatocytes. |
| 4211 | 17068137 | Protein tyrosine phosphatase 1B (PTP1B) is a negative regulator of insulin signaling and a therapeutic target for type 2 diabetes. |
| 4212 | 17068137 | The purpose of this study was to evaluate the differences in insulin sensitivity between neonate and adult hepatocytes lacking PTP1B. |
| 4213 | 17068137 | PTP1B deficiency in immortalized neonatal hepatocytes prolonged insulin-induced tyrosine phosphorylation of the insulin receptor (IR) and IR substrates (IRS) -1, -2 compared with wild-type control cells. |
| 4214 | 17068137 | Endogenous IR and IRS-2 were down-regulated, whereas IRS-1 was up-regulated in PTP1B(-/-) neonatal hepatocytes and livers of PTP1B(-/-) neonates. |
| 4215 | 17068137 | Insulin-induced activation of phosphatidylinositol 3-kinase/Akt pathway was prolonged in PTP1B(-/-) immortalized neonatal hepatocytes. |
| 4216 | 17068137 | Rescue of PTP1B in deficient cells suppressed the prolonged insulin signaling, whereas RNA interference in wild-type cells promoted prolonged signaling. |
| 4217 | 17068137 | In primary neonatal PTP1B(-/-) hepatocytes, insulin prolonged the inhibition of gluconeogenic mRNAs, but the sensitivity to this inhibition was similar to wild-type cells. |
| 4218 | 17068137 | By contrast, in adult PTP1B-deficient livers, p85alpha was down-regulated compared with the wild type. |
| 4219 | 17068137 | Moreover, primary hepatocytes from adult PTP1B(-/-) mice displayed enhanced Akt phosphorylation and a more pronounced inhibition of gluconeogenic mRNAs than wild-type cells. |
| 4220 | 17068137 | Hepatic insulin sensitivity due to PTP1B deficiency is acquired through postnatal development. |
| 4221 | 17068137 | Thus, changes in IR and IRS-2 expression and in the balance between regulatory and catalytic subunits of phosphatidylinositol 3-kinase are necessary to achieve insulin sensitization in adult PTP1B(-/-) hepatocytes. |
| 4222 | 17068290 | C-Peptide induces vascular smooth muscle cell proliferation: involvement of SRC-kinase, phosphatidylinositol 3-kinase, and extracellular signal-regulated kinase 1/2. |
| 4223 | 17082237 | Role of the Akt/FoxO3a pathway in TGF-beta1-mediated mesangial cell dysfunction: a novel mechanism related to diabetic kidney disease. |
| 4224 | 17082237 | TGF-beta is increased in MC under diabetic conditions and in DN and activates key signaling pathways, including the phosphoinositide-3-kinase/Akt (PI3K/Akt) pathway. |
| 4225 | 17082237 | We tested whether phosphorylation-mediated inactivation of FoxO3a by TGF-beta can mediate MC survival and oxidative stress. |
| 4226 | 17082237 | This FoxO3a inactivation was accompanied by significant decreases in the expression of two key FoxO3a target genes, the proapoptotic Bim and antioxidant manganese superoxide dismutase in MC. |
| 4227 | 17082237 | TGF-beta treatment triggered the nuclear exclusion of FoxO3a, significantly inhibited FoxO3a transcriptional activity, and markedly protected MC from apoptosis. |
| 4228 | 17082237 | A PI3K inhibitor blocked these TGF-beta effects. |
| 4229 | 17082237 | In summary, TGF-beta and diabetes can increase FoxO3a phosphorylation and transcriptional inactivation via PI3K/Akt. |
| 4230 | 17082237 | These new results suggest that Akt/FoxO pathway regulation may be a novel mechanism by which TGF-beta can induce unopposed MC survival and oxidant stress in early DN, thereby accelerating renal disease. |
| 4231 | 17082237 | Role of the Akt/FoxO3a pathway in TGF-beta1-mediated mesangial cell dysfunction: a novel mechanism related to diabetic kidney disease. |
| 4232 | 17082237 | TGF-beta is increased in MC under diabetic conditions and in DN and activates key signaling pathways, including the phosphoinositide-3-kinase/Akt (PI3K/Akt) pathway. |
| 4233 | 17082237 | We tested whether phosphorylation-mediated inactivation of FoxO3a by TGF-beta can mediate MC survival and oxidative stress. |
| 4234 | 17082237 | This FoxO3a inactivation was accompanied by significant decreases in the expression of two key FoxO3a target genes, the proapoptotic Bim and antioxidant manganese superoxide dismutase in MC. |
| 4235 | 17082237 | TGF-beta treatment triggered the nuclear exclusion of FoxO3a, significantly inhibited FoxO3a transcriptional activity, and markedly protected MC from apoptosis. |
| 4236 | 17082237 | A PI3K inhibitor blocked these TGF-beta effects. |
| 4237 | 17082237 | In summary, TGF-beta and diabetes can increase FoxO3a phosphorylation and transcriptional inactivation via PI3K/Akt. |
| 4238 | 17082237 | These new results suggest that Akt/FoxO pathway regulation may be a novel mechanism by which TGF-beta can induce unopposed MC survival and oxidant stress in early DN, thereby accelerating renal disease. |
| 4239 | 17082237 | Role of the Akt/FoxO3a pathway in TGF-beta1-mediated mesangial cell dysfunction: a novel mechanism related to diabetic kidney disease. |
| 4240 | 17082237 | TGF-beta is increased in MC under diabetic conditions and in DN and activates key signaling pathways, including the phosphoinositide-3-kinase/Akt (PI3K/Akt) pathway. |
| 4241 | 17082237 | We tested whether phosphorylation-mediated inactivation of FoxO3a by TGF-beta can mediate MC survival and oxidative stress. |
| 4242 | 17082237 | This FoxO3a inactivation was accompanied by significant decreases in the expression of two key FoxO3a target genes, the proapoptotic Bim and antioxidant manganese superoxide dismutase in MC. |
| 4243 | 17082237 | TGF-beta treatment triggered the nuclear exclusion of FoxO3a, significantly inhibited FoxO3a transcriptional activity, and markedly protected MC from apoptosis. |
| 4244 | 17082237 | A PI3K inhibitor blocked these TGF-beta effects. |
| 4245 | 17082237 | In summary, TGF-beta and diabetes can increase FoxO3a phosphorylation and transcriptional inactivation via PI3K/Akt. |
| 4246 | 17082237 | These new results suggest that Akt/FoxO pathway regulation may be a novel mechanism by which TGF-beta can induce unopposed MC survival and oxidant stress in early DN, thereby accelerating renal disease. |
| 4247 | 17085442 | Feeding and insulin increase leptin translation. |
| 4248 | 17085442 | The post-transcriptional mechanisms by which feeding and insulin increase leptin production are poorly understood. |
| 4249 | 17085442 | In vitro insulin treatment of adipose tissue from fed or starved rats for 2 h increased relative rates of leptin biosynthesis by 2-3-fold, and the effect was blocked by inhibition of phosphatidylinositol 3-kinase or mammalian target of rapamycin. |
| 4250 | 17085442 | Consistent with the hypothesis that feeding/insulin increases leptin translation, more leptin mRNA was associated with polysomes in adipose tissue of fed than starved rats, and in vitro incubation of adipose tissue of starved rats with insulin shifted leptin mRNA into polysomes. |
| 4251 | 17085442 | Insulin stimulated the expression of constructs that included both the full-length 5'-UTR and the inhibitory 3'-UTR, and the effect was blocked by inhibition of phosphatidylinositol 3-kinase or mammalian target of rapamycin. |
| 4252 | 17085442 | Our data suggest that insulin derepresses leptin translation by a mechanism that requires both the 5'-UTR and the 3'-UTR and may contribute to the increase in leptin production with feeding. |
| 4253 | 17085442 | Feeding and insulin increase leptin translation. |
| 4254 | 17085442 | The post-transcriptional mechanisms by which feeding and insulin increase leptin production are poorly understood. |
| 4255 | 17085442 | In vitro insulin treatment of adipose tissue from fed or starved rats for 2 h increased relative rates of leptin biosynthesis by 2-3-fold, and the effect was blocked by inhibition of phosphatidylinositol 3-kinase or mammalian target of rapamycin. |
| 4256 | 17085442 | Consistent with the hypothesis that feeding/insulin increases leptin translation, more leptin mRNA was associated with polysomes in adipose tissue of fed than starved rats, and in vitro incubation of adipose tissue of starved rats with insulin shifted leptin mRNA into polysomes. |
| 4257 | 17085442 | Insulin stimulated the expression of constructs that included both the full-length 5'-UTR and the inhibitory 3'-UTR, and the effect was blocked by inhibition of phosphatidylinositol 3-kinase or mammalian target of rapamycin. |
| 4258 | 17085442 | Our data suggest that insulin derepresses leptin translation by a mechanism that requires both the 5'-UTR and the 3'-UTR and may contribute to the increase in leptin production with feeding. |
| 4259 | 17088412 | Insulin regulation of gene expression and concentrations of white adipose tissue-derived proteins in vivo in healthy men: relation to adiponutrin. |
| 4260 | 17088412 | Adiponutrin is a newly described white adipose tissue (WAT)-derived protein whose function and regulation remain widely unclear in humans though it is suggested to be related to insulin sensitivity. |
| 4261 | 17088412 | Recently, we found that adiponutrin expression is reduced in type 2 diabetic subjects in basal and insulin-stimulated states. |
| 4262 | 17088412 | To examine adiponutrin regulation by the insulin pathway in relation to other WAT-related proteins with well-known relation to insulin signaling and action, we examined in healthy young men (1) the association of adiponutrin with p85alpha PI3K and HKII, leptin, adiponectin, and acylation-stimulating protein (ASP) and (2) the regulation of adiponutrin and WAT-derived proteins by 3-h hyperinsulinemic euglycemic clamp (HIEG). |
| 4263 | 17088412 | At baseline (N = 20), adiponutrin expressions were positively correlated with those of p85alpha PI3K (R = 0.54, P = 0.017), HKII (R = 0.58, P = 0.010), and serum leptin (R = 0.51, P = 0.036), but not with any other parameter measured including insulin sensitivity. |
| 4264 | 17088412 | Hyperinsulinemia (N = 10, +2365% above baseline) significantly increased the expression of adiponutrin (+770%, P = 0.002), p85alpha PI3K (+150%, P = 0.033), HKII (+147%, P = 0.007), and serum leptin (+11%, P = 0.031), while it decreased serum adiponectin (-15%, P = 0.001). |
| 4265 | 17088412 | In the insulin-stimulated state, adiponutrin mRNA expression levels correlated with basal p85alpha PI3K (R = 0.76, P = 0.018) and HKII (R = 0.86, P = 0.003) expression levels, with percentage increase in insulin (R = 0.73, P = 0.040), and with insulin-stimulated state HKII (R = 0.82, P = 0.007), leptin (R = 0.84, P = 0.005), and adiponectin (R = 0.85, P = 0.004) mRNA levels. |
| 4266 | 17088412 | In healthy young men, adiponutrin expression is upregulated [corrected] by hyperinsulinemia and is related to basal and/or insulin-stimulated p85alpha PI3K, HKII, adiponectin, and leptin expression levels. |
| 4267 | 17088412 | We hypothesize that insulin-mediated regulation of adiponutrin expression is under the PI3K pathway. |
| 4268 | 17088412 | Insulin regulation of gene expression and concentrations of white adipose tissue-derived proteins in vivo in healthy men: relation to adiponutrin. |
| 4269 | 17088412 | Adiponutrin is a newly described white adipose tissue (WAT)-derived protein whose function and regulation remain widely unclear in humans though it is suggested to be related to insulin sensitivity. |
| 4270 | 17088412 | Recently, we found that adiponutrin expression is reduced in type 2 diabetic subjects in basal and insulin-stimulated states. |
| 4271 | 17088412 | To examine adiponutrin regulation by the insulin pathway in relation to other WAT-related proteins with well-known relation to insulin signaling and action, we examined in healthy young men (1) the association of adiponutrin with p85alpha PI3K and HKII, leptin, adiponectin, and acylation-stimulating protein (ASP) and (2) the regulation of adiponutrin and WAT-derived proteins by 3-h hyperinsulinemic euglycemic clamp (HIEG). |
| 4272 | 17088412 | At baseline (N = 20), adiponutrin expressions were positively correlated with those of p85alpha PI3K (R = 0.54, P = 0.017), HKII (R = 0.58, P = 0.010), and serum leptin (R = 0.51, P = 0.036), but not with any other parameter measured including insulin sensitivity. |
| 4273 | 17088412 | Hyperinsulinemia (N = 10, +2365% above baseline) significantly increased the expression of adiponutrin (+770%, P = 0.002), p85alpha PI3K (+150%, P = 0.033), HKII (+147%, P = 0.007), and serum leptin (+11%, P = 0.031), while it decreased serum adiponectin (-15%, P = 0.001). |
| 4274 | 17088412 | In the insulin-stimulated state, adiponutrin mRNA expression levels correlated with basal p85alpha PI3K (R = 0.76, P = 0.018) and HKII (R = 0.86, P = 0.003) expression levels, with percentage increase in insulin (R = 0.73, P = 0.040), and with insulin-stimulated state HKII (R = 0.82, P = 0.007), leptin (R = 0.84, P = 0.005), and adiponectin (R = 0.85, P = 0.004) mRNA levels. |
| 4275 | 17088412 | In healthy young men, adiponutrin expression is upregulated [corrected] by hyperinsulinemia and is related to basal and/or insulin-stimulated p85alpha PI3K, HKII, adiponectin, and leptin expression levels. |
| 4276 | 17088412 | We hypothesize that insulin-mediated regulation of adiponutrin expression is under the PI3K pathway. |
| 4277 | 17088412 | Insulin regulation of gene expression and concentrations of white adipose tissue-derived proteins in vivo in healthy men: relation to adiponutrin. |
| 4278 | 17088412 | Adiponutrin is a newly described white adipose tissue (WAT)-derived protein whose function and regulation remain widely unclear in humans though it is suggested to be related to insulin sensitivity. |
| 4279 | 17088412 | Recently, we found that adiponutrin expression is reduced in type 2 diabetic subjects in basal and insulin-stimulated states. |
| 4280 | 17088412 | To examine adiponutrin regulation by the insulin pathway in relation to other WAT-related proteins with well-known relation to insulin signaling and action, we examined in healthy young men (1) the association of adiponutrin with p85alpha PI3K and HKII, leptin, adiponectin, and acylation-stimulating protein (ASP) and (2) the regulation of adiponutrin and WAT-derived proteins by 3-h hyperinsulinemic euglycemic clamp (HIEG). |
| 4281 | 17088412 | At baseline (N = 20), adiponutrin expressions were positively correlated with those of p85alpha PI3K (R = 0.54, P = 0.017), HKII (R = 0.58, P = 0.010), and serum leptin (R = 0.51, P = 0.036), but not with any other parameter measured including insulin sensitivity. |
| 4282 | 17088412 | Hyperinsulinemia (N = 10, +2365% above baseline) significantly increased the expression of adiponutrin (+770%, P = 0.002), p85alpha PI3K (+150%, P = 0.033), HKII (+147%, P = 0.007), and serum leptin (+11%, P = 0.031), while it decreased serum adiponectin (-15%, P = 0.001). |
| 4283 | 17088412 | In the insulin-stimulated state, adiponutrin mRNA expression levels correlated with basal p85alpha PI3K (R = 0.76, P = 0.018) and HKII (R = 0.86, P = 0.003) expression levels, with percentage increase in insulin (R = 0.73, P = 0.040), and with insulin-stimulated state HKII (R = 0.82, P = 0.007), leptin (R = 0.84, P = 0.005), and adiponectin (R = 0.85, P = 0.004) mRNA levels. |
| 4284 | 17088412 | In healthy young men, adiponutrin expression is upregulated [corrected] by hyperinsulinemia and is related to basal and/or insulin-stimulated p85alpha PI3K, HKII, adiponectin, and leptin expression levels. |
| 4285 | 17088412 | We hypothesize that insulin-mediated regulation of adiponutrin expression is under the PI3K pathway. |
| 4286 | 17088412 | Insulin regulation of gene expression and concentrations of white adipose tissue-derived proteins in vivo in healthy men: relation to adiponutrin. |
| 4287 | 17088412 | Adiponutrin is a newly described white adipose tissue (WAT)-derived protein whose function and regulation remain widely unclear in humans though it is suggested to be related to insulin sensitivity. |
| 4288 | 17088412 | Recently, we found that adiponutrin expression is reduced in type 2 diabetic subjects in basal and insulin-stimulated states. |
| 4289 | 17088412 | To examine adiponutrin regulation by the insulin pathway in relation to other WAT-related proteins with well-known relation to insulin signaling and action, we examined in healthy young men (1) the association of adiponutrin with p85alpha PI3K and HKII, leptin, adiponectin, and acylation-stimulating protein (ASP) and (2) the regulation of adiponutrin and WAT-derived proteins by 3-h hyperinsulinemic euglycemic clamp (HIEG). |
| 4290 | 17088412 | At baseline (N = 20), adiponutrin expressions were positively correlated with those of p85alpha PI3K (R = 0.54, P = 0.017), HKII (R = 0.58, P = 0.010), and serum leptin (R = 0.51, P = 0.036), but not with any other parameter measured including insulin sensitivity. |
| 4291 | 17088412 | Hyperinsulinemia (N = 10, +2365% above baseline) significantly increased the expression of adiponutrin (+770%, P = 0.002), p85alpha PI3K (+150%, P = 0.033), HKII (+147%, P = 0.007), and serum leptin (+11%, P = 0.031), while it decreased serum adiponectin (-15%, P = 0.001). |
| 4292 | 17088412 | In the insulin-stimulated state, adiponutrin mRNA expression levels correlated with basal p85alpha PI3K (R = 0.76, P = 0.018) and HKII (R = 0.86, P = 0.003) expression levels, with percentage increase in insulin (R = 0.73, P = 0.040), and with insulin-stimulated state HKII (R = 0.82, P = 0.007), leptin (R = 0.84, P = 0.005), and adiponectin (R = 0.85, P = 0.004) mRNA levels. |
| 4293 | 17088412 | In healthy young men, adiponutrin expression is upregulated [corrected] by hyperinsulinemia and is related to basal and/or insulin-stimulated p85alpha PI3K, HKII, adiponectin, and leptin expression levels. |
| 4294 | 17088412 | We hypothesize that insulin-mediated regulation of adiponutrin expression is under the PI3K pathway. |
| 4295 | 17088412 | Insulin regulation of gene expression and concentrations of white adipose tissue-derived proteins in vivo in healthy men: relation to adiponutrin. |
| 4296 | 17088412 | Adiponutrin is a newly described white adipose tissue (WAT)-derived protein whose function and regulation remain widely unclear in humans though it is suggested to be related to insulin sensitivity. |
| 4297 | 17088412 | Recently, we found that adiponutrin expression is reduced in type 2 diabetic subjects in basal and insulin-stimulated states. |
| 4298 | 17088412 | To examine adiponutrin regulation by the insulin pathway in relation to other WAT-related proteins with well-known relation to insulin signaling and action, we examined in healthy young men (1) the association of adiponutrin with p85alpha PI3K and HKII, leptin, adiponectin, and acylation-stimulating protein (ASP) and (2) the regulation of adiponutrin and WAT-derived proteins by 3-h hyperinsulinemic euglycemic clamp (HIEG). |
| 4299 | 17088412 | At baseline (N = 20), adiponutrin expressions were positively correlated with those of p85alpha PI3K (R = 0.54, P = 0.017), HKII (R = 0.58, P = 0.010), and serum leptin (R = 0.51, P = 0.036), but not with any other parameter measured including insulin sensitivity. |
| 4300 | 17088412 | Hyperinsulinemia (N = 10, +2365% above baseline) significantly increased the expression of adiponutrin (+770%, P = 0.002), p85alpha PI3K (+150%, P = 0.033), HKII (+147%, P = 0.007), and serum leptin (+11%, P = 0.031), while it decreased serum adiponectin (-15%, P = 0.001). |
| 4301 | 17088412 | In the insulin-stimulated state, adiponutrin mRNA expression levels correlated with basal p85alpha PI3K (R = 0.76, P = 0.018) and HKII (R = 0.86, P = 0.003) expression levels, with percentage increase in insulin (R = 0.73, P = 0.040), and with insulin-stimulated state HKII (R = 0.82, P = 0.007), leptin (R = 0.84, P = 0.005), and adiponectin (R = 0.85, P = 0.004) mRNA levels. |
| 4302 | 17088412 | In healthy young men, adiponutrin expression is upregulated [corrected] by hyperinsulinemia and is related to basal and/or insulin-stimulated p85alpha PI3K, HKII, adiponectin, and leptin expression levels. |
| 4303 | 17088412 | We hypothesize that insulin-mediated regulation of adiponutrin expression is under the PI3K pathway. |
| 4304 | 17088412 | Insulin regulation of gene expression and concentrations of white adipose tissue-derived proteins in vivo in healthy men: relation to adiponutrin. |
| 4305 | 17088412 | Adiponutrin is a newly described white adipose tissue (WAT)-derived protein whose function and regulation remain widely unclear in humans though it is suggested to be related to insulin sensitivity. |
| 4306 | 17088412 | Recently, we found that adiponutrin expression is reduced in type 2 diabetic subjects in basal and insulin-stimulated states. |
| 4307 | 17088412 | To examine adiponutrin regulation by the insulin pathway in relation to other WAT-related proteins with well-known relation to insulin signaling and action, we examined in healthy young men (1) the association of adiponutrin with p85alpha PI3K and HKII, leptin, adiponectin, and acylation-stimulating protein (ASP) and (2) the regulation of adiponutrin and WAT-derived proteins by 3-h hyperinsulinemic euglycemic clamp (HIEG). |
| 4308 | 17088412 | At baseline (N = 20), adiponutrin expressions were positively correlated with those of p85alpha PI3K (R = 0.54, P = 0.017), HKII (R = 0.58, P = 0.010), and serum leptin (R = 0.51, P = 0.036), but not with any other parameter measured including insulin sensitivity. |
| 4309 | 17088412 | Hyperinsulinemia (N = 10, +2365% above baseline) significantly increased the expression of adiponutrin (+770%, P = 0.002), p85alpha PI3K (+150%, P = 0.033), HKII (+147%, P = 0.007), and serum leptin (+11%, P = 0.031), while it decreased serum adiponectin (-15%, P = 0.001). |
| 4310 | 17088412 | In the insulin-stimulated state, adiponutrin mRNA expression levels correlated with basal p85alpha PI3K (R = 0.76, P = 0.018) and HKII (R = 0.86, P = 0.003) expression levels, with percentage increase in insulin (R = 0.73, P = 0.040), and with insulin-stimulated state HKII (R = 0.82, P = 0.007), leptin (R = 0.84, P = 0.005), and adiponectin (R = 0.85, P = 0.004) mRNA levels. |
| 4311 | 17088412 | In healthy young men, adiponutrin expression is upregulated [corrected] by hyperinsulinemia and is related to basal and/or insulin-stimulated p85alpha PI3K, HKII, adiponectin, and leptin expression levels. |
| 4312 | 17088412 | We hypothesize that insulin-mediated regulation of adiponutrin expression is under the PI3K pathway. |
| 4313 | 17097148 | Our laboratory has reported that insulin and growth factors regulate drug metabolizing enzyme gene and protein expression, including cytochromes P450 (CYP), glutathione S-transferases (GST) and microsomal epoxide hydrolase (mEH), through receptors which are members of the large receptor tyrosine kinase (RTK) family, and by downstream effectors such as phosphatidylinositol 3-kinase, mitogen activated protein kinase (MAPK), Akt/protein kinase B (PKB), mammalian target of rapamycin (mTOR), and the p70 ribosomal protein S6 kinase (p70S6 kinase). |
| 4314 | 17109620 | NRF2-dependent glutamate-L-cysteine ligase catalytic subunit expression mediates insulin protection against hyperglycemia- induced brain endothelial cell apoptosis. |
| 4315 | 17109620 | Insulin stimulated glutamate-L-cysteine ligase (GCL) activity by activation of phosphatidylinositol 3-kinase (PI3K)/Akt/mTOR signaling, increased serine phosphorylation and nuclear translocation of nuclear NF-E2-related factor 2 (Nrf2), and upregulation of Nrf2-dependent GCL-catalytic (GCLc) subunit expression. |
| 4316 | 17109620 | Expression of the GCL-modulatory subunit (GCLm) was unchanged. |
| 4317 | 17109620 | Inhibitors of insulin receptor tyrosine kinase, PI3K, Akt and mTOR abrogated insulin-induced Nrf2-mediated GCLc expression, redox balance, and IHEC survival. |
| 4318 | 17109620 | Activation of insulin signaling through PI3K/Akt/mTOR/Nrf2/ GCLc pathway affords significant cell protection by maintaining cellular redox balance. |
| 4319 | 17109620 | NRF2-dependent glutamate-L-cysteine ligase catalytic subunit expression mediates insulin protection against hyperglycemia- induced brain endothelial cell apoptosis. |
| 4320 | 17109620 | Insulin stimulated glutamate-L-cysteine ligase (GCL) activity by activation of phosphatidylinositol 3-kinase (PI3K)/Akt/mTOR signaling, increased serine phosphorylation and nuclear translocation of nuclear NF-E2-related factor 2 (Nrf2), and upregulation of Nrf2-dependent GCL-catalytic (GCLc) subunit expression. |
| 4321 | 17109620 | Expression of the GCL-modulatory subunit (GCLm) was unchanged. |
| 4322 | 17109620 | Inhibitors of insulin receptor tyrosine kinase, PI3K, Akt and mTOR abrogated insulin-induced Nrf2-mediated GCLc expression, redox balance, and IHEC survival. |
| 4323 | 17109620 | Activation of insulin signaling through PI3K/Akt/mTOR/Nrf2/ GCLc pathway affords significant cell protection by maintaining cellular redox balance. |
| 4324 | 17109620 | NRF2-dependent glutamate-L-cysteine ligase catalytic subunit expression mediates insulin protection against hyperglycemia- induced brain endothelial cell apoptosis. |
| 4325 | 17109620 | Insulin stimulated glutamate-L-cysteine ligase (GCL) activity by activation of phosphatidylinositol 3-kinase (PI3K)/Akt/mTOR signaling, increased serine phosphorylation and nuclear translocation of nuclear NF-E2-related factor 2 (Nrf2), and upregulation of Nrf2-dependent GCL-catalytic (GCLc) subunit expression. |
| 4326 | 17109620 | Expression of the GCL-modulatory subunit (GCLm) was unchanged. |
| 4327 | 17109620 | Inhibitors of insulin receptor tyrosine kinase, PI3K, Akt and mTOR abrogated insulin-induced Nrf2-mediated GCLc expression, redox balance, and IHEC survival. |
| 4328 | 17109620 | Activation of insulin signaling through PI3K/Akt/mTOR/Nrf2/ GCLc pathway affords significant cell protection by maintaining cellular redox balance. |
| 4329 | 17109853 | Inhibitory effect of 4-(2-aminoethyl)-benzenesulfonyl fluoride, a serine protease inhibitor, on PI3K inhibitor-induced CHOP expression. |
| 4330 | 17109853 | In the previous report, we found that phosphatidylinositol 3-kinase (PI3K) down-regulation is important for inducing CHOP expression, an endoplasmic reticulum stress-induced transcription factor. |
| 4331 | 17109853 | In the present study, we investigated the effect of 4-(2-aminoethyl)-benzenesulfonyl fluoride (AEBSF), a serine protease inhibitor, on PI3K inhibitor-induced CHOP expression. |
| 4332 | 17109853 | We found that AEBSF completely inhibited PI3K inhibitor-induced CHOP expression at both mRNA and protein levels. |
| 4333 | 17109853 | Inhibitory effect of 4-(2-aminoethyl)-benzenesulfonyl fluoride, a serine protease inhibitor, on PI3K inhibitor-induced CHOP expression. |
| 4334 | 17109853 | In the previous report, we found that phosphatidylinositol 3-kinase (PI3K) down-regulation is important for inducing CHOP expression, an endoplasmic reticulum stress-induced transcription factor. |
| 4335 | 17109853 | In the present study, we investigated the effect of 4-(2-aminoethyl)-benzenesulfonyl fluoride (AEBSF), a serine protease inhibitor, on PI3K inhibitor-induced CHOP expression. |
| 4336 | 17109853 | We found that AEBSF completely inhibited PI3K inhibitor-induced CHOP expression at both mRNA and protein levels. |
| 4337 | 17109853 | Inhibitory effect of 4-(2-aminoethyl)-benzenesulfonyl fluoride, a serine protease inhibitor, on PI3K inhibitor-induced CHOP expression. |
| 4338 | 17109853 | In the previous report, we found that phosphatidylinositol 3-kinase (PI3K) down-regulation is important for inducing CHOP expression, an endoplasmic reticulum stress-induced transcription factor. |
| 4339 | 17109853 | In the present study, we investigated the effect of 4-(2-aminoethyl)-benzenesulfonyl fluoride (AEBSF), a serine protease inhibitor, on PI3K inhibitor-induced CHOP expression. |
| 4340 | 17109853 | We found that AEBSF completely inhibited PI3K inhibitor-induced CHOP expression at both mRNA and protein levels. |
| 4341 | 17109853 | Inhibitory effect of 4-(2-aminoethyl)-benzenesulfonyl fluoride, a serine protease inhibitor, on PI3K inhibitor-induced CHOP expression. |
| 4342 | 17109853 | In the previous report, we found that phosphatidylinositol 3-kinase (PI3K) down-regulation is important for inducing CHOP expression, an endoplasmic reticulum stress-induced transcription factor. |
| 4343 | 17109853 | In the present study, we investigated the effect of 4-(2-aminoethyl)-benzenesulfonyl fluoride (AEBSF), a serine protease inhibitor, on PI3K inhibitor-induced CHOP expression. |
| 4344 | 17109853 | We found that AEBSF completely inhibited PI3K inhibitor-induced CHOP expression at both mRNA and protein levels. |
| 4345 | 17110421 | Because the atypical protein kinase C (PKC), PKCzeta, is involved in FA signaling in many cells, the role of PKCzeta in FA-induced GLP-1 secretion was investigated, using the murine GLUTag L cell line and primary rat intestinal L cells. |
| 4346 | 17110421 | Treatment with oleic acid (150-1000 microm) for 2 h increased GLP-1 secretion (P < 0.001), and this was abrogated by the PKCzeta inhibitor ZI (P < 0.05) and PKCzeta small interfering RNA transfection (P < 0.05) but not inhibition of classical/novel PKC isoforms. |
| 4347 | 17110421 | GLUTag cells expressed mRNA for the Gq-coupled FA receptor GPR120; however, oleic acid did not induce any changes in Akt, MAPK, or calcium, and pretreatment with LY294002 and PD98059 to inhibit phosphatidylinositol 3-kinase and MAPK, respectively, did not prevent the effects of oleic acid. |
| 4348 | 17110421 | These findings demonstrate that PKCzeta is required for oleic acid-induced GLP-1 secretion. |
| 4349 | 17119157 | PTEN regulation, a novel function for the p85 subunit of phosphoinositide 3-kinase. |
| 4350 | 17119157 | Class I(A) phosphatidylinositol 3-kinase (PI3K), which is composed of a p85 (regulatory) and p110 (catalytic) subunits, is the enzyme generating PI(3,4)P2 and PI(3,4,5)P3 following GFR stimulation. |
| 4351 | 17119157 | Examination of frequent genetic alterations in human cancer showed that PTEN (phosphatase with tensin homology on chromosome 10) is the major enzyme that decreases PI(3,4)P2 and PI(3,4,5)P3 cell content. |
| 4352 | 17119157 | The recent description of diminished PTEN activity in liver-conditional knockout mice lacking the p85alpha PI3K regulatory subunit reveals a previously unknown p85alpha-dependent negative-feedback pathway that controls PI(3,4)P2 and PI(3,4,5)P3 half-life by regulating PTEN. |
| 4353 | 17119157 | PTEN regulation, a novel function for the p85 subunit of phosphoinositide 3-kinase. |
| 4354 | 17119157 | Class I(A) phosphatidylinositol 3-kinase (PI3K), which is composed of a p85 (regulatory) and p110 (catalytic) subunits, is the enzyme generating PI(3,4)P2 and PI(3,4,5)P3 following GFR stimulation. |
| 4355 | 17119157 | Examination of frequent genetic alterations in human cancer showed that PTEN (phosphatase with tensin homology on chromosome 10) is the major enzyme that decreases PI(3,4)P2 and PI(3,4,5)P3 cell content. |
| 4356 | 17119157 | The recent description of diminished PTEN activity in liver-conditional knockout mice lacking the p85alpha PI3K regulatory subunit reveals a previously unknown p85alpha-dependent negative-feedback pathway that controls PI(3,4)P2 and PI(3,4,5)P3 half-life by regulating PTEN. |
| 4357 | 17130464 | Insulin-mediated phosphorylation of the proline-rich Akt substrate PRAS40 is impaired in insulin target tissues of high-fat diet-fed rats. |
| 4358 | 17130464 | Clinical insulin resistance is associated with decreased activation of phosphatidylinositol 3'-kinase (PI3K) and its downstream substrate protein kinase B (PKB)/Akt. |
| 4359 | 17130464 | In the present study, the effect of in vivo insulin action on phosphorylation of the PKB/Akt substrate 40 (PRAS40) was examined. |
| 4360 | 17130464 | In rat and mice, insulin stimulated PRAS40-Thr246 phosphorylation in skeletal and cardiac muscle, the liver, and adipose tissue in vivo. |
| 4361 | 17130464 | In cultured cell lines, insulin-mediated PRAS40 phosphorylation was prevented by the PI3K inhibitors wortmannin and LY294002. |
| 4362 | 17130464 | In conclusion, the current study identifies PRAS40 as a physiological target of in vivo insulin action. |
| 4363 | 17130464 | Phosphorylation of PRAS40 is increased by insulin in human, rat, and mouse insulin target tissues. |
| 4364 | 17130464 | Insulin-mediated phosphorylation of the proline-rich Akt substrate PRAS40 is impaired in insulin target tissues of high-fat diet-fed rats. |
| 4365 | 17130464 | Clinical insulin resistance is associated with decreased activation of phosphatidylinositol 3'-kinase (PI3K) and its downstream substrate protein kinase B (PKB)/Akt. |
| 4366 | 17130464 | In the present study, the effect of in vivo insulin action on phosphorylation of the PKB/Akt substrate 40 (PRAS40) was examined. |
| 4367 | 17130464 | In rat and mice, insulin stimulated PRAS40-Thr246 phosphorylation in skeletal and cardiac muscle, the liver, and adipose tissue in vivo. |
| 4368 | 17130464 | In cultured cell lines, insulin-mediated PRAS40 phosphorylation was prevented by the PI3K inhibitors wortmannin and LY294002. |
| 4369 | 17130464 | In conclusion, the current study identifies PRAS40 as a physiological target of in vivo insulin action. |
| 4370 | 17130464 | Phosphorylation of PRAS40 is increased by insulin in human, rat, and mouse insulin target tissues. |
| 4371 | 17130509 | Reciprocal relationships between endothelial dysfunction and insulin resistance may contribute to hypertension by causing imbalanced regulation of endothelial-derived vasodilators (e.g., nitric oxide) and vasoconstrictors (e.g., endothelin-1 [ET-1]). |
| 4372 | 17130509 | Treatment of SHRs with rosiglitazone (insulin sensitizer) and/or enalapril (ACE inhibitor) may simultaneously improve hypertension, insulin resistance, and endothelial dysfunction by rebalancing insulin-stimulated production of vasoactive mediators. |
| 4373 | 17130509 | When compared with WKY control rats, 12-week-old vehicle-treated SHRs were hypertensive, overweight, and insulin resistant, with elevated fasting levels of insulin and ET-1 and reduced serum adiponectin levels. |
| 4374 | 17130509 | Three-week treatment of SHRs with rosiglitazone and/or enalapril significantly reduced blood pressure, insulin resistance, fasting insulin, and ET-1 levels and increased adiponectin levels to values comparable with those observed in vehicle-treated WKY controls. |
| 4375 | 17130509 | By restoring phosphatidylinositol 3-kinase-dependent effects, rosiglitazone and/or enalapril therapy of SHRs also significantly improved vasodilator responses to insulin in MVB preconstricted with NE ex vivo. |
| 4376 | 17131467 | Hepatitis C virus (HCV) infection promotes insulin resistance, mainly by increased TNF production together with enhancement of suppressor of cytokine (SOC-3); both events block PI3K and Akt phosphorylation. |
| 4377 | 17131467 | The mechanisms by which insulin resistance promotes fibrosis progression include: (1) steatosis, (2) hyperleptinemia, (3) increased TNF production, (4) impaired expression of PPARgamma receptors. |
| 4378 | 17145138 | Bearing in mind that PI3K pathway, working synchronously with the diurnal rhythm of other metabolic hormones, is more active during daytime especially in postprandial period when aminoacids and glucose exist in the environment, and that decreased insulin response in PI3K pathway in diabetics, we may propose iatrogenically created hyperinsulinemia can cause more atherogenic effects via MAPK pathway. |
| 4379 | 17158030 | A novel method to monitor insulin-stimulated GTP-loading of Rab11a in cardiomyocytes. |
| 4380 | 17158030 | As a member of the Rab small GTPase family, Rab11a has been shown to be involved in different vesicle trafficking processes. |
| 4381 | 17158030 | In earlier work we identified Rab11a to be present in GLUT4-containing vesicles after insulin stimulation and showed its involvement in insulin-dependent glucose uptake. |
| 4382 | 17158030 | However, it remained elusive if Rab11a is directly activated by the insulin signalling cascade and at which step a potential activation occurs. |
| 4383 | 17158030 | To examine the GTP-loading of Rab11a, we introduced a biotinylated GTP-analog into H9c2-hIR cells, transiently overexpressing HA-tagged Rab11a, and measured its binding to the GTPase after insulin stimulation. |
| 4384 | 17158030 | We observed that Rab11a is transiently GTP-loaded after insulin stimulation with a 2.3 (+/-0.3) fold activation (n=5), reaching its maximum after 4 min and declining back to basal after additional 2 min. |
| 4385 | 17158030 | The activation of Rab11a is phosphatidylinositol 3-kinase (PI3-kinase) dependent and downstream of Akt, as shown by in vitro knockdown of this kinase. |
| 4386 | 17158030 | These data show that Rab11a is directly activated by insulin and represents an element of the GLUT4 trafficking machinery. |
| 4387 | 17161395 | Glucose stimulated MIN6 cell proliferation and this was inhibited by blockade of insulin secretion, by an anti-insulin antibody and by phosphatidylinositol-3 kinase (PI-3K) inhibition. |
| 4388 | 17161395 | These data indicate that insulin secreted by beta-cells in response to elevated glucose exerts autocrine effects to protect against apoptosis and stimulate proliferation, and suggest that the insulin signalling cascade, through the PI-3K pathway, may be an effective means of maintaining beta-cell mass in diabetes. |
| 4389 | 17161395 | Glucose stimulated MIN6 cell proliferation and this was inhibited by blockade of insulin secretion, by an anti-insulin antibody and by phosphatidylinositol-3 kinase (PI-3K) inhibition. |
| 4390 | 17161395 | These data indicate that insulin secreted by beta-cells in response to elevated glucose exerts autocrine effects to protect against apoptosis and stimulate proliferation, and suggest that the insulin signalling cascade, through the PI-3K pathway, may be an effective means of maintaining beta-cell mass in diabetes. |
| 4391 | 17183521 | Hyrtiosal, a PTP1B inhibitor from the marine sponge Hyrtios erectus, shows extensive cellular effects on PI3K/AKT activation, glucose transport, and TGFbeta/Smad2 signaling. |
| 4392 | 17183521 | Protein tyrosine phosphatase 1B (PTP1B) negatively regulates insulin signaling, and PTP1B inhibitors have been seen as promising therapeutic agents against obesity and type 2 diabetes. |
| 4393 | 17183521 | Here we report that the marine natural product hyrtiosal, from the marine sponge Hyrtios erectus, has been discovered to act as a PTP1B inhibitor and to show extensive cellular effects on PI3K/AKT activation, glucose transport, and TGFbeta/Smad2 signaling. |
| 4394 | 17183521 | Further study with an IN Cell Analyzer 1000 cellular fluorescence imaging instrument showed that hyrtiosal displayed potent activity in abolishing the retardation of AKT membrane translocation caused by PTP1B overexpression in CHO cells. |
| 4395 | 17183521 | Moreover, it was found that this newly identified PTP1B inhibitor could dramatically enhance the membrane translocation of the key glucose transporter Glut4 in PTP1B-overexpressed CHO cells. |
| 4396 | 17183521 | Additionally, in view of our recent finding that PTP1B was able to modulate insulin-mediated inhibition of Smad2 activation, hyrtiosal was also tested for its capabilities in the regulation of Smad2 activity through the PI3K/AKT pathway. |
| 4397 | 17183521 | The results showed that hyrtiosal could effectively facilitate insulin inhibition of Smad2 activation. |
| 4398 | 17183521 | Hyrtiosal, a PTP1B inhibitor from the marine sponge Hyrtios erectus, shows extensive cellular effects on PI3K/AKT activation, glucose transport, and TGFbeta/Smad2 signaling. |
| 4399 | 17183521 | Protein tyrosine phosphatase 1B (PTP1B) negatively regulates insulin signaling, and PTP1B inhibitors have been seen as promising therapeutic agents against obesity and type 2 diabetes. |
| 4400 | 17183521 | Here we report that the marine natural product hyrtiosal, from the marine sponge Hyrtios erectus, has been discovered to act as a PTP1B inhibitor and to show extensive cellular effects on PI3K/AKT activation, glucose transport, and TGFbeta/Smad2 signaling. |
| 4401 | 17183521 | Further study with an IN Cell Analyzer 1000 cellular fluorescence imaging instrument showed that hyrtiosal displayed potent activity in abolishing the retardation of AKT membrane translocation caused by PTP1B overexpression in CHO cells. |
| 4402 | 17183521 | Moreover, it was found that this newly identified PTP1B inhibitor could dramatically enhance the membrane translocation of the key glucose transporter Glut4 in PTP1B-overexpressed CHO cells. |
| 4403 | 17183521 | Additionally, in view of our recent finding that PTP1B was able to modulate insulin-mediated inhibition of Smad2 activation, hyrtiosal was also tested for its capabilities in the regulation of Smad2 activity through the PI3K/AKT pathway. |
| 4404 | 17183521 | The results showed that hyrtiosal could effectively facilitate insulin inhibition of Smad2 activation. |
| 4405 | 17183521 | Hyrtiosal, a PTP1B inhibitor from the marine sponge Hyrtios erectus, shows extensive cellular effects on PI3K/AKT activation, glucose transport, and TGFbeta/Smad2 signaling. |
| 4406 | 17183521 | Protein tyrosine phosphatase 1B (PTP1B) negatively regulates insulin signaling, and PTP1B inhibitors have been seen as promising therapeutic agents against obesity and type 2 diabetes. |
| 4407 | 17183521 | Here we report that the marine natural product hyrtiosal, from the marine sponge Hyrtios erectus, has been discovered to act as a PTP1B inhibitor and to show extensive cellular effects on PI3K/AKT activation, glucose transport, and TGFbeta/Smad2 signaling. |
| 4408 | 17183521 | Further study with an IN Cell Analyzer 1000 cellular fluorescence imaging instrument showed that hyrtiosal displayed potent activity in abolishing the retardation of AKT membrane translocation caused by PTP1B overexpression in CHO cells. |
| 4409 | 17183521 | Moreover, it was found that this newly identified PTP1B inhibitor could dramatically enhance the membrane translocation of the key glucose transporter Glut4 in PTP1B-overexpressed CHO cells. |
| 4410 | 17183521 | Additionally, in view of our recent finding that PTP1B was able to modulate insulin-mediated inhibition of Smad2 activation, hyrtiosal was also tested for its capabilities in the regulation of Smad2 activity through the PI3K/AKT pathway. |
| 4411 | 17183521 | The results showed that hyrtiosal could effectively facilitate insulin inhibition of Smad2 activation. |
| 4412 | 17198676 | Phosphodiesterase 3B (PDE3B), is known to play an important role in acute insulin and cAMP-mediated regulation of lipid metabolism, and PDE4 are the main PDE types expressed in adipocytes. |
| 4413 | 17198676 | Long-term treatment of 3T3-L1 adipocytes with insulin induced up-regulation of PDE3B and PDE4D in a phosphatidylinositol 3-kinase-dependent manner whereas long-term treatment with beta-adrenergic agonists induced down-regulation of PDE3B and up-regulation of PDE4D. |
| 4414 | 17198676 | Thus, PDE3B and PDE4D can be added to the list of genes regulated by insulin and cAMP-increasing hormones. |
| 4415 | 17198676 | Altered expression of PDE3B and PDE4D in response to long-term treatment with insulin and catecholamines may contribute to altered regulation of metabolism in diabetes. |
| 4416 | 17202326 | Augmented lipopolysaccharide-induced TNF-alpha production by peritoneal macrophages in type 2 diabetic mice is dependent on elevated glucose and requires p38 MAPK. |
| 4417 | 17202326 | In this study, we show that augmented LPS-induced TNF-alpha production by resident peritoneal macrophages (PerMphi) in type 2 diabetic (db/db) mice is dependent on elevated glucose and requires p38 MAPK. |
| 4418 | 17202326 | Examination of the TLR-4/MD2 complex and CD14 expression showed no difference between db/db and db/+ PerMphi. |
| 4419 | 17202326 | LPS-dependent stimulation of PI3K activity, ERK1/2 activation, and p38 kinase activity was greater in PerMphi from db/db mice as compared with db/+ mice. |
| 4420 | 17202326 | Only inhibition of p38 kinase blocked LPS-induced TNF-alpha production in PerMphi from db/db mice. |
| 4421 | 17202326 | Taken together, these data indicate that augmented TNF-alpha production induced by LPS in macrophages during diabetes is due to hyperglycemia and increased LPS-dependent activation of p38 kinase. |
| 4422 | 17208384 | Adipocyte-derived hormones, including adiponectin and leptin, regulate systemic insulin sensitivity in accordance to existing triglyceride reserves. |
| 4423 | 17208384 | Leptin levels reflect existing fat mass and the adipokine negatively regulates insulin action in adipose tissue. |
| 4424 | 17208384 | Adiponectin, on the other hand, preserves insulin sensitivity via transient increments of AMPK activity and its circulating levels seem to reflect the adipogenic capacity of adipose tissue. |
| 4425 | 17208384 | Because adiponectin and insulin synergize in their postprandial actions, it seems evident that inadequate adiponectin production causes systemic insulin resistance. |
| 4426 | 17208384 | As a consequence, compounds that either increase adiponectin production or mimic its actions can be considered as an efficient strategy for improving insulin sensitivity in type 2 diabetics. |
| 4427 | 17208384 | Finally, after delineating critical nodes of insulin and adipokine crosstalk, putative pathways are proposed by which adiponectin and leptin cooperatively regulate systemic insulin sensitivity in accordance to existing fat mass. |
| 4428 | 17208384 | By amplifying insulin action downstream of PI3K, leptin exerts negative feedback on insulin signaling via mTOR-dependent pathways that target IRS-1 for serine phosphorylation and protein degradation. |
| 4429 | 17208384 | Adiponectin-mediated increments of AMPK activity, on the other hand, may attenuate mTOR signaling, leading to the preservation of insulin sensitivity in periods of increased nutrient availability. |
| 4430 | 17208384 | Considering that leptin and adiponectin are inversely associated with BMI, the proposed model provides a plausible explanation for the observation that leptin exerts strong negative feedback on systemic insulin sensitivity, while increasing PIP3 availability. |
| 4431 | 17210752 | Bidirectional regulation of upstream IGF-I/insulin receptor signaling and downstream FOXO1 in cardiomyocytes. |
| 4432 | 17210752 | FOXO1 is a member of the forkhead transcriptional factor family, but how insulin and IGF-I receptor signaling regulate FOXO1 in cardiomyocytes is not well understood. |
| 4433 | 17210752 | This study was carried out to elucidate how IGF-I and insulin receptor signaling modulate FOXO1 in cardiomyocytes. |
| 4434 | 17210752 | In cardiomyocytes, activation of IGF-I receptor and insulin receptor lead to rapid phosphorylation of FOXO1. |
| 4435 | 17210752 | Inhibition of phosphatidylinositol 3-kinase/Akt pathway suppressed the effect of insulin and IGF-I on FOXO1 phosphorylation. |
| 4436 | 17210752 | To explore whether FOXO1 could modulate IGF-I and insulin signaling, a constitutively active FOXO1 was overexpressed in cardiomyocytes. |
| 4437 | 17210752 | The abundance of insulin receptor and IGF-I receptor was significantly upregulated in the cells overexpressing active FOXO1, accompanied by increased receptor phosphorylation upon insulin/IGF-I stimulation. |
| 4438 | 17210752 | Interestingly, overexpression of constitutively active FOXO1 also led to activation of MEK and Akt phosphorylation. |
| 4439 | 17210752 | IGF-I-stimulated MEK and Akt phosphorylation were augmented byoverexpression of constitutively active FOXO1. |
| 4440 | 17210752 | These findings indicate bidirectional regulation of insulin/IGF-I receptor signaling and FOXO1 in cardiomyocytes. |
| 4441 | 17210752 | FOXO1 may provide feedback control through upregulation of insulin and IGF-I receptor signaling. |
| 4442 | 17213573 | Angiotensin II and insulin crosstalk in the cardiovascular system. |
| 4443 | 17213573 | Under normal physiology, insulin exerts vasodilatory and pro-survival actions via the phosphatidylinositol 3-kinase (PI3-kinase) pathway and vasoconstrictive and mitogenic actions via the mitogen-activated protein kinase (MAPK) pathway in the vasculature. |
| 4444 | 17213573 | In the insulin resistant states, insulin signals through the PI3-kinase pathway are blunted but its signals through the MAPK cascade remain intact. |
| 4445 | 17213573 | Angiotensin II impairs insulin signaling, induces inflammation via the NF-kappaB pathway, reduces nitric oxide availability and facilitates vasoconstriction, leading to insulin resistance and endothelial dysfunction. |
| 4446 | 17218436 | We gave insulin intravenously to these rats and determined the association of glucose transporter-4 with plasma membranes, as well as the phosphorylation of phosphoinositide-dependent protein kinase-1 (PDK1), Akt, and PKCzeta. |
| 4447 | 17218436 | After insulin treatment, EtOH-exposed rats had decreased membrane glucose transporter-4, PDK1, Akt, and PKCzeta in the gastrocnemius muscle, compared with control rats. |
| 4448 | 17218436 | Insulin stimulation of PDK1, Akt, and PKCzeta phosphorylation was also reduced. |
| 4449 | 17218436 | In addition, the expression of the protein tribbles-3 and the phosphatase enzyme activity of phosphatase and tensin homolog deleted on chromosome 10 (PTEN), which prevent Akt activation, were increased in muscle from EtOH-exposed rats. |
| 4450 | 17218436 | Female rat offspring exposed to EtOH in utero develop insulin-resistant diabetes in association with excessive PTEN and tribbles-3 signaling downstream of the phosphatidylinositol 3-kinase pathway in skeletal muscle, which may be a mechanism for the abnormal glucose tolerance. |
| 4451 | 17242177 | Simultaneous administration of HGF and FFAs significantly suppressed the impaired insulin secretion and FFA-induced apoptosis. |
| 4452 | 17242177 | These effects appear to be mediated by bcl-2 and phosphatidylinositol 3 kinase (PI3K)/Akt pathways. |
| 4453 | 17242177 | Indeed, HGF increased mRNA and protein expression of bcl-2 downregulated by FFAs-treatment; moreover, pre-treatment with the specific PI3-kinase inhibitor LY294002, significantly abolished the protective effect of HGF. |
| 4454 | 17242177 | In conclusion, in rat insulin-producing RINm5F cells, HGF exerts its prosurvival effect by counteracting the increased intracellular oxidative stress and, consequently, by inhibiting apoptosis induced by chronic exposure to FFAs. |
| 4455 | 17242212 | Interleukin-6 impairs the insulin signaling pathway, promoting production of nitric oxide in human umbilical vein endothelial cells. |
| 4456 | 17242212 | Interleukin 6 (IL-6) is an independent predictor of type 2 diabetes and cardiovascular disease and is correlated with insulin resistance. |
| 4457 | 17242212 | Insulin stimulates nitric oxide (NO) production through the IRS-1/PI3-kinase/Akt/eNOS pathway (where IRS-1 is insulin receptor substrate 1, PI3-kinase is phosphatidylinositol 3-kinase, and eNOS is endothelial NO synthase). |
| 4458 | 17242212 | We asked if IL-6 affects insulin vasodilator action both in human umbilical vein endothelial cells (HUVEC) and in the aortas of C57BL/6J mice and whether this inhibitory effect was caused by increased Ser phosphorylation of IRS-1. |
| 4459 | 17242212 | We observed that IL-6 increased IRS-1 phosphorylation at Ser(312) and Ser(616); these effects were paralleled by increased Jun N-terminal protein kinase (JNK) and extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation and reversed by JNK and ERK1/2 inhibition. |
| 4460 | 17242212 | In addition, IL-6 treatment resulted in impaired IRS-1 phosphorylation at Tyr(612), a site essential for engaging PI3-kinase. |
| 4461 | 17242212 | Furthermore, IL-6 treatment reduced insulin-stimulated phosphorylation of eNOS at the stimulatory Ser(1177) site and impaired insulin-stimulated eNOS dephosphorylation at the inhibitory Thr(495) site. |
| 4462 | 17242212 | Insulin-stimulated eNOS activation and NO production were also inhibited by IL-6; these effects were reversed by inhibition of JNK and ERK1/2. |
| 4463 | 17242212 | Treatment of C57BL/6J mice with IL-6 resulted in impaired insulin-dependent activation of the Akt/eNOS pathway in the aorta as a result of JNK and ERK1/2 activation. |
| 4464 | 17242212 | Our data suggest that IL-6 impairs the vasodilator effects of insulin that are mediated by the IRS-1/PI3-kinase/Akt/eNOS pathway through activation of JNK and ERK1/2. |
| 4465 | 17255529 | Axl/phosphatidylinositol 3-kinase signaling inhibits mineral deposition by vascular smooth muscle cells. |
| 4466 | 17255529 | This study tests the hypothesis that Axl prevents the deposition of a calcified matrix by vascular smooth muscle cells (VSMCs) and that this occurs via the phosphatidylinositol 3-kinase (PI3K) signaling pathway. |
| 4467 | 17255529 | Second, we demonstrate that overexpression of wild-type Axl, using recombinant adenoviruses, enhances Axl phosphorylation and downstream signaling via PI3K and Akt. |
| 4468 | 17255529 | Third, the addition of a PI3K inhibitor, wortmannin, negates the inhibition of mineralization by overexpression of wild-type Axl, suggesting that activation of downstream signaling via PI3K is crucial for its inhibitory activity. |
| 4469 | 17255529 | Axl/phosphatidylinositol 3-kinase signaling inhibits mineral deposition by vascular smooth muscle cells. |
| 4470 | 17255529 | This study tests the hypothesis that Axl prevents the deposition of a calcified matrix by vascular smooth muscle cells (VSMCs) and that this occurs via the phosphatidylinositol 3-kinase (PI3K) signaling pathway. |
| 4471 | 17255529 | Second, we demonstrate that overexpression of wild-type Axl, using recombinant adenoviruses, enhances Axl phosphorylation and downstream signaling via PI3K and Akt. |
| 4472 | 17255529 | Third, the addition of a PI3K inhibitor, wortmannin, negates the inhibition of mineralization by overexpression of wild-type Axl, suggesting that activation of downstream signaling via PI3K is crucial for its inhibitory activity. |
| 4473 | 17255529 | Axl/phosphatidylinositol 3-kinase signaling inhibits mineral deposition by vascular smooth muscle cells. |
| 4474 | 17255529 | This study tests the hypothesis that Axl prevents the deposition of a calcified matrix by vascular smooth muscle cells (VSMCs) and that this occurs via the phosphatidylinositol 3-kinase (PI3K) signaling pathway. |
| 4475 | 17255529 | Second, we demonstrate that overexpression of wild-type Axl, using recombinant adenoviruses, enhances Axl phosphorylation and downstream signaling via PI3K and Akt. |
| 4476 | 17255529 | Third, the addition of a PI3K inhibitor, wortmannin, negates the inhibition of mineralization by overexpression of wild-type Axl, suggesting that activation of downstream signaling via PI3K is crucial for its inhibitory activity. |
| 4477 | 17255529 | Axl/phosphatidylinositol 3-kinase signaling inhibits mineral deposition by vascular smooth muscle cells. |
| 4478 | 17255529 | This study tests the hypothesis that Axl prevents the deposition of a calcified matrix by vascular smooth muscle cells (VSMCs) and that this occurs via the phosphatidylinositol 3-kinase (PI3K) signaling pathway. |
| 4479 | 17255529 | Second, we demonstrate that overexpression of wild-type Axl, using recombinant adenoviruses, enhances Axl phosphorylation and downstream signaling via PI3K and Akt. |
| 4480 | 17255529 | Third, the addition of a PI3K inhibitor, wortmannin, negates the inhibition of mineralization by overexpression of wild-type Axl, suggesting that activation of downstream signaling via PI3K is crucial for its inhibitory activity. |
| 4481 | 17259385 | Protein-tyrosine phosphatase 1B-deficient myocytes show increased insulin sensitivity and protection against tumor necrosis factor-alpha-induced insulin resistance. |
| 4482 | 17259385 | Protein-tyrosine phosphatase (PTP)1B is a negative regulator of insulin signaling and a therapeutic target for type 2 diabetes. |
| 4483 | 17259385 | In this study, we have assessed the role of PTP1B in the insulin sensitivity of skeletal muscle under physiological and insulin-resistant conditions. |
| 4484 | 17259385 | PTP1B(-/-) myocytes showed enhanced insulin-dependent activation of insulin receptor autophosphorylation and downstream signaling (tyrosine phosphorylation of insulin receptor substrate [IRS]-1 and IRS-2, activation of phosphatidylinositol 3-kinase, and serine phosphorylation of AKT), compared with wild-type cells. |
| 4485 | 17259385 | Accordingly, PTP1B(-/-) myocytes displayed higher insulin-dependent stimulation of glucose uptake and GLUT4 translocation to the plasma membrane than wild-type cells. |
| 4486 | 17259385 | Treatment with tumor necrosis factor-alpha (TNF-alpha) induced insulin resistance on glucose uptake, impaired insulin signaling, and increased PTP1B activity in wild-type cells. |
| 4487 | 17259385 | Conversely, the lack of PTP1B confers protection against insulin resistance by TNF-alpha in myocyte cell lines and in adult male mice. |
| 4488 | 17259385 | Wild-type mice treated with TNF-alpha developed a pronounced hyperglycemia along the glucose tolerance test, accompanied by an impaired insulin signaling and increased PTP1B activity in muscle. |
| 4489 | 17259385 | However, mice lacking PTP1B maintained a rapid clearance of glucose and insulin sensitivity and displayed normal muscle insulin signaling regardless the presence of TNF-alpha. |
| 4490 | 17259394 | High glucose, high insulin, and their combination rapidly induce laminin-beta1 synthesis by regulation of mRNA translation in renal epithelial cells. |
| 4491 | 17259394 | We investigated regulation of laminin-beta1 synthesis in murine renal proximal tubular epithelial cells by 30 mmol/l glucose (high glucose), 1 nmol/l insulin (high insulin), and their combination (high glucose+high insulin), simulating conditions observed during progression of type 2 diabetes. |
| 4492 | 17259394 | Compared with 5 mmol/l glucose and no insulin (control), high glucose alone, high insulin alone, or high glucose+high insulin together increased laminin-beta1 chain protein synthesis within 5 min, lasting for up to 60 min with no change in laminin-beta1 mRNA levels. |
| 4493 | 17259394 | High glucose, high insulin, and high glucose+high insulin stimulated phosphorylation of 4E-BP1, a repressor binding protein for eukaryotic initiation factor 4E (eIF4E), that was dependent on activation of phosphatidylinositol 3-kinase, Akt, and mammalian target of rapamycin. |
| 4494 | 17259394 | High glucose, high insulin, and high glucose+high insulin also promoted release of eIF4E from 4E-BP1, phosphorylation of eIF4E, and increase in eIF4E association with eIF4G, critical events in the initiation phase of mRNA translation. |
| 4495 | 17259394 | High glucose, high insulin, and high glucose+high insulin increased Erk phosphorylation, which is an upstream regulator of eIF4E phosphorylation, and PD098059, which is a MEK inhibitor that blocks Erk activation, abolished laminin-beta1 synthesis. |
| 4496 | 17259394 | This is the first demonstration of rapid increment in laminin-beta1 synthesis by regulation of its mRNA translation by cells exposed to high glucose, high insulin, or high glucose+high insulin. |
| 4497 | 17264162 | We now demonstrate that insulin-stimulated transcription of c-fos and glucokinase genes is activated simultaneously in the insulin-producing beta-cell via IR-B localized in different cellular compartments. |
| 4498 | 17264162 | Insulin activates the glucokinase gene from plasma membrane-standing IR-B, while c-fos gene activation is dependent on clathrin-mediated IR-B-endocytosis and signaling from early endosomes. |
| 4499 | 17264162 | Moreover, glucokinase gene up-regulation requires the integrity of the juxtamembrane IR-B NPEY-motif and signaling via PI3K-C2alpha-like/PDK1/PKB, while c-fos gene activation requires the intact C-terminal YTHM-motif and signaling via PI3K Ia/Shc/MEK1/ERK. |
| 4500 | 17266615 | Mechanisms underlying these alterations include differential expression of equilibrative nucleoside transporters (ENTs), cationic amino acid transporters (CATs), and NOS. |
| 4501 | 17266615 | Modulation of ENTs, CATs, and NOS expression and activity in endothelium involves protein kinase C (PKC), mitogen-activated protein kinases p42 and p44 (p42/44(mapk)), calcium, and phosphatidyl inositol 3 kinase (PI3k), among others. |
| 4502 | 17266615 | However, information regarding the transcriptional modulation of ENTs, CATs, and NOS is limited. |
| 4503 | 17266615 | This review focuses on the effect of transcriptional and post-transcriptional regulatory mechanisms involved in the modulation of ENTs and CATs, and NOS expression and activity, and the consequences for foetal endothelial function in GD, IUGR and PE. |
| 4504 | 17272402 | Tissue kallikrein reverses insulin resistance and attenuates nephropathy in diabetic rats by activation of phosphatidylinositol 3-kinase/protein kinase B and adenosine 5'-monophosphate-activated protein kinase signaling pathways. |
| 4505 | 17272402 | We previously reported that iv delivery of the human tissue kallikrein (HK) gene reduced blood pressure and plasma insulin levels in fructose-induced hypertensive rats with insulin resistance. |
| 4506 | 17272402 | The expression of phosphatidylinositol 3-kinase p110 catalytic subunit and the levels of phosphorylation at residue Thr-308 of Akt, insulin receptor B, and AMP-activated protein kinases were significantly decreased in organs from diabetic animals. |
| 4507 | 17272402 | Tissue kallikrein reverses insulin resistance and attenuates nephropathy in diabetic rats by activation of phosphatidylinositol 3-kinase/protein kinase B and adenosine 5'-monophosphate-activated protein kinase signaling pathways. |
| 4508 | 17272402 | We previously reported that iv delivery of the human tissue kallikrein (HK) gene reduced blood pressure and plasma insulin levels in fructose-induced hypertensive rats with insulin resistance. |
| 4509 | 17272402 | The expression of phosphatidylinositol 3-kinase p110 catalytic subunit and the levels of phosphorylation at residue Thr-308 of Akt, insulin receptor B, and AMP-activated protein kinases were significantly decreased in organs from diabetic animals. |
| 4510 | 17283057 | The p85alpha regulatory subunit of phosphoinositide 3-kinase potentiates c-Jun N-terminal kinase-mediated insulin resistance. |
| 4511 | 17283057 | While the molecular mechanisms of insulin resistance are multiple, recent evidence suggests that attenuation of insulin signaling by c-Jun N-terminal kinase (JNK) may be a central part of the pathobiology of insulin resistance. |
| 4512 | 17283057 | Here we demonstrate that the p85alpha regulatory subunit of phosphoinositide 3-kinase (PI3K), a key mediator of insulin's metabolic actions, is also required for the activation of JNK in states of insulin resistance, including high-fat diet-induced obesity and JNK1 overexpression. |
| 4513 | 17283057 | The requirement of the p85alpha regulatory subunit for JNK occurs independently of its role as a component of the PI3K heterodimer and occurs only in response to specific stimuli, namely, insulin and tunicamycin, a chemical that induces endoplasmic reticulum stress. |
| 4514 | 17283057 | We further show that insulin and p85 activate JNK by via cdc42 and MKK4. |
| 4515 | 17283057 | The activation of this cdc42/JNK pathway requires both an intact N terminus and functional SH2 domains within the C terminus of the p85alpha regulatory subunit. |
| 4516 | 17283057 | Thus, p85alpha plays a dual role in regulating insulin sensitivity and may mediate cross talk between the PI3K and stress kinase pathways. |
| 4517 | 17283057 | The p85alpha regulatory subunit of phosphoinositide 3-kinase potentiates c-Jun N-terminal kinase-mediated insulin resistance. |
| 4518 | 17283057 | While the molecular mechanisms of insulin resistance are multiple, recent evidence suggests that attenuation of insulin signaling by c-Jun N-terminal kinase (JNK) may be a central part of the pathobiology of insulin resistance. |
| 4519 | 17283057 | Here we demonstrate that the p85alpha regulatory subunit of phosphoinositide 3-kinase (PI3K), a key mediator of insulin's metabolic actions, is also required for the activation of JNK in states of insulin resistance, including high-fat diet-induced obesity and JNK1 overexpression. |
| 4520 | 17283057 | The requirement of the p85alpha regulatory subunit for JNK occurs independently of its role as a component of the PI3K heterodimer and occurs only in response to specific stimuli, namely, insulin and tunicamycin, a chemical that induces endoplasmic reticulum stress. |
| 4521 | 17283057 | We further show that insulin and p85 activate JNK by via cdc42 and MKK4. |
| 4522 | 17283057 | The activation of this cdc42/JNK pathway requires both an intact N terminus and functional SH2 domains within the C terminus of the p85alpha regulatory subunit. |
| 4523 | 17283057 | Thus, p85alpha plays a dual role in regulating insulin sensitivity and may mediate cross talk between the PI3K and stress kinase pathways. |
| 4524 | 17283057 | The p85alpha regulatory subunit of phosphoinositide 3-kinase potentiates c-Jun N-terminal kinase-mediated insulin resistance. |
| 4525 | 17283057 | While the molecular mechanisms of insulin resistance are multiple, recent evidence suggests that attenuation of insulin signaling by c-Jun N-terminal kinase (JNK) may be a central part of the pathobiology of insulin resistance. |
| 4526 | 17283057 | Here we demonstrate that the p85alpha regulatory subunit of phosphoinositide 3-kinase (PI3K), a key mediator of insulin's metabolic actions, is also required for the activation of JNK in states of insulin resistance, including high-fat diet-induced obesity and JNK1 overexpression. |
| 4527 | 17283057 | The requirement of the p85alpha regulatory subunit for JNK occurs independently of its role as a component of the PI3K heterodimer and occurs only in response to specific stimuli, namely, insulin and tunicamycin, a chemical that induces endoplasmic reticulum stress. |
| 4528 | 17283057 | We further show that insulin and p85 activate JNK by via cdc42 and MKK4. |
| 4529 | 17283057 | The activation of this cdc42/JNK pathway requires both an intact N terminus and functional SH2 domains within the C terminus of the p85alpha regulatory subunit. |
| 4530 | 17283057 | Thus, p85alpha plays a dual role in regulating insulin sensitivity and may mediate cross talk between the PI3K and stress kinase pathways. |
| 4531 | 17286556 | Regulation of adiponectin and leptin secretion and expression by insulin through a PI3K-PDE3B dependent mechanism in rat primary adipocytes. |
| 4532 | 17286556 | Adiponectin is intimately involved in the regulation of insulin sensitivity, carbohydrate and lipid metabolism, and cardiovascular functions. |
| 4533 | 17286556 | The opposing effects of isoprenaline and insulin could be explained by differential regulation of intracellular cAMP levels, since cAMP analogues suppressed adiponectin secretion and expression in a fashion similar to isoprenaline, and insulin blocked the inhibitory effects of the cAMP analogue hydrolysable by PDE (phosphodiesterase). |
| 4534 | 17286556 | A specific PDE3 inhibitor, milrinone, and PI3K (phosphoinositide 3-kinase) inhibitors abolished the effects of insulin on adiponectin secretion and expression. |
| 4535 | 17286556 | In the same studies, leptin secretion and expression displayed a similar pattern of regulation to adiponectin. |
| 4536 | 17286556 | We conclude that insulin and beta-agonists act directly at the adipocytes in opposing fashions to regulate the production of adiponectin and leptin, and that a PI3K-PDE3B-cAMP pathway mediates the effects of insulin to restore beta-agonist/cAMP-suppressed secretion and expression of these two adipokines. |
| 4537 | 17286556 | Regulation of adiponectin and leptin secretion and expression by insulin through a PI3K-PDE3B dependent mechanism in rat primary adipocytes. |
| 4538 | 17286556 | Adiponectin is intimately involved in the regulation of insulin sensitivity, carbohydrate and lipid metabolism, and cardiovascular functions. |
| 4539 | 17286556 | The opposing effects of isoprenaline and insulin could be explained by differential regulation of intracellular cAMP levels, since cAMP analogues suppressed adiponectin secretion and expression in a fashion similar to isoprenaline, and insulin blocked the inhibitory effects of the cAMP analogue hydrolysable by PDE (phosphodiesterase). |
| 4540 | 17286556 | A specific PDE3 inhibitor, milrinone, and PI3K (phosphoinositide 3-kinase) inhibitors abolished the effects of insulin on adiponectin secretion and expression. |
| 4541 | 17286556 | In the same studies, leptin secretion and expression displayed a similar pattern of regulation to adiponectin. |
| 4542 | 17286556 | We conclude that insulin and beta-agonists act directly at the adipocytes in opposing fashions to regulate the production of adiponectin and leptin, and that a PI3K-PDE3B-cAMP pathway mediates the effects of insulin to restore beta-agonist/cAMP-suppressed secretion and expression of these two adipokines. |
| 4543 | 17289286 | Insulin-like growth factor-1 (IGF-1) is a hormone and growth factor closely related to insulin. |
| 4544 | 17289286 | The autocrine/paracrine actions of IGF-1 involve activation of inducible nitric oxide synthase (iNOS) and the Na(+), K(+)-ATPase sodium pump in cardiovascular tissues. |
| 4545 | 17289286 | We hypothesize that impaired IGF-1-induced sodium pump activity/expression in rats with type 1 diabetes is related to activation of phosphatidylinositol 3 kinase (PI3K)/cytosolic phospholipase 2 (cPLA(2))/protein kinase B (Akt) signaling, and that IGF-1 prevents acute and chronic dysfunction of iNOS and sodium pump activity in a chemically induced model of type 1 diabetes, the streptozotocin-treated rat heart (STZ). |
| 4546 | 17289286 | Understanding how iNOS and sodium pump activity are regulated by IGF-1 activation of the PI3K/cPLA(2)/Akt cascade should provide novel and fundamental knowledge regarding the regulatory actions of IGF-1 in promoting vasodilation. |
| 4547 | 17289286 | Since insulin resistance is currently a major focus of research, the use of IGF-1 to improve insulin resistance and glucose metabolism has opened a new arena for treatment of comorbid conditions. |
| 4548 | 17289286 | Insulin-like growth factor-1 (IGF-1) is a hormone and growth factor closely related to insulin. |
| 4549 | 17289286 | The autocrine/paracrine actions of IGF-1 involve activation of inducible nitric oxide synthase (iNOS) and the Na(+), K(+)-ATPase sodium pump in cardiovascular tissues. |
| 4550 | 17289286 | We hypothesize that impaired IGF-1-induced sodium pump activity/expression in rats with type 1 diabetes is related to activation of phosphatidylinositol 3 kinase (PI3K)/cytosolic phospholipase 2 (cPLA(2))/protein kinase B (Akt) signaling, and that IGF-1 prevents acute and chronic dysfunction of iNOS and sodium pump activity in a chemically induced model of type 1 diabetes, the streptozotocin-treated rat heart (STZ). |
| 4551 | 17289286 | Understanding how iNOS and sodium pump activity are regulated by IGF-1 activation of the PI3K/cPLA(2)/Akt cascade should provide novel and fundamental knowledge regarding the regulatory actions of IGF-1 in promoting vasodilation. |
| 4552 | 17289286 | Since insulin resistance is currently a major focus of research, the use of IGF-1 to improve insulin resistance and glucose metabolism has opened a new arena for treatment of comorbid conditions. |
| 4553 | 17306383 | CCK causes PKD1 activation in pancreatic acini by signaling through PKC-delta and PKC-independent pathways. |
| 4554 | 17306383 | CCK activated PKD1 and caused a time- and dose-dependent increase in serine phosphorylation by activation of high- and low-affinity CCK(A) receptor states. |
| 4555 | 17306383 | Inhibition of CCK-stimulated increases in phospholipase C, PKC activity or intracellular calcium decreased PKD1 S916 phosphorylation by 56%, 62% and 96%, respectively. |
| 4556 | 17306383 | Inhibition of Src/PI3K/MAPK/tyrosine phosphorylation had no effect. |
| 4557 | 17306383 | These results demonstrate that CCK(A) receptor activation leads to PKD activation by signaling through PKC-dependent and PKC-independent pathways. |
| 4558 | 17307054 | The downregulation of the antiatherogenic phosphatidylinositol-3-kinase-mediated insulin receptor-signaling pathway, and maintained activity of the proatherogenic mitogenic-activated protein kinase pathway in insulin-resistant states, leads to accelerated atherosclerosis. |
| 4559 | 17313857 | [High D-glucose alters PI3K and Akt signaling and leads to endothelial cell migration, proliferation and angiogenesis dysfunction]. |
| 4560 | 17318772 | Insulin causes a transient induction of proliferation via activation of the PI3-kinase pathway in airway smooth muscle cells. |
| 4561 | 17318772 | In ASM cells, insulin activated the phosphatidylinositol 3-kinase (PI3 K) pathway, while FBS activated both PI3 K and the mitogen-activated protein kinase (MAPK) pathway. |
| 4562 | 17318772 | The PI3K pathway inhibitors LY294002 and wortmannin abolished the stimulation of cell proliferation by insulin, indicating a role for this pathway in the cellular response to insulin. |
| 4563 | 17318772 | Insulin causes a transient induction of proliferation via activation of the PI3-kinase pathway in airway smooth muscle cells. |
| 4564 | 17318772 | In ASM cells, insulin activated the phosphatidylinositol 3-kinase (PI3 K) pathway, while FBS activated both PI3 K and the mitogen-activated protein kinase (MAPK) pathway. |
| 4565 | 17318772 | The PI3K pathway inhibitors LY294002 and wortmannin abolished the stimulation of cell proliferation by insulin, indicating a role for this pathway in the cellular response to insulin. |
| 4566 | 17346750 | In insulin-deficient STZ-diabetic rats, resveratrol significantly lowered the plasma glucose 90 min after oral treatment, and the hypoglycemic effect was abolished by phosphatidyl-3-kinase (PI3K) inhibitors (LY294002 and wortmannin) which also inhibited resveratrol-induced Akt phosphorylation in soleus muscle of STZ-diabetic rats. |
| 4567 | 17346750 | The change in the protein expression level of glucose transporter subtype 4 (GLUT4) in the soleus muscle and phosphoenolpyruvate carboxykinase (PEPCK) in the liver of STZ-diabetic rats treated with resveratrol (3 mg/kg, p.o.) for 7 days was examined. |
| 4568 | 17346750 | Resveratrol normalized hepatic PEPCK expression and increased GLUT4 expression in the soleus muscle of STZ-diabetic rats. |
| 4569 | 17346750 | The results indicate that the mechanisms contributing to the hypoglycemic effect of resveratrol include insulin-dependent and insulin-independent pathway, and PI3K-Akt-signaling was involved in the latter mechanism to enhance glucose uptake in skeletal muscle. |
| 4570 | 17346750 | In insulin-deficient STZ-diabetic rats, resveratrol significantly lowered the plasma glucose 90 min after oral treatment, and the hypoglycemic effect was abolished by phosphatidyl-3-kinase (PI3K) inhibitors (LY294002 and wortmannin) which also inhibited resveratrol-induced Akt phosphorylation in soleus muscle of STZ-diabetic rats. |
| 4571 | 17346750 | The change in the protein expression level of glucose transporter subtype 4 (GLUT4) in the soleus muscle and phosphoenolpyruvate carboxykinase (PEPCK) in the liver of STZ-diabetic rats treated with resveratrol (3 mg/kg, p.o.) for 7 days was examined. |
| 4572 | 17346750 | Resveratrol normalized hepatic PEPCK expression and increased GLUT4 expression in the soleus muscle of STZ-diabetic rats. |
| 4573 | 17346750 | The results indicate that the mechanisms contributing to the hypoglycemic effect of resveratrol include insulin-dependent and insulin-independent pathway, and PI3K-Akt-signaling was involved in the latter mechanism to enhance glucose uptake in skeletal muscle. |
| 4574 | 17353188 | Reduction of LMW-PTP expression with the ASO in cultured mouse hepatocytes and in liver and fat tissues of diet-induced obese (DIO) mice and ob/ob mice led to increased phosphorylation and activity of key insulin signaling intermediates, including insulin receptor-beta subunit, phosphatidylinositol 3-kinase, and Akt in response to insulin stimulation. |
| 4575 | 17363366 | Specific knockdown of Fyn (but not Src) with small interfering RNA inhibited both EGCG-stimulated phosphorylation of Akt and eNOS as well as production of NO in BAEC. |
| 4576 | 17363366 | Treatment of BAEC with EGCG generated intracellular H(2)O(2) (assessed with H(2)O(2)-specific fluorescent dye CM-H(2)DCF-DA), whereas treatment with N-acetylcysteine inhibited EGCG-stimulated phosphorylation of Fyn, Akt, and eNOS. |
| 4577 | 17363366 | We conclude that EGCG has endothelial-dependent vasodilator actions mediated by intracellular signaling pathways requiring reactive oxygen species and Fyn that lead to activation of phosphatidylinositol 3-kinase, Akt, and eNOS. |
| 4578 | 17363461 | Insulin-like growth factor-I provokes functional antagonism and internalization of beta1-adrenergic receptors. |
| 4579 | 17363461 | Hormones that activate receptor tyrosine kinases have been shown to regulate G protein-coupled receptors, and herein we investigate the ability of IGF-I to regulate the beta(1)-adrenergic receptor. |
| 4580 | 17363461 | Inhibiting either phosphatidylinositol 3-kinase or the serine/threonine protein kinase Akt blocks the ability of IGF-I to antagonize and to internalize beta(1)-adrenergic receptors. |
| 4581 | 17363461 | Mutation of one potential Akt substrate site Ser412Ala, but not another Ser312Ala, of the beta(1)-adrenergic receptor abolishes the ability of IGF-I to functionally antagonize and to sequester the beta(1)-adrenergic receptor. |
| 4582 | 17363741 | Interleukin (IL)-6 is a proinflammatory cytokine shown to modify insulin sensitivity. |
| 4583 | 17363741 | Elevated plasma levels of IL-6 are observed in insulin-resistant states. |
| 4584 | 17363741 | Thus, IL-6 has also been suggested to promote insulin-mediated glucose utilization. |
| 4585 | 17363741 | A 30-min pre-exposure to IL-6 did not affect insulin-stimulated glucose transport. |
| 4586 | 17363741 | IL-6 increased phosphorylation of STAT3 (signal transducer and activator of transcription 3; P < 0.05), AMP-activated protein kinase (P = 0.063), and p38 mitogen-activated protein kinase (P < 0.05) and reduced phosphorylation of S6 ribosomal protein (P < 0.05). |
| 4587 | 17363741 | In contrast, phosphorylation of protein kinase B/Akt, AS160 (Akt substrate of 160 kDa), and GSK3alpha/beta (glycogen synthase kinase 3alpha/beta) as well as insulin receptor substrate 1-associated phosphatidylinositol 3-kinase activity remained unaltered. |
| 4588 | 17363741 | Insulin-stimulated glucose transport and insulin signaling were unchanged after IL-6 exposure. |
| 4589 | 17371242 | Extracellular and subcellular regulation of the PI3K/Akt cassette: new mechanisms for controlling insulin and growth factor signalling. |
| 4590 | 17371242 | The PI3K (phosphoinositide 3-kinase)/Akt (also called protein kinase B) signalling cassette plays a central role in the response to growth factors, particularly insulin-like molecules, and its misregulation is a characteristic feature of diabetes and many forms of human cancer. |
| 4591 | 17371242 | Recent molecular genetic studies initiated in the fruitfly, Drosophila melanogaster, have highlighted two new cell-type-specific mechanisms regulating PI3K/Akt signalling and its downstream effects. |
| 4592 | 17371242 | Extracellular and subcellular regulation of the PI3K/Akt cassette: new mechanisms for controlling insulin and growth factor signalling. |
| 4593 | 17371242 | The PI3K (phosphoinositide 3-kinase)/Akt (also called protein kinase B) signalling cassette plays a central role in the response to growth factors, particularly insulin-like molecules, and its misregulation is a characteristic feature of diabetes and many forms of human cancer. |
| 4594 | 17371242 | Recent molecular genetic studies initiated in the fruitfly, Drosophila melanogaster, have highlighted two new cell-type-specific mechanisms regulating PI3K/Akt signalling and its downstream effects. |
| 4595 | 17371242 | Extracellular and subcellular regulation of the PI3K/Akt cassette: new mechanisms for controlling insulin and growth factor signalling. |
| 4596 | 17371242 | The PI3K (phosphoinositide 3-kinase)/Akt (also called protein kinase B) signalling cassette plays a central role in the response to growth factors, particularly insulin-like molecules, and its misregulation is a characteristic feature of diabetes and many forms of human cancer. |
| 4597 | 17371242 | Recent molecular genetic studies initiated in the fruitfly, Drosophila melanogaster, have highlighted two new cell-type-specific mechanisms regulating PI3K/Akt signalling and its downstream effects. |
| 4598 | 17391917 | Tat gp91ds, a chimeric peptide that inhibits NADPH oxidase activity, also failed to affect glucose uptake and we found no significant evidence of NADPH oxidase (subunits tested were Nox4, p22phox, gp91phox and p47phox mRNA) in skeletal muscle cells in culture. |
| 4599 | 17391917 | Detailed studies on L6 cells demonstrate that the increase of glucose uptake is via a mechanism independent of phosphoinositide-3 kinase (PI3K)/Akt but dependent on AMP-activated protein kinase (AMPK). |
| 4600 | 17400802 | After solubilization of the cells, insulin receptor kinase activity, tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1), IRS-1-associated phosphatidylinositol-3 kinase (PI3-kinase), PI3-kinase activity, Thr(308) phosphorlyation of Akt, amount of protein tyrosine phosphatase-epsilon (PTPepsilon), and glycogen synthase activity were determined. |
| 4601 | 17400802 | Incubation with PD151746 resulted in a significant reduction of insulin-stimulated glycogen synthesis compared with cells not pre-incubated with the calpain inhibitor (-PD: t(0), 4.90 +/- 1.20%; t(5), 5.90 +/- 1.02%; t(15), 5.29 +/- 0.95%; t(30), 5.60 +/- 1.10%; t(45), 5.52 +/- 0.90%; t(60), 5.67 +/- 0.97%;+PD: t(0), 4.56 +/- 1.10%; t(5), 6.16 +/- 1.05%; t(15), 7.52 +/- 1.09%; t(30), 7.68 +/- 1.10%; t(45), 8.28 +/- 0.89%; t(60), 7.69 +/- 0.98%; P < 0.05). |
| 4602 | 17400802 | These results in HepG2 cells suggest that calpains play a role in the hepatic regulation of insulin-stimulated glycogen synthesis independent of the PI3-kinase/Akt signaling pathway. |
| 4603 | 17403678 | The Lipoxin A4 receptor is coupled to SHP-2 activation: implications for regulation of receptor tyrosine kinases. |
| 4604 | 17403678 | Using site-directed mutagenesis of the cytosolic domain of the platelet-derived growth factor receptor beta (PDGFRbeta), we report that mutation of the sites for phosphatidylinositol 3-kinase (Tyr(740) and Tyr(751)) and SHP-2 (Tyr(763) and Tyr(1009)) recruitment specifically inhibit the effect of LXA(4) on the PDGFRbeta signaling; furthermore inhibition of SHP-2 expression with short interfering RNA constructs blocked the effect of LXA(4) on PDGFRbeta phosphorylation. |
| 4605 | 17403678 | We demonstrate that association of the PDGFRbeta with lipid raft microdomains renders it susceptible to LXA(4)-mediated dephosphorylation by possible reactivation of oxidatively inactivated SHP-2. |
| 4606 | 17446186 | Tumor necrosis factor-alpha induces insulin resistance in endothelial cells via a p38 mitogen-activated protein kinase-dependent pathway. |
| 4607 | 17446186 | Systemic infusion of TNF-alpha abrogates insulin's action to enhance skeletal muscle microvascular perfusion. |
| 4608 | 17446186 | In skeletal muscle TNF-alpha induces insulin resistance via the p38 MAPK pathway. |
| 4609 | 17446186 | To examine whether p38 MAPK also regulates TNF-alpha-induced vascular insulin resistance, bovine aortic endothelial cells (bAECs) were incubated+/-TNF-alpha (5 ng/ml) for 6 h in the presence or absence of SB203580 (p38 MAPK specific inhibitor, 10 microM) after serum starvation for 10 h. |
| 4610 | 17446186 | For the last 30 min, cells were treated+/-1 nM insulin, and insulin receptor substrate (IRS)-1, Akt, endothelial nitric oxide synthase (eNOS), p38 MAPK, ERK1/2, c-Jun N-terminal kinase, and AMP-activated protein kinase (AMPK) phosphorylation, and eNOS activity were measured. |
| 4611 | 17446186 | TNF-alpha increased p38 MAPK phosphorylation, potently stimulated IRS-1 serine phosphorylation, and blunted insulin-stimulated IRS-1 tyrosine and Akt phosphorylation and eNOS activity. |
| 4612 | 17446186 | TNF-alpha also potently stimulated the phosphorylation of ERK1/2 and AMPK. |
| 4613 | 17446186 | Treatment with SB203580 decreased p38 MAPK phosphorylation back to the baseline and restored insulin sensitivity of IRS-1 tyrosine and Akt phosphorylation and eNOS activity in TNF-alpha-treated bAECs without affecting TNF-alpha-induced ERK1/2 and AMPK phosphorylation. |
| 4614 | 17446186 | We conclude that in cultured bAECs, TNF-alpha induces insulin resistance in the phosphatidylinositol 3-kinase/Akt/eNOS pathway via a p38 MAPK-dependent mechanism and enhances ERK1/2 and AMPK phosphorylation independent of the p38 MAPK pathway. |
| 4615 | 17446186 | This differential modulation of TNF-alpha's actions by p38 MAPK suggests that p38 MAPK plays a key role in TNF-alpha-mediated vascular insulin resistance and may contribute to the generalized endothelial dysfunction seen in type 2 diabetes mellitus and the cardiometabolic syndrome. |
| 4616 | 17457328 | Chuang and colleagues demonstrate that hypertrophy in vitro is dependent on an increased phosphoinositide 3-kinase (PI3K) activity and is correlated with increased levels of p21(WAF1/Cip1), a cell-cycle regulator that was previously associated with renal fibrosis and sclerosis from nondiabetic causes. |
| 4617 | 17464184 | AMPK plays a central role in the regulation of glucose and lipid metabolism, and hence it is considered a novel therapeutic target for metabolic syndrome such as type 2 diabetes. t-RVT significantly induced glucose uptake in C2C12 cells, via AMPK activation, but not a phosphatidylinositol-3 kinase (PI-3 kinase) signal pathway. |
| 4618 | 17464184 | However, in the presence of insulin, t-RVT also potentiated the effect of insulin on glucose uptake via AMPK activation, which led to further activation of PI-3 kinase/Akt signal pathway. |
| 4619 | 17467844 | These insulin actions were modestly inhibited by the application of LY294002, the phosphatidylinositol 3-kinase (PI3-kinase) inhibitor, but not completely, suggesting that another mechanism is also involved. |
| 4620 | 17467844 | These results may suggest that the extent of AMPK activation may be a tool for insulin receptors to monitor blood glucose level, with which insulin-induced insulin receptor activation determines the way to go negatively or positively toward [Ca(2+)](c). |
| 4621 | 17490618 | Phosphorylation events implicating p38 and PI3K mediate tungstate-effects in MIN6 beta cells. |
| 4622 | 17490618 | Tungstate treatment induced phosphorylation and subsequent activation of p38 and PI3K which in turn are implicated in tungstate PDX-1 nuclear localization and activation. |
| 4623 | 17490618 | These results show a direct involvement of p38 and PI3K phosphorylation in the mechanism of action of tungstate in the beta cell. |
| 4624 | 17490618 | Phosphorylation events implicating p38 and PI3K mediate tungstate-effects in MIN6 beta cells. |
| 4625 | 17490618 | Tungstate treatment induced phosphorylation and subsequent activation of p38 and PI3K which in turn are implicated in tungstate PDX-1 nuclear localization and activation. |
| 4626 | 17490618 | These results show a direct involvement of p38 and PI3K phosphorylation in the mechanism of action of tungstate in the beta cell. |
| 4627 | 17490618 | Phosphorylation events implicating p38 and PI3K mediate tungstate-effects in MIN6 beta cells. |
| 4628 | 17490618 | Tungstate treatment induced phosphorylation and subsequent activation of p38 and PI3K which in turn are implicated in tungstate PDX-1 nuclear localization and activation. |
| 4629 | 17490618 | These results show a direct involvement of p38 and PI3K phosphorylation in the mechanism of action of tungstate in the beta cell. |
| 4630 | 17513702 | Effects of endurance exercise training on insulin signaling in human skeletal muscle: interactions at the level of phosphatidylinositol 3-kinase, Akt, and AS160. |
| 4631 | 17513702 | Protein content of Akt1/2 (55 +/- 17%, P < 0.05), AS160 (25 +/- 8%, P = 0.08), GLUT4 (52 +/- 19%, P < 0.001), hexokinase 2 (HK2) (197 +/- 40%, P < 0.001), and insulin-responsive aminopeptidase (65 +/- 15%, P < 0.001) increased in muscle in response to training. |
| 4632 | 17513702 | During hyperinsulinemia, activities of insulin receptor substrate-1 (IRS-1)-associated phosphatidylinositol 3-kinase (PI3-K) (P < 0.005), Akt1 (P < 0.05), Akt2 (P < 0.005), and glycogen synthase (GS) (percent I-form, P < 0.05) increased similarly in both trained and untrained muscle, consistent with increased phosphorylation of Akt Thr(308), Akt Ser(473), AS160, glycogen synthase kinase (GSK)-3alpha Ser(21), and GSK-3beta Ser(9) and decreased phosphorylation of GS site 3a+b (all P < 0.005). |
| 4633 | 17513702 | Interestingly, training improved insulin action on thigh blood flow, and, furthermore, in both basal and insulin-stimulated muscle tissue, activities of Akt1 and GS and phosphorylation of AS160 increased with training (all P < 0.05). |
| 4634 | 17513702 | In contrast, training reduced IRS-1-associated PI3-K activity (P < 0.05) in both basal and insulin-stimulated muscle tissue. |
| 4635 | 17513702 | Effects of endurance exercise training on insulin signaling in human skeletal muscle: interactions at the level of phosphatidylinositol 3-kinase, Akt, and AS160. |
| 4636 | 17513702 | Protein content of Akt1/2 (55 +/- 17%, P < 0.05), AS160 (25 +/- 8%, P = 0.08), GLUT4 (52 +/- 19%, P < 0.001), hexokinase 2 (HK2) (197 +/- 40%, P < 0.001), and insulin-responsive aminopeptidase (65 +/- 15%, P < 0.001) increased in muscle in response to training. |
| 4637 | 17513702 | During hyperinsulinemia, activities of insulin receptor substrate-1 (IRS-1)-associated phosphatidylinositol 3-kinase (PI3-K) (P < 0.005), Akt1 (P < 0.05), Akt2 (P < 0.005), and glycogen synthase (GS) (percent I-form, P < 0.05) increased similarly in both trained and untrained muscle, consistent with increased phosphorylation of Akt Thr(308), Akt Ser(473), AS160, glycogen synthase kinase (GSK)-3alpha Ser(21), and GSK-3beta Ser(9) and decreased phosphorylation of GS site 3a+b (all P < 0.005). |
| 4638 | 17513702 | Interestingly, training improved insulin action on thigh blood flow, and, furthermore, in both basal and insulin-stimulated muscle tissue, activities of Akt1 and GS and phosphorylation of AS160 increased with training (all P < 0.05). |
| 4639 | 17513702 | In contrast, training reduced IRS-1-associated PI3-K activity (P < 0.05) in both basal and insulin-stimulated muscle tissue. |
| 4640 | 17513702 | Effects of endurance exercise training on insulin signaling in human skeletal muscle: interactions at the level of phosphatidylinositol 3-kinase, Akt, and AS160. |
| 4641 | 17513702 | Protein content of Akt1/2 (55 +/- 17%, P < 0.05), AS160 (25 +/- 8%, P = 0.08), GLUT4 (52 +/- 19%, P < 0.001), hexokinase 2 (HK2) (197 +/- 40%, P < 0.001), and insulin-responsive aminopeptidase (65 +/- 15%, P < 0.001) increased in muscle in response to training. |
| 4642 | 17513702 | During hyperinsulinemia, activities of insulin receptor substrate-1 (IRS-1)-associated phosphatidylinositol 3-kinase (PI3-K) (P < 0.005), Akt1 (P < 0.05), Akt2 (P < 0.005), and glycogen synthase (GS) (percent I-form, P < 0.05) increased similarly in both trained and untrained muscle, consistent with increased phosphorylation of Akt Thr(308), Akt Ser(473), AS160, glycogen synthase kinase (GSK)-3alpha Ser(21), and GSK-3beta Ser(9) and decreased phosphorylation of GS site 3a+b (all P < 0.005). |
| 4643 | 17513702 | Interestingly, training improved insulin action on thigh blood flow, and, furthermore, in both basal and insulin-stimulated muscle tissue, activities of Akt1 and GS and phosphorylation of AS160 increased with training (all P < 0.05). |
| 4644 | 17513702 | In contrast, training reduced IRS-1-associated PI3-K activity (P < 0.05) in both basal and insulin-stimulated muscle tissue. |
| 4645 | 17513737 | Type 2 diabetes impairs insulin receptor substrate-2-mediated phosphatidylinositol 3-kinase activity in primary macrophages to induce a state of cytokine resistance to IL-4 in association with overexpression of suppressor of cytokine signaling-3. |
| 4646 | 17513737 | In this study, we report that normal IL-4-dependent elaboration of IL-1 receptor antagonist (IL-1RA) requires IRS-2-mediated PI3K activity in primary macrophages. |
| 4647 | 17513737 | We also show that macrophages isolated from obese/diabetic db/db mice have impaired IRS-2-mediated PI3K activity and constitutively overexpress suppressor of cytokine signaling (SOCS)-3, which impairs an important IL-4 anti-inflammatory function. |
| 4648 | 17513737 | Resident peritoneal macrophages were isolated from db/db mice and were found to constitutively overexpress IL-6 and were unable to elaborate IL-1RA in response to IL-4-like db/+ mouse macrophages. |
| 4649 | 17513737 | Inhibition of PI3K with wortmannin or blockage of IRS-2/PI3K complex formation with a cell permeable IRS-2-derived tyrosine phosphopeptide inhibited IL-4-dependent IL-1RA production in db/+ macrophages. |
| 4650 | 17513737 | Examination of IL-4 signaling in db/db macrophages revealed that IL-4-dependent IRS-2/PI3K complex formation and IRS-2 tyrosine phosphorylation was reduced compared with db/+ macrophages. |
| 4651 | 17513737 | SOCS-3/IL-4 receptor complexes, however, were increased in db/db mouse macrophages compared with db/+ mice macrophages as was db/db mouse macrophage SOCS-3 expression. |
| 4652 | 17513737 | These results indicate that in the db/db mouse model of T2D, macrophage expression of SOCS-3 is increased, and impaired IL-4-dependent IRS-2/PI3K formation induces a state of IL-4 resistance that disrupts IL-4-dependent production of IL-1RA. |
| 4653 | 17513737 | Type 2 diabetes impairs insulin receptor substrate-2-mediated phosphatidylinositol 3-kinase activity in primary macrophages to induce a state of cytokine resistance to IL-4 in association with overexpression of suppressor of cytokine signaling-3. |
| 4654 | 17513737 | In this study, we report that normal IL-4-dependent elaboration of IL-1 receptor antagonist (IL-1RA) requires IRS-2-mediated PI3K activity in primary macrophages. |
| 4655 | 17513737 | We also show that macrophages isolated from obese/diabetic db/db mice have impaired IRS-2-mediated PI3K activity and constitutively overexpress suppressor of cytokine signaling (SOCS)-3, which impairs an important IL-4 anti-inflammatory function. |
| 4656 | 17513737 | Resident peritoneal macrophages were isolated from db/db mice and were found to constitutively overexpress IL-6 and were unable to elaborate IL-1RA in response to IL-4-like db/+ mouse macrophages. |
| 4657 | 17513737 | Inhibition of PI3K with wortmannin or blockage of IRS-2/PI3K complex formation with a cell permeable IRS-2-derived tyrosine phosphopeptide inhibited IL-4-dependent IL-1RA production in db/+ macrophages. |
| 4658 | 17513737 | Examination of IL-4 signaling in db/db macrophages revealed that IL-4-dependent IRS-2/PI3K complex formation and IRS-2 tyrosine phosphorylation was reduced compared with db/+ macrophages. |
| 4659 | 17513737 | SOCS-3/IL-4 receptor complexes, however, were increased in db/db mouse macrophages compared with db/+ mice macrophages as was db/db mouse macrophage SOCS-3 expression. |
| 4660 | 17513737 | These results indicate that in the db/db mouse model of T2D, macrophage expression of SOCS-3 is increased, and impaired IL-4-dependent IRS-2/PI3K formation induces a state of IL-4 resistance that disrupts IL-4-dependent production of IL-1RA. |
| 4661 | 17513737 | Type 2 diabetes impairs insulin receptor substrate-2-mediated phosphatidylinositol 3-kinase activity in primary macrophages to induce a state of cytokine resistance to IL-4 in association with overexpression of suppressor of cytokine signaling-3. |
| 4662 | 17513737 | In this study, we report that normal IL-4-dependent elaboration of IL-1 receptor antagonist (IL-1RA) requires IRS-2-mediated PI3K activity in primary macrophages. |
| 4663 | 17513737 | We also show that macrophages isolated from obese/diabetic db/db mice have impaired IRS-2-mediated PI3K activity and constitutively overexpress suppressor of cytokine signaling (SOCS)-3, which impairs an important IL-4 anti-inflammatory function. |
| 4664 | 17513737 | Resident peritoneal macrophages were isolated from db/db mice and were found to constitutively overexpress IL-6 and were unable to elaborate IL-1RA in response to IL-4-like db/+ mouse macrophages. |
| 4665 | 17513737 | Inhibition of PI3K with wortmannin or blockage of IRS-2/PI3K complex formation with a cell permeable IRS-2-derived tyrosine phosphopeptide inhibited IL-4-dependent IL-1RA production in db/+ macrophages. |
| 4666 | 17513737 | Examination of IL-4 signaling in db/db macrophages revealed that IL-4-dependent IRS-2/PI3K complex formation and IRS-2 tyrosine phosphorylation was reduced compared with db/+ macrophages. |
| 4667 | 17513737 | SOCS-3/IL-4 receptor complexes, however, were increased in db/db mouse macrophages compared with db/+ mice macrophages as was db/db mouse macrophage SOCS-3 expression. |
| 4668 | 17513737 | These results indicate that in the db/db mouse model of T2D, macrophage expression of SOCS-3 is increased, and impaired IL-4-dependent IRS-2/PI3K formation induces a state of IL-4 resistance that disrupts IL-4-dependent production of IL-1RA. |
| 4669 | 17513737 | Type 2 diabetes impairs insulin receptor substrate-2-mediated phosphatidylinositol 3-kinase activity in primary macrophages to induce a state of cytokine resistance to IL-4 in association with overexpression of suppressor of cytokine signaling-3. |
| 4670 | 17513737 | In this study, we report that normal IL-4-dependent elaboration of IL-1 receptor antagonist (IL-1RA) requires IRS-2-mediated PI3K activity in primary macrophages. |
| 4671 | 17513737 | We also show that macrophages isolated from obese/diabetic db/db mice have impaired IRS-2-mediated PI3K activity and constitutively overexpress suppressor of cytokine signaling (SOCS)-3, which impairs an important IL-4 anti-inflammatory function. |
| 4672 | 17513737 | Resident peritoneal macrophages were isolated from db/db mice and were found to constitutively overexpress IL-6 and were unable to elaborate IL-1RA in response to IL-4-like db/+ mouse macrophages. |
| 4673 | 17513737 | Inhibition of PI3K with wortmannin or blockage of IRS-2/PI3K complex formation with a cell permeable IRS-2-derived tyrosine phosphopeptide inhibited IL-4-dependent IL-1RA production in db/+ macrophages. |
| 4674 | 17513737 | Examination of IL-4 signaling in db/db macrophages revealed that IL-4-dependent IRS-2/PI3K complex formation and IRS-2 tyrosine phosphorylation was reduced compared with db/+ macrophages. |
| 4675 | 17513737 | SOCS-3/IL-4 receptor complexes, however, were increased in db/db mouse macrophages compared with db/+ mice macrophages as was db/db mouse macrophage SOCS-3 expression. |
| 4676 | 17513737 | These results indicate that in the db/db mouse model of T2D, macrophage expression of SOCS-3 is increased, and impaired IL-4-dependent IRS-2/PI3K formation induces a state of IL-4 resistance that disrupts IL-4-dependent production of IL-1RA. |
| 4677 | 17513737 | Type 2 diabetes impairs insulin receptor substrate-2-mediated phosphatidylinositol 3-kinase activity in primary macrophages to induce a state of cytokine resistance to IL-4 in association with overexpression of suppressor of cytokine signaling-3. |
| 4678 | 17513737 | In this study, we report that normal IL-4-dependent elaboration of IL-1 receptor antagonist (IL-1RA) requires IRS-2-mediated PI3K activity in primary macrophages. |
| 4679 | 17513737 | We also show that macrophages isolated from obese/diabetic db/db mice have impaired IRS-2-mediated PI3K activity and constitutively overexpress suppressor of cytokine signaling (SOCS)-3, which impairs an important IL-4 anti-inflammatory function. |
| 4680 | 17513737 | Resident peritoneal macrophages were isolated from db/db mice and were found to constitutively overexpress IL-6 and were unable to elaborate IL-1RA in response to IL-4-like db/+ mouse macrophages. |
| 4681 | 17513737 | Inhibition of PI3K with wortmannin or blockage of IRS-2/PI3K complex formation with a cell permeable IRS-2-derived tyrosine phosphopeptide inhibited IL-4-dependent IL-1RA production in db/+ macrophages. |
| 4682 | 17513737 | Examination of IL-4 signaling in db/db macrophages revealed that IL-4-dependent IRS-2/PI3K complex formation and IRS-2 tyrosine phosphorylation was reduced compared with db/+ macrophages. |
| 4683 | 17513737 | SOCS-3/IL-4 receptor complexes, however, were increased in db/db mouse macrophages compared with db/+ mice macrophages as was db/db mouse macrophage SOCS-3 expression. |
| 4684 | 17513737 | These results indicate that in the db/db mouse model of T2D, macrophage expression of SOCS-3 is increased, and impaired IL-4-dependent IRS-2/PI3K formation induces a state of IL-4 resistance that disrupts IL-4-dependent production of IL-1RA. |
| 4685 | 17513737 | Type 2 diabetes impairs insulin receptor substrate-2-mediated phosphatidylinositol 3-kinase activity in primary macrophages to induce a state of cytokine resistance to IL-4 in association with overexpression of suppressor of cytokine signaling-3. |
| 4686 | 17513737 | In this study, we report that normal IL-4-dependent elaboration of IL-1 receptor antagonist (IL-1RA) requires IRS-2-mediated PI3K activity in primary macrophages. |
| 4687 | 17513737 | We also show that macrophages isolated from obese/diabetic db/db mice have impaired IRS-2-mediated PI3K activity and constitutively overexpress suppressor of cytokine signaling (SOCS)-3, which impairs an important IL-4 anti-inflammatory function. |
| 4688 | 17513737 | Resident peritoneal macrophages were isolated from db/db mice and were found to constitutively overexpress IL-6 and were unable to elaborate IL-1RA in response to IL-4-like db/+ mouse macrophages. |
| 4689 | 17513737 | Inhibition of PI3K with wortmannin or blockage of IRS-2/PI3K complex formation with a cell permeable IRS-2-derived tyrosine phosphopeptide inhibited IL-4-dependent IL-1RA production in db/+ macrophages. |
| 4690 | 17513737 | Examination of IL-4 signaling in db/db macrophages revealed that IL-4-dependent IRS-2/PI3K complex formation and IRS-2 tyrosine phosphorylation was reduced compared with db/+ macrophages. |
| 4691 | 17513737 | SOCS-3/IL-4 receptor complexes, however, were increased in db/db mouse macrophages compared with db/+ mice macrophages as was db/db mouse macrophage SOCS-3 expression. |
| 4692 | 17513737 | These results indicate that in the db/db mouse model of T2D, macrophage expression of SOCS-3 is increased, and impaired IL-4-dependent IRS-2/PI3K formation induces a state of IL-4 resistance that disrupts IL-4-dependent production of IL-1RA. |
| 4693 | 17525361 | Phosphatidylinositol 3-kinase-dependent insulin-signaling pathways regulating endothelial production of nitric oxide share striking parallels with metabolic insulin-signaling pathways. |
| 4694 | 17525361 | Distinct MAPK-dependent insulin-signaling pathways (largely unrelated to metabolic actions of insulin) regulate secretion of the vasoconstrictor endothelin-1 from endothelium. |
| 4695 | 17525361 | Insulin resistance is characterized by pathway-specific impairment in phosphatidylinositol 3-kinase-dependent signaling that in vascular endothelium contributes to a reciprocal relationship between insulin resistance and endothelial dysfunction. |
| 4696 | 17525361 | Phosphatidylinositol 3-kinase-dependent insulin-signaling pathways regulating endothelial production of nitric oxide share striking parallels with metabolic insulin-signaling pathways. |
| 4697 | 17525361 | Distinct MAPK-dependent insulin-signaling pathways (largely unrelated to metabolic actions of insulin) regulate secretion of the vasoconstrictor endothelin-1 from endothelium. |
| 4698 | 17525361 | Insulin resistance is characterized by pathway-specific impairment in phosphatidylinositol 3-kinase-dependent signaling that in vascular endothelium contributes to a reciprocal relationship between insulin resistance and endothelial dysfunction. |
| 4699 | 17537841 | Physiological changes in extracellular glucose, insulin, and leptin regulate glucose-excited (GE) and glucose-inhibited (GI) neurons in the ventromedial hypothalamus (VMH). |
| 4700 | 17537841 | We previously showed that glucose and leptin inhibit NO production via the AMP-activated protein kinase (AMPK) pathway, while insulin stimulates NO production via the phosphatidylinositol-3-OH kinase (PI3K) pathway in VMH GI neurons. |
| 4701 | 17537841 | Hyperglycemia-induced inhibition of AMPK reduces PI3K signaling by activating the mammalian target of rapamycin (mTOR). |
| 4702 | 17537841 | Glucose- and insulin-regulated NO production was restored in the presence of the AMPK activator, 5-aminoimidazole-4-carboxamide-1-b-4-ribofuranoside or the mTOR inhibitor rapamycin. |
| 4703 | 17537841 | These data suggest that hyperglycemia impairs glucose and insulin regulation of NO production through AMPK inhibition. |
| 4704 | 17537841 | Physiological changes in extracellular glucose, insulin, and leptin regulate glucose-excited (GE) and glucose-inhibited (GI) neurons in the ventromedial hypothalamus (VMH). |
| 4705 | 17537841 | We previously showed that glucose and leptin inhibit NO production via the AMP-activated protein kinase (AMPK) pathway, while insulin stimulates NO production via the phosphatidylinositol-3-OH kinase (PI3K) pathway in VMH GI neurons. |
| 4706 | 17537841 | Hyperglycemia-induced inhibition of AMPK reduces PI3K signaling by activating the mammalian target of rapamycin (mTOR). |
| 4707 | 17537841 | Glucose- and insulin-regulated NO production was restored in the presence of the AMPK activator, 5-aminoimidazole-4-carboxamide-1-b-4-ribofuranoside or the mTOR inhibitor rapamycin. |
| 4708 | 17537841 | These data suggest that hyperglycemia impairs glucose and insulin regulation of NO production through AMPK inhibition. |
| 4709 | 17556534 | Moreover, by detecting the activation of the phosphatidylinositol 3-kinase and MAP kinase (MAPK) pathways, we found that oleate promoted the activation of extracellular signal-regulated protein kinase-MAPK pathway mainly via GPR40, increased the expression of early growth response gene-1, leading to the anti-lipoapoptotic effect on NIT-1 cells. |
| 4710 | 17567939 | Insulin causes renal dopamine D1 receptor desensitization via GRK2-mediated receptor phosphorylation involving phosphatidylinositol 3-kinase and protein kinase C. |
| 4711 | 17567939 | Insulin increased protein kinase C (PKC) activity and caused G protein-coupled receptor kinase 2 (GRK2) translocation to the membranes. |
| 4712 | 17567939 | Tyrosine kinase inhibitor genistein and phosphatidylinositol 3-kinase (PI3K) inhibitor wortmannin blocked insulin-mediated PKC activation and GRK2 membranous translocation. |
| 4713 | 17567939 | In conclusion, insulin-induced D1R desensitization involves PI3K, PKC, and GRK2. |
| 4714 | 17567939 | Insulin causes renal dopamine D1 receptor desensitization via GRK2-mediated receptor phosphorylation involving phosphatidylinositol 3-kinase and protein kinase C. |
| 4715 | 17567939 | Insulin increased protein kinase C (PKC) activity and caused G protein-coupled receptor kinase 2 (GRK2) translocation to the membranes. |
| 4716 | 17567939 | Tyrosine kinase inhibitor genistein and phosphatidylinositol 3-kinase (PI3K) inhibitor wortmannin blocked insulin-mediated PKC activation and GRK2 membranous translocation. |
| 4717 | 17567939 | In conclusion, insulin-induced D1R desensitization involves PI3K, PKC, and GRK2. |
| 4718 | 17567939 | Insulin causes renal dopamine D1 receptor desensitization via GRK2-mediated receptor phosphorylation involving phosphatidylinositol 3-kinase and protein kinase C. |
| 4719 | 17567939 | Insulin increased protein kinase C (PKC) activity and caused G protein-coupled receptor kinase 2 (GRK2) translocation to the membranes. |
| 4720 | 17567939 | Tyrosine kinase inhibitor genistein and phosphatidylinositol 3-kinase (PI3K) inhibitor wortmannin blocked insulin-mediated PKC activation and GRK2 membranous translocation. |
| 4721 | 17567939 | In conclusion, insulin-induced D1R desensitization involves PI3K, PKC, and GRK2. |
| 4722 | 17569617 | Specifically, EGCG regulates expression of VEGF, matrix metalloproteinases, uPA, IGF-1, EGFR, cell cycle regulatory proteins and inhibits NFk B, PI3-K/Akt, Ras/Raf/MAPK and AP-1 signaling pathways, thereby causing strong cancer chemopreventive effects. |
| 4723 | 17571165 | Overexpression of uncoupling protein 3 in skeletal muscle protects against fat-induced insulin resistance. |
| 4724 | 17571165 | We therefore hypothesized that overexpression of UCP3 in skeletal muscle might protect against fat-induced insulin resistance in muscle by conversion of intramyocellular fat into thermal energy. |
| 4725 | 17571165 | Insulin resistance in these tissues was associated with reduced insulin-stimulated insulin receptor substrate 1- (IRS-1-) and IRS-2-associated PI3K activity in muscle and liver, respectively. |
| 4726 | 17571165 | In contrast, UCP3-overexpressing mice were completely protected against fat-induced defects in insulin signaling and action in these tissues. |
| 4727 | 17582297 | [Aortic endothelium-dependent vasodilation function and PI3K-, PKB-, eNOS mRNA expressions in insulin-resistant and type 2 diabetic rats]. |
| 4728 | 17644513 | By metabolic labeling, we here identify phosphatidylinositol 3-phosphate as the sole in vivo product of the insulin-dependent activation of PI3K-C2alpha, confirming the emerging role of such a phosphoinositide in signaling. |
| 4729 | 17644513 | This is the first report showing a membrane targeting-mediated mechanism of activation for PI3K-C2alpha and that a small GTP-binding protein can activate a class II PI3K isoform. |
| 4730 | 17644513 | We also demonstrate that PI3K-C2alpha contributes to maximal insulin-induced translocation of the glucose transporter GLUT4 to the plasma membrane and subsequent glucose uptake, definitely assessing the role of this enzyme in insulin signaling. |
| 4731 | 17647198 | The Src homology 2 domain tyrosine phosphatases SHP-1 and SHP-2: diversified control of cell growth, inflammation, and injury. |
| 4732 | 17647198 | In particular, two cytoplasmic protein tyrosine phosphatases composed of two Src homology 2 (SH2) NH2-terminal domains and a C-terminal protein-tyrosine phosphatase domain referred to as SHP-1 and SHP-2 are known to govern a host of cellular functions. |
| 4733 | 17647198 | SHP-1 and SHP-2 modulate progenitor cell development, cellular growth, tissue inflammation, and cellular chemotaxis, but more recently the role of SHP-1 and SHP-2 to directly control cell survival involving oxidative stress pathways has come to light. |
| 4734 | 17647198 | SHP-1 and SHP-2 are fundamental for the function of several growth factor and metabolic pathways yielding far reaching implications for disease pathways and disorders such as diabetes, neurodegeneration, and cancer. |
| 4735 | 17647198 | Although SHP-1 and SHP-2 can employ similar or parallel cellular pathways, these proteins also clearly exert opposing effects upon downstream cellular cascades that affect early and late apoptotic programs. |
| 4736 | 17647198 | SHP-1 and SHP-2 modulate cellular signals that involve phosphatidylinositol 3-kinase, Akt, Janus kinase 2, signal transducer and activator of transcription proteins, mitogen-activating protein kinases, extracellular signal-related kinases, c-Jun-amino terminal kinases, and nuclear factor-kappaB. |
| 4737 | 17647198 | Our progressive understanding of the impact of SHP-1 and SHP-2 upon multiple cellular environments and organ systems should continue to facilitate the targeted development of treatments for a variety of disease entities. |
| 4738 | 17652185 | We characterized these PI3K products in insulin-secreting HIT T15 cells and were able to demonstrate, for the first time the presence of phosphatidylinositol 3,5-bisphosphate [PtdIns(3,5)P(2)]. |
| 4739 | 17660951 | When 3T3-L1 adipocytes were treated directly with MG, the impaired insulin signaling was also observed, indicated by decreased insulin-induced insulin-receptor substrate-1 (IRS-1) tyrosine phosphorylation and the decreased kinase activity of phosphatidylinositol (PI) 3-kinase (PI3K). |
| 4740 | 17660951 | The ability of NAC to block MG-impairment of PI3K activity and IRS-1 phosphorylation further confirmed the role of MG in the development of insulin resistance. |
| 4741 | 17660951 | When 3T3-L1 adipocytes were treated directly with MG, the impaired insulin signaling was also observed, indicated by decreased insulin-induced insulin-receptor substrate-1 (IRS-1) tyrosine phosphorylation and the decreased kinase activity of phosphatidylinositol (PI) 3-kinase (PI3K). |
| 4742 | 17660951 | The ability of NAC to block MG-impairment of PI3K activity and IRS-1 phosphorylation further confirmed the role of MG in the development of insulin resistance. |
| 4743 | 17664271 | Tumor necrosis factor receptor-1 can function through a G alpha q/11-beta-arrestin-1 signaling complex. |
| 4744 | 17664271 | It is well known that chronic TNFalpha exposure can lead to insulin resistance both in vitro and in vivo and that elevated blood levels of TNFalpha are observed in obese and/or diabetic individuals. |
| 4745 | 17664271 | We found that beta-arrestin-1 is associated with TRAF2 (TNF receptor-associated factor 2), an adaptor protein of TNF receptors, and that TNFalpha acutely stimulates tyrosine phosphorylation of G alpha(q/11) with an increase in G alpha(q/11) activity. |
| 4746 | 17664271 | Small interfering RNA-mediated knockdown of beta-arrestin-1 inhibits TNFalpha-induced tyrosine phosphorylation of G alpha(q/11) by interruption of Src kinase activation. |
| 4747 | 17664271 | TNFalpha stimulates lipolysis in 3T3-L1 adipocytes, and beta-arrestin-1 knockdown blocks the effects of TNFalpha to stimulate ERK activation and glycerol release. |
| 4748 | 17664271 | TNFalpha also led to activation of JNK with increased expression of the proinflammatory gene, monocyte chemoattractant protein-1 and matrix metalloproteinase 3, and beta-arrestin-1 knockdown inhibited both of these effects. |
| 4749 | 17664271 | Taken together these results reveal novel elements of TNFalpha action; 1) the trimeric G-protein component G alpha(q/11) and the adapter protein beta-arrestin-1 can function as signaling molecules in the TNFalpha action cascade; 2) beta-arrestin-1 can couple TNFalpha stimulation to ERK activation and lipolysis; 3) beta-arrestin-1 and G alpha(q/11) can mediate TNFalpha-induced phosphatidylinositol 3-kinase activation and inflammatory gene expression. |
| 4750 | 17694473 | Additionally, repeated myricetin treatments overturned the inability of insulin to increase the expression of glucose transporter subtype 4 (GLUT 4) and to increase the protein levels and phosphorylation of insulin receptor substrate-1 (IRS-1) in soleus muscle of these obese rats. |
| 4751 | 17694473 | The inability of insulin to increase expression of the p85 regulatory subunit of phosphatidylinositol 3-kinase (PI3-kinase) and to promote Akt serine phosphorylation in soleus muscle of these rats were also overturned by repeated myricetin treatments. |
| 4752 | 17694473 | These findings indicate that myricetin improves insulin sensitivity through increased post-receptor insulin signaling mediated by enhancements in IRS-1-associated PI3-kinase and GLUT 4 activity in muscles of obese Zucker rats. |
| 4753 | 17702846 | We have used U937 cells stably transfected to express luciferase under the control of NF-kappaB to examine if adiponectin may modulate NF-kappaB activity. |
| 4754 | 17702846 | Physiological concentrations of native adiponectin induced NF-kappaB activity. |
| 4755 | 17702846 | This effect was relatively strong compared with proinflammatory adipokines like leptin, resistin, and IL-6. |
| 4756 | 17702846 | The enhanced NF-kappaB activity was attributed to the high molecular weight adiponectin isoforms. |
| 4757 | 17702846 | NF-kappaB was not activated by mutated adiponectin that is unable to form high molecular weight complexes. |
| 4758 | 17702846 | Furthermore, the C-terminal fragment, globular adiponectin, markedly increased NF-kappaB reporter activity, cytokine release, and mRNA expression of inflammation marker genes, at higher levels than stimulation with TNF-alpha and lipopolysaccharide. |
| 4759 | 17702846 | NF-kappaB activation by globular adiponectin was not affected by antibody inhibition of toll-like receptor 4 or TNF receptors 1 and 2 but was attenuated by inhibitors of p38 MAPK, phosphatidylinositol 3-kinase, and protein kinase C. |
| 4760 | 17702846 | Analyses of the p65 subunit of NF-kappaB in different leukocyte cell lines showed activation of two monocytic cell lines (U937 and THP-1) by native and globular adiponectin. |
| 4761 | 17716867 | Alpha-linolenic acid attenuates high glucose-induced apoptosis in cultured human umbilical vein endothelial cells via PI3K/Akt/eNOS pathway. |
| 4762 | 17728393 | Our current study demonstrates: 1) leptin is a potent chemoattractant for monocytes and macrophages, inducing maximal chemotactic responses at 1 ng/ml; 2) leptin-mediated chemotaxis requires the presence of full-length leptin receptors on migrating cells; 3) leptin causes increased influx of intracellular calcium in macrophages; and 4) activation of janus kinase/signal transducers and activators of transduction (JAK/STAT), mitogen-activated protein kinase (MAPK), and phosphatidylinositol 3-kinase (PI3K) pathways are all necessary for leptin-induced macrophage migration. |
| 4763 | 17827708 | Role of phosphatidylinositol 3-kinase activation on insulin action and its alteration in diabetic conditions. |
| 4764 | 17827708 | Activation of PI (phosphatidylinositol) 3-kinase is essential for aspects of insulin-induced glucose metabolism, including translocation of GLUT4 to the cell surface and glycogen synthesis. |
| 4765 | 17827708 | The enzyme exists as a heterodimer containing a regulatory subunit and one of two widely-distributed isoforms of the p110 catalytic subunit: p110alpha or p110beta. |
| 4766 | 17827708 | Activation of PI 3-kinase and its downstream AKT has been demonstrated to be essential for almost all of the insulin-induced glucose and lipid metabolism such as glucose uptake, glycogen synthesis, suppression of glucose output and triglyceride synthesis as well as insulin-induced mitogenesis. |
| 4767 | 17827708 | In the obesity-induced insulin resistant condition, JNK and p70S6K are activated and phosphorylate IRS-proteins, which diminishes the insulin-induced tyrosine phosphorylation of IRS-proteins and thereby impairs the PI 3-kinase/AKT activations. |
| 4768 | 17827708 | Thus, the drugs which restore the impaired insulin-induced PI 3-kinase/AKT activation, for example, by suppressing JNK or p70S6K, PTEN or SHIP2, could be novel agents to treat diabetes mellitus. |
| 4769 | 17827708 | Role of phosphatidylinositol 3-kinase activation on insulin action and its alteration in diabetic conditions. |
| 4770 | 17827708 | Activation of PI (phosphatidylinositol) 3-kinase is essential for aspects of insulin-induced glucose metabolism, including translocation of GLUT4 to the cell surface and glycogen synthesis. |
| 4771 | 17827708 | The enzyme exists as a heterodimer containing a regulatory subunit and one of two widely-distributed isoforms of the p110 catalytic subunit: p110alpha or p110beta. |
| 4772 | 17827708 | Activation of PI 3-kinase and its downstream AKT has been demonstrated to be essential for almost all of the insulin-induced glucose and lipid metabolism such as glucose uptake, glycogen synthesis, suppression of glucose output and triglyceride synthesis as well as insulin-induced mitogenesis. |
| 4773 | 17827708 | In the obesity-induced insulin resistant condition, JNK and p70S6K are activated and phosphorylate IRS-proteins, which diminishes the insulin-induced tyrosine phosphorylation of IRS-proteins and thereby impairs the PI 3-kinase/AKT activations. |
| 4774 | 17827708 | Thus, the drugs which restore the impaired insulin-induced PI 3-kinase/AKT activation, for example, by suppressing JNK or p70S6K, PTEN or SHIP2, could be novel agents to treat diabetes mellitus. |
| 4775 | 17827708 | Role of phosphatidylinositol 3-kinase activation on insulin action and its alteration in diabetic conditions. |
| 4776 | 17827708 | Activation of PI (phosphatidylinositol) 3-kinase is essential for aspects of insulin-induced glucose metabolism, including translocation of GLUT4 to the cell surface and glycogen synthesis. |
| 4777 | 17827708 | The enzyme exists as a heterodimer containing a regulatory subunit and one of two widely-distributed isoforms of the p110 catalytic subunit: p110alpha or p110beta. |
| 4778 | 17827708 | Activation of PI 3-kinase and its downstream AKT has been demonstrated to be essential for almost all of the insulin-induced glucose and lipid metabolism such as glucose uptake, glycogen synthesis, suppression of glucose output and triglyceride synthesis as well as insulin-induced mitogenesis. |
| 4779 | 17827708 | In the obesity-induced insulin resistant condition, JNK and p70S6K are activated and phosphorylate IRS-proteins, which diminishes the insulin-induced tyrosine phosphorylation of IRS-proteins and thereby impairs the PI 3-kinase/AKT activations. |
| 4780 | 17827708 | Thus, the drugs which restore the impaired insulin-induced PI 3-kinase/AKT activation, for example, by suppressing JNK or p70S6K, PTEN or SHIP2, could be novel agents to treat diabetes mellitus. |
| 4781 | 17919189 | The insulin receptor substrate-2/phosphoinositide 3-kinase (PI3K) pathway plays a critical role in the regulation of beta-cell mass and function, demonstrated both in vitro and in vivo. |
| 4782 | 17991427 | SH3 domain of the phosphatidylinositol 3-kinase regulatory subunit is responsible for the formation of a sequestration complex with insulin receptor substrate-1. |
| 4783 | 17991427 | Class IA phosphatidylinositol 3-kinase (PI 3-kinase), which is composed of a 110kDa catalytic subunit and a regulatory subunit, plays a key role in most insulin dependent cellular responses. |
| 4784 | 17991427 | To date, five mammalian regulatory subunit isoforms have been identified, including two 85kDa proteins (p85alpha and p85beta), two 55kDa proteins (p55gamma and p55alpha), and one 50kDa protein (p50alpha). |
| 4785 | 17991427 | Interestingly, in response to insulin, only p85alpha and p85beta redistributed to isolated foci in the cells, while both were present throughout the cytoplasm in quiescent cells. |
| 4786 | 17991427 | Immunofluorescent antibodies against endogenous IRS-1 revealed IRS-1 to be co-localized in the p85 foci in response to insulin. |
| 4787 | 17991427 | As both insulin receptors and p110alpha catalytic subunits were absent from these foci on immunofluorescence study, only p85 and IRS-1 were suggested to form a sequestration complex in response to insulin. |
| 4788 | 17991427 | To determine the domain responsible for IRS-1 complex formation, we prepared and overexpressed the SH3 domain deletion mutant of p85alpha in CHO-IR cells. |
| 4789 | 17991427 | SH3 domain of the phosphatidylinositol 3-kinase regulatory subunit is responsible for the formation of a sequestration complex with insulin receptor substrate-1. |
| 4790 | 17991427 | Class IA phosphatidylinositol 3-kinase (PI 3-kinase), which is composed of a 110kDa catalytic subunit and a regulatory subunit, plays a key role in most insulin dependent cellular responses. |
| 4791 | 17991427 | To date, five mammalian regulatory subunit isoforms have been identified, including two 85kDa proteins (p85alpha and p85beta), two 55kDa proteins (p55gamma and p55alpha), and one 50kDa protein (p50alpha). |
| 4792 | 17991427 | Interestingly, in response to insulin, only p85alpha and p85beta redistributed to isolated foci in the cells, while both were present throughout the cytoplasm in quiescent cells. |
| 4793 | 17991427 | Immunofluorescent antibodies against endogenous IRS-1 revealed IRS-1 to be co-localized in the p85 foci in response to insulin. |
| 4794 | 17991427 | As both insulin receptors and p110alpha catalytic subunits were absent from these foci on immunofluorescence study, only p85 and IRS-1 were suggested to form a sequestration complex in response to insulin. |
| 4795 | 17991427 | To determine the domain responsible for IRS-1 complex formation, we prepared and overexpressed the SH3 domain deletion mutant of p85alpha in CHO-IR cells. |
| 4796 | 17991427 | SH3 domain of the phosphatidylinositol 3-kinase regulatory subunit is responsible for the formation of a sequestration complex with insulin receptor substrate-1. |
| 4797 | 17991427 | Class IA phosphatidylinositol 3-kinase (PI 3-kinase), which is composed of a 110kDa catalytic subunit and a regulatory subunit, plays a key role in most insulin dependent cellular responses. |
| 4798 | 17991427 | To date, five mammalian regulatory subunit isoforms have been identified, including two 85kDa proteins (p85alpha and p85beta), two 55kDa proteins (p55gamma and p55alpha), and one 50kDa protein (p50alpha). |
| 4799 | 17991427 | Interestingly, in response to insulin, only p85alpha and p85beta redistributed to isolated foci in the cells, while both were present throughout the cytoplasm in quiescent cells. |
| 4800 | 17991427 | Immunofluorescent antibodies against endogenous IRS-1 revealed IRS-1 to be co-localized in the p85 foci in response to insulin. |
| 4801 | 17991427 | As both insulin receptors and p110alpha catalytic subunits were absent from these foci on immunofluorescence study, only p85 and IRS-1 were suggested to form a sequestration complex in response to insulin. |
| 4802 | 17991427 | To determine the domain responsible for IRS-1 complex formation, we prepared and overexpressed the SH3 domain deletion mutant of p85alpha in CHO-IR cells. |
| 4803 | 17991742 | c-Src is required for tropomyosin receptor kinase C (TrkC)-induced activation of the phosphatidylinositol 3-kinase (PI3K)-AKT pathway. |
| 4804 | 17991742 | TrkC expression leads to the constitutive activation of two major effector pathways, namely the Ras-MAP kinase (MAPK) mitogenic pathway and the phosphatidylinositol 3-kinase (PI3K)-AKT pathway mediating cell survival. |
| 4805 | 17991742 | Here we define some aspects of the molecular mechanisms regulating TrkC-dependent Ras-Erk1/2 and PI3K/Akt activation. |
| 4806 | 17991742 | We show that endogenous TrkC associated with c-Src in human and mouse cancer cells which express TrkC. |
| 4807 | 17991742 | Suppression of c-Src by RNA interference in highly metastatic 4T1 mammary cancer cells, which express endogenous TrkC, resulted in markedly decreased expression of cyclin D1 and suppression of activation of Ras-Erk1/2 and PI3K-Akt. |
| 4808 | 17991742 | Furthermore, in c-Src-deficient SYF cells, TrkC failed to activate the PI3K-Atk pathway, but not the Ras-Erk1/2 pathway. |
| 4809 | 17991742 | Therefore these data indicate that TrkC induces the PI3K-Akt cascade through the activation of c-Src. |
| 4810 | 17991742 | c-Src is required for tropomyosin receptor kinase C (TrkC)-induced activation of the phosphatidylinositol 3-kinase (PI3K)-AKT pathway. |
| 4811 | 17991742 | TrkC expression leads to the constitutive activation of two major effector pathways, namely the Ras-MAP kinase (MAPK) mitogenic pathway and the phosphatidylinositol 3-kinase (PI3K)-AKT pathway mediating cell survival. |
| 4812 | 17991742 | Here we define some aspects of the molecular mechanisms regulating TrkC-dependent Ras-Erk1/2 and PI3K/Akt activation. |
| 4813 | 17991742 | We show that endogenous TrkC associated with c-Src in human and mouse cancer cells which express TrkC. |
| 4814 | 17991742 | Suppression of c-Src by RNA interference in highly metastatic 4T1 mammary cancer cells, which express endogenous TrkC, resulted in markedly decreased expression of cyclin D1 and suppression of activation of Ras-Erk1/2 and PI3K-Akt. |
| 4815 | 17991742 | Furthermore, in c-Src-deficient SYF cells, TrkC failed to activate the PI3K-Atk pathway, but not the Ras-Erk1/2 pathway. |
| 4816 | 17991742 | Therefore these data indicate that TrkC induces the PI3K-Akt cascade through the activation of c-Src. |
| 4817 | 17991742 | c-Src is required for tropomyosin receptor kinase C (TrkC)-induced activation of the phosphatidylinositol 3-kinase (PI3K)-AKT pathway. |
| 4818 | 17991742 | TrkC expression leads to the constitutive activation of two major effector pathways, namely the Ras-MAP kinase (MAPK) mitogenic pathway and the phosphatidylinositol 3-kinase (PI3K)-AKT pathway mediating cell survival. |
| 4819 | 17991742 | Here we define some aspects of the molecular mechanisms regulating TrkC-dependent Ras-Erk1/2 and PI3K/Akt activation. |
| 4820 | 17991742 | We show that endogenous TrkC associated with c-Src in human and mouse cancer cells which express TrkC. |
| 4821 | 17991742 | Suppression of c-Src by RNA interference in highly metastatic 4T1 mammary cancer cells, which express endogenous TrkC, resulted in markedly decreased expression of cyclin D1 and suppression of activation of Ras-Erk1/2 and PI3K-Akt. |
| 4822 | 17991742 | Furthermore, in c-Src-deficient SYF cells, TrkC failed to activate the PI3K-Atk pathway, but not the Ras-Erk1/2 pathway. |
| 4823 | 17991742 | Therefore these data indicate that TrkC induces the PI3K-Akt cascade through the activation of c-Src. |
| 4824 | 17993259 | We show here that insulin stimulates cell proliferation and c-Myc expression in colon cancer cell lines HT29 and Caco-2, intestinal non-cancer cell line IEC-6, and primary fetal rat intestinal cell (FRIC) cultures. |
| 4825 | 17993259 | The effect of insulin was blocked by phosphoinositide-3 Kinase (PI3K) inhibition, but only partially attenuated by inhibition of Protein kinase B (PKB), indicating the existence of both PKB-dependent and -independent mechanisms. |
| 4826 | 17993259 | The PKB-dependent mechanism of insulin-stimulated c-Myc expression in HT29 cells was shown to involve the activation of mTOR in c-Myc translation. |
| 4827 | 17993259 | In the investigation of the PKB-independent mechanism, we found that insulin-induced nuclear translocation of beta-catenin (beta-cat), an effector of Wnt signaling. |
| 4828 | 17993259 | Finally, chromatin immunoprecipitation (ChIP) detected significant increases in the binding of beta-cat to two TCF binding sites of the human c-Myc promoter following insulin treatment. |
| 4829 | 17993259 | Our observations support the existence of crosstalk between insulin and Wnt signaling pathways, and suggest that the crosstalk involves a PKB-independent mechanism. |
| 4830 | 18006502 | Blocking Raf-1 activity using a specific Raf-1 inhibitor or dominant-negative Raf-1 mutants led to a time- and dose-dependent increase in cell death, assessed by real-time imaging of propidium iodide incorporation, TUNEL, PCR-enhanced DNA laddering, and Caspase-3 cleavage. |
| 4831 | 18006502 | Inhibiting Raf-1 in beta-cells led to a striking loss of Bad phosphorylation at serine 112 and an increase in the protein levels of both Bad and Bax. |
| 4832 | 18006502 | Conversely, acutely inhibiting phosphatidylinositol 3-kinase Akt had more modest effects on beta-cell death. |
| 4833 | 18032526 | AGE-receptor-1 counteracts cellular oxidant stress induced by AGEs via negative regulation of p66shc-dependent FKHRL1 phosphorylation. |
| 4834 | 18032526 | AGE-induced OS is suppressed by AGER1, an AGE-receptor that counteracts receptor for advanced glycation end products (RAGE) and epidermal growth factor receptor (EGFR)-mediated Shc/Ras signal activation, resulting in decreased OS. |
| 4835 | 18032526 | Akt, FKHRL1, and antioxidants; e.g., MnSOD, regulate OS. |
| 4836 | 18032526 | Stimulation of HEK293 cells with either AGE compound increased phosphorylation of Akt and FKHRL1 by approximately threefold in a redox-dependent manner. |
| 4837 | 18032526 | AGE-induced phosphorylation of FKHRL1 led to a 70% downregulation of MnSOD, an effect partially blocked by a phosphatidylinositol 3-kinase inhibitor (LY-294002) and strongly inhibited by an antioxidant (N-acetylcysteine). |
| 4838 | 18032526 | These studies point to a new pathway for the induction of OS by AGEs involving FKHRL1 inactivation and MnSOD suppression via Ser-36 phosphorylation of p66(shc) in human kidney cells. |
| 4839 | 18032797 | It was found that CCAAT/enhancer-binding protein-alpha (C/EBP-alpha) and C/EBP-beta regulated HSD11B2 transcription and that DHEA likely modulated the transcription of 11beta-HSD2 in a phosphatidylinositol-3 kinase/Akt-dependent manner by increasing C/EBP-beta mRNA and protein expression. |
| 4840 | 18032797 | Moreover, it is shown that C/EBP-alpha and C/EBP-beta differentially regulate the expression of 11beta-HSD1 and 11beta-HSD2. |
| 4841 | 18045951 | Adiponectin signals in prostate cancer cells through Akt to activate the mammalian target of rapamycin pathway. |
| 4842 | 18045951 | Adiponectin has received much attention due to its beneficial effects on insulin sensitivity, and epidemiologic studies have further shown an inverse association between adiponectin levels and risk for multiple tumors, which is independent of the IGF system or other risk factors. |
| 4843 | 18045951 | Previous studies have shown that adiponectin can activate AMP-activated protein kinase (AMPK) in myocytes, hepatocytes, and adipocytes, suggesting that adiponectin may suppress tumor development through AMPK activation and subsequent inhibition of mammalian target of rapamycin (mTOR). |
| 4844 | 18045951 | In the present study, we demonstrate that while adiponectin stimulates AMPK in phosphatase and tensin homolog deleted on chromosome ten (PTEN) deficient LNCaP prostate cancer cells, it also increases mTOR activity as assessed by phosphorylation of two downstream targets, p70 S6 kinase and ribosomal protein S6. |
| 4845 | 18045951 | This adiponectin stimulation of mTOR was mediated through phosphatidylinositol 3-kinase (PI3 kinase) and Akt activation. |
| 4846 | 18045951 | These results show that adiponectin can activate both AMPK and PI3 kinase/Akt pathways, and that cell type-specific factors such as PTEN status may determine which of these pathways will have the dominant effect on mTOR. |
| 4847 | 18160431 | Hepatitis C virus core protein upregulates serine phosphorylation of insulin receptor substrate-1 and impairs the downstream akt/protein kinase B signaling pathway for insulin resistance. |
| 4848 | 18160431 | Since we and others have previously observed that HCV core protein activates c-Jun N-terminal kinase (JNK) and mitogen-activated protein kinase, we examined the contribution of these pathways to insulin resistance in hepatocytes. |
| 4849 | 18160431 | HCV core protein-mediated Ser(312) phosphorylation of IRS-1 was inhibited by JNK (SP600125) and phosphatidylinositol-3 kinase (LY294002) inhibitors. |
| 4850 | 18160431 | Taken together, our results demonstrated that HCV core protein increases IRS-1 phosphorylation at Ser(312) which may contribute in part to the mechanism of insulin resistance. |
| 4851 | 18162514 | The effects of OXA on cAMP, adenylate-cyclase-kinase (AKT), phosphoinositide-dependent kinase (PDK)-1, forkhead box O-1 (Foxo1), and cAMP response element-binding protein were measured by ELISA and Western blot. |
| 4852 | 18162514 | OXA decreased cAMP and Ca(2+)(i) concentration and increased AKT, PDK-1, and Foxo1 phosphorylation. |
| 4853 | 18162514 | OXA increases AKT/PDK-1 phosphorylation and inhibits proglucagon expression via phosphatidylinositol 3-kinase- and Foxo-1-dependent pathways. |
| 4854 | 18191647 | The current wisdom indicates that insulin's positive effects, normoglycemia, vasodilation, and anti-inflammation, are mediated by the canonical phosphoinositide 3-kinase (PI3K)/Akt pathway whereas the negative effects are mediated by the mitogen-activated protein kinase (MAPK)/extracellular regulated kinase (ERK) pathway. |
| 4855 | 18191647 | Much of the intracellular oxidant stress is mediated by the MAPK/ERK pathway which is a downstream signal also for other proatherogenic hormones such as angiotensin II. |
| 4856 | 18202124 | Protein kinase C-zeta phosphorylates insulin receptor substrate-1, -3, and -4 but not -2: isoform specific determinants of specificity in insulin signaling. |
| 4857 | 18202124 | Protein kinase C-zeta, a downstream effector of phosphatidylinositol 3-kinase (PI3K), phosphorylates insulin receptor substrate (IRS)-1 on serine residues impairing activation of PI3K in response to insulin. |
| 4858 | 18202124 | Because IRS-1 is upstream from PI3K, this represents a negative feedback mechanism that may contribute to signal specificity in insulin action. |
| 4859 | 18202124 | To determine whether similar feedback pathways exist for other IRS isoforms, we evaluated IRS-2, -3, and -4 as substrates for PKC-zeta. |
| 4860 | 18202124 | In an in vitro kinase assay, purified recombinant PKC-zeta phosphorylated IRS-1, -3 and -4 but not IRS-2. |
| 4861 | 18202124 | Similar results were obtained with an immune-complex kinase assay demonstrating that wild-type, but not kinase-deficient mutant PKC-zeta, phosphorylated IRS-1, -3, and -4 but not IRS-2. |
| 4862 | 18202124 | Insulin-stimulated IRS tyrosine phosphorylation was impaired by overepxression of PKC-zeta for IRS-1, -3, and -4 but not IRS-2. |
| 4863 | 18202124 | Significant insulin-stimulated increases in PI3K activity was coimmunoprecipitated with all IRS isoforms. |
| 4864 | 18202124 | In cells overexpressing PKC-zeta there was marked inhibition of insulin-stimulated PI3K activity associated with IRS-1, -3 and -4 but not IRS-2. |
| 4865 | 18202124 | That is, PI3K activity associated with IRS-2 in response to insulin was similar in control cells and cells overexpressing PKC-zeta. |
| 4866 | 18202124 | We conclude that IRS-3 and -4 are novel substrates for PKC-zeta that may participate in a negative feedback pathway for insulin signaling similar to IRS-1. |
| 4867 | 18202124 | The inability of PKC-zeta to phosphorylate IRS-2 may help determine specific functional roles for IRS-2. |
| 4868 | 18202124 | Protein kinase C-zeta phosphorylates insulin receptor substrate-1, -3, and -4 but not -2: isoform specific determinants of specificity in insulin signaling. |
| 4869 | 18202124 | Protein kinase C-zeta, a downstream effector of phosphatidylinositol 3-kinase (PI3K), phosphorylates insulin receptor substrate (IRS)-1 on serine residues impairing activation of PI3K in response to insulin. |
| 4870 | 18202124 | Because IRS-1 is upstream from PI3K, this represents a negative feedback mechanism that may contribute to signal specificity in insulin action. |
| 4871 | 18202124 | To determine whether similar feedback pathways exist for other IRS isoforms, we evaluated IRS-2, -3, and -4 as substrates for PKC-zeta. |
| 4872 | 18202124 | In an in vitro kinase assay, purified recombinant PKC-zeta phosphorylated IRS-1, -3 and -4 but not IRS-2. |
| 4873 | 18202124 | Similar results were obtained with an immune-complex kinase assay demonstrating that wild-type, but not kinase-deficient mutant PKC-zeta, phosphorylated IRS-1, -3, and -4 but not IRS-2. |
| 4874 | 18202124 | Insulin-stimulated IRS tyrosine phosphorylation was impaired by overepxression of PKC-zeta for IRS-1, -3, and -4 but not IRS-2. |
| 4875 | 18202124 | Significant insulin-stimulated increases in PI3K activity was coimmunoprecipitated with all IRS isoforms. |
| 4876 | 18202124 | In cells overexpressing PKC-zeta there was marked inhibition of insulin-stimulated PI3K activity associated with IRS-1, -3 and -4 but not IRS-2. |
| 4877 | 18202124 | That is, PI3K activity associated with IRS-2 in response to insulin was similar in control cells and cells overexpressing PKC-zeta. |
| 4878 | 18202124 | We conclude that IRS-3 and -4 are novel substrates for PKC-zeta that may participate in a negative feedback pathway for insulin signaling similar to IRS-1. |
| 4879 | 18202124 | The inability of PKC-zeta to phosphorylate IRS-2 may help determine specific functional roles for IRS-2. |
| 4880 | 18202124 | Protein kinase C-zeta phosphorylates insulin receptor substrate-1, -3, and -4 but not -2: isoform specific determinants of specificity in insulin signaling. |
| 4881 | 18202124 | Protein kinase C-zeta, a downstream effector of phosphatidylinositol 3-kinase (PI3K), phosphorylates insulin receptor substrate (IRS)-1 on serine residues impairing activation of PI3K in response to insulin. |
| 4882 | 18202124 | Because IRS-1 is upstream from PI3K, this represents a negative feedback mechanism that may contribute to signal specificity in insulin action. |
| 4883 | 18202124 | To determine whether similar feedback pathways exist for other IRS isoforms, we evaluated IRS-2, -3, and -4 as substrates for PKC-zeta. |
| 4884 | 18202124 | In an in vitro kinase assay, purified recombinant PKC-zeta phosphorylated IRS-1, -3 and -4 but not IRS-2. |
| 4885 | 18202124 | Similar results were obtained with an immune-complex kinase assay demonstrating that wild-type, but not kinase-deficient mutant PKC-zeta, phosphorylated IRS-1, -3, and -4 but not IRS-2. |
| 4886 | 18202124 | Insulin-stimulated IRS tyrosine phosphorylation was impaired by overepxression of PKC-zeta for IRS-1, -3, and -4 but not IRS-2. |
| 4887 | 18202124 | Significant insulin-stimulated increases in PI3K activity was coimmunoprecipitated with all IRS isoforms. |
| 4888 | 18202124 | In cells overexpressing PKC-zeta there was marked inhibition of insulin-stimulated PI3K activity associated with IRS-1, -3 and -4 but not IRS-2. |
| 4889 | 18202124 | That is, PI3K activity associated with IRS-2 in response to insulin was similar in control cells and cells overexpressing PKC-zeta. |
| 4890 | 18202124 | We conclude that IRS-3 and -4 are novel substrates for PKC-zeta that may participate in a negative feedback pathway for insulin signaling similar to IRS-1. |
| 4891 | 18202124 | The inability of PKC-zeta to phosphorylate IRS-2 may help determine specific functional roles for IRS-2. |
| 4892 | 18202124 | Protein kinase C-zeta phosphorylates insulin receptor substrate-1, -3, and -4 but not -2: isoform specific determinants of specificity in insulin signaling. |
| 4893 | 18202124 | Protein kinase C-zeta, a downstream effector of phosphatidylinositol 3-kinase (PI3K), phosphorylates insulin receptor substrate (IRS)-1 on serine residues impairing activation of PI3K in response to insulin. |
| 4894 | 18202124 | Because IRS-1 is upstream from PI3K, this represents a negative feedback mechanism that may contribute to signal specificity in insulin action. |
| 4895 | 18202124 | To determine whether similar feedback pathways exist for other IRS isoforms, we evaluated IRS-2, -3, and -4 as substrates for PKC-zeta. |
| 4896 | 18202124 | In an in vitro kinase assay, purified recombinant PKC-zeta phosphorylated IRS-1, -3 and -4 but not IRS-2. |
| 4897 | 18202124 | Similar results were obtained with an immune-complex kinase assay demonstrating that wild-type, but not kinase-deficient mutant PKC-zeta, phosphorylated IRS-1, -3, and -4 but not IRS-2. |
| 4898 | 18202124 | Insulin-stimulated IRS tyrosine phosphorylation was impaired by overepxression of PKC-zeta for IRS-1, -3, and -4 but not IRS-2. |
| 4899 | 18202124 | Significant insulin-stimulated increases in PI3K activity was coimmunoprecipitated with all IRS isoforms. |
| 4900 | 18202124 | In cells overexpressing PKC-zeta there was marked inhibition of insulin-stimulated PI3K activity associated with IRS-1, -3 and -4 but not IRS-2. |
| 4901 | 18202124 | That is, PI3K activity associated with IRS-2 in response to insulin was similar in control cells and cells overexpressing PKC-zeta. |
| 4902 | 18202124 | We conclude that IRS-3 and -4 are novel substrates for PKC-zeta that may participate in a negative feedback pathway for insulin signaling similar to IRS-1. |
| 4903 | 18202124 | The inability of PKC-zeta to phosphorylate IRS-2 may help determine specific functional roles for IRS-2. |
| 4904 | 18202124 | Protein kinase C-zeta phosphorylates insulin receptor substrate-1, -3, and -4 but not -2: isoform specific determinants of specificity in insulin signaling. |
| 4905 | 18202124 | Protein kinase C-zeta, a downstream effector of phosphatidylinositol 3-kinase (PI3K), phosphorylates insulin receptor substrate (IRS)-1 on serine residues impairing activation of PI3K in response to insulin. |
| 4906 | 18202124 | Because IRS-1 is upstream from PI3K, this represents a negative feedback mechanism that may contribute to signal specificity in insulin action. |
| 4907 | 18202124 | To determine whether similar feedback pathways exist for other IRS isoforms, we evaluated IRS-2, -3, and -4 as substrates for PKC-zeta. |
| 4908 | 18202124 | In an in vitro kinase assay, purified recombinant PKC-zeta phosphorylated IRS-1, -3 and -4 but not IRS-2. |
| 4909 | 18202124 | Similar results were obtained with an immune-complex kinase assay demonstrating that wild-type, but not kinase-deficient mutant PKC-zeta, phosphorylated IRS-1, -3, and -4 but not IRS-2. |
| 4910 | 18202124 | Insulin-stimulated IRS tyrosine phosphorylation was impaired by overepxression of PKC-zeta for IRS-1, -3, and -4 but not IRS-2. |
| 4911 | 18202124 | Significant insulin-stimulated increases in PI3K activity was coimmunoprecipitated with all IRS isoforms. |
| 4912 | 18202124 | In cells overexpressing PKC-zeta there was marked inhibition of insulin-stimulated PI3K activity associated with IRS-1, -3 and -4 but not IRS-2. |
| 4913 | 18202124 | That is, PI3K activity associated with IRS-2 in response to insulin was similar in control cells and cells overexpressing PKC-zeta. |
| 4914 | 18202124 | We conclude that IRS-3 and -4 are novel substrates for PKC-zeta that may participate in a negative feedback pathway for insulin signaling similar to IRS-1. |
| 4915 | 18202124 | The inability of PKC-zeta to phosphorylate IRS-2 may help determine specific functional roles for IRS-2. |
| 4916 | 18202127 | Insulin stimulates primary beta-cell proliferation via Raf-1 kinase. |
| 4917 | 18202127 | Elevating glucose from 5-15 mm did not significantly increase beta-cell replication. beta-Cell proliferation was inhibited by somatostatin as well as inhibitors of insulin signaling. |
| 4918 | 18202127 | Interestingly, inhibiting Raf-1 kinase blocked proliferation stimulated by low, but not high (superphysiological), insulin doses. |
| 4919 | 18202127 | Insulin-stimulated mouse insulinoma cell proliferation was dependent on both phosphatidylinositol 3-kinase/Akt and Raf-1/MAPK kinase pathways. |
| 4920 | 18202127 | Overexpression of Raf-1 was sufficient to increase proliferation in the absence of insulin, whereas a dominant-negative Raf-1 reduced proliferation in the presence of 200-pm insulin. |
| 4921 | 18202127 | Together, these results demonstrate for the first time that insulin, at levels that have been measured in vivo, can directly stimulate beta-cell proliferation and that Raf-1 kinase is involved in this process. |
| 4922 | 18220582 | The anti-apoptotic action of HGF was due to bcl-2-upregulation and the phosphatidylinositol 3-kinase pathway, which is involved in Akt activation. |
| 4923 | 18220582 | NADPH oxidase can be activated in hyperglycemia through the protein kinase C pathway. |
| 4924 | 18220582 | From the viewpoint of these molecular mechanisms, HMG-CoA reductase inhibitors (statins) might inhibit the high glucose-induced NADPH oxidase activation through inhibition of Rac activity and finally prevent the increase in ROS production in diabetes. |
| 4925 | 18287683 | Phosphatidylinositol (PI)-3 kinase (PI3K) and Akt are key signaling molecules in insulin and insulin-like growth factor-1 (IGF-1), which induce multiple biological effects in the heart such as cell survival and hypertrophy. |
| 4926 | 18287683 | Here, we have shown several fundamental techniques to study the role of PI3K and Akt in heart diseases. |
| 4927 | 18287683 | Phosphatidylinositol (PI)-3 kinase (PI3K) and Akt are key signaling molecules in insulin and insulin-like growth factor-1 (IGF-1), which induce multiple biological effects in the heart such as cell survival and hypertrophy. |
| 4928 | 18287683 | Here, we have shown several fundamental techniques to study the role of PI3K and Akt in heart diseases. |
| 4929 | 18288891 | Insulin resistance is characterized by impaired signaling through the insulin/insulin receptor/insulin receptor substrate/PI-3K/Akt pathway, leading to elevation of negatively regulated substrates such as glycogen synthase kinase-3beta (Gsk-3beta). |
| 4930 | 18288891 | In these studies, we designed experiments to determine the contribution of Gsk-3beta to regulation of beta-cell mass in two mouse models of insulin resistance. |
| 4931 | 18288891 | Crossing these mice with those having haploinsufficiency for Gsk-3beta (Gsk-3beta+/-) reduced insulin resistance by augmenting whole-body glucose disposal, and significantly reduced beta-cell mass. |
| 4932 | 18288891 | Preservation of beta-cell mass in Gsk-3beta+/- Irs2-/- mice was accompanied by suppressed p27(kip1) levels and increased Pdx1 levels. |
| 4933 | 18288891 | To separate peripheral versus beta-cell-specific effects of reduction of Gsk3beta activity on preservation of beta-cell mass, mice homozygous for a floxed Gsk-3beta allele (Gsk-3(F/F)) were then crossed with rat insulin promoter-Cre (RIP-Cre) mice to produce beta-cell-specific knockout of Gsk-3beta (betaGsk-3beta-/-). |
| 4934 | 18296638 | Overexpression of the dual-specificity phosphatase MKP-4/DUSP-9 protects against stress-induced insulin resistance. |
| 4935 | 18296638 | Insulin resistance, a hallmark of type 2 diabetes and obesity, is associated with increased activity of MAP and stress-activated protein (SAP) kinases, which results in decreased insulin signaling. |
| 4936 | 18296638 | Our goal was to investigate the role of MAP kinase phosphatase-4 (MKP-4) in modulating this process. |
| 4937 | 18296638 | We found that MKP-4 expression is up-regulated during adipocyte and myocyte differentiation in vitro and up-regulated during fasting in white adipose tissue in vivo. |
| 4938 | 18296638 | Overexpression of MKP-4 in 3T3-L1 cells inhibited ERK and JNK phosphorylation and, to a lesser extent, p38MAPK phosphorylation. |
| 4939 | 18296638 | As a result, the phosphorylation of IRS-1 serine 307 induced by anisomycin was abolished, leading to a sensitization of insulin signaling with recovery of insulin-stimulated IRS-1 tyrosine phosphorylation, IRS-1 docking with phosphatidylinositol 3-kinase, and Akt phosphorylation. |
| 4940 | 18296638 | MKP-4 also reversed the effect of TNF-alpha to inhibit insulin signaling; alter IL-6, Glut1 and Glut4 expression; and inhibit insulin-stimulated glucose uptake in 3T3-L1 adipocytes. |
| 4941 | 18296638 | Overexpression of MKP-4 in the liver of ob/ob mice decreased ERK and JNK phosphorylation, leading to a reduction in fed and fasted glycemia, improved glucose intolerance, decreased expression of gluconeogenic and lipogenic genes, and reduced hepatic steatosis. |
| 4942 | 18296638 | Thus, MKP-4 has a protective effect against the development of insulin resistance through its ability to dephosphorylate and inactivate crucial mediators of stress-induced insulin resistance, such as ERK and JNK, and increasing MKP-4 activity might provide a therapy for insulin-resistant disorders. |
| 4943 | 18303854 | The effect of 1 on glucose uptake was completely nullified by pretreatment with LY294002, an inhibitor of phosphoinositide 3-kinase (PI3K), and RO318220, an inhibitor of protein kinase C (PKC). |
| 4944 | 18370776 | In insulin resistant states and diabetes, heat shock factor 1(HSF-1) is low in insulin sensitive tissues, resulting in low Hsp 60, 70, and 90 levels. |
| 4945 | 18370776 | We propose that low Hsps levels are the result of decreased insulin action leading to less phosphorylation of PI3K, PKB, and glycogen synthase kinase-3 (GSK-3). |
| 4946 | 18370776 | Low Hsps make organs vulnerable to injury, impair the stress response, accelerate systemic inflammation, raise islet amyloid polypeptide, and increase insulin resistance. |
| 4947 | 18370776 | Support for the proposed "vicious" cycle is based on the observation that GSK-3 inhibition and Hsp stimulation result in increased insulin sensitivity, reduced accumulation of degenerative proteins with in the cell, improved wound healing, decreased organ damage and improved recovery from vascular ischemia. |
| 4948 | 18380932 | Telmisartan, an angiotensin II type 1 receptor blocker, inhibits advanced glycation end-product (AGE)-elicited hepatic insulin resistance via peroxisome proliferator-activated receptor-gamma activation. |
| 4949 | 18380932 | This study examined whether telmisartan, a unique angiotensin II type 1 receptor blocker (ARB) with peroxisome proliferator-activated receptor-gamma (PPAR-gamma)-modulating activity, improved insulin resistance in advanced glycation end-product (AGE)-exposed human hepatoma (Hep3B) cells. |
| 4950 | 18380932 | It also decreased tyrosine phosphorylation of IRS-1 and, subsequently, reduced the association of the p85 subunit of phosphatidylinositol 3-kinase with IRS-1 and glycogen synthesis in insulin-exposed Hep3B cells, all of which were inhibited by telmisartan. |
| 4951 | 18380932 | The insulin-sensitizing properties of telmisartan in AGE-exposed Hep3B cells were significantly blocked by GW9662, an inhibitor of PPAR-gamma. |
| 4952 | 18380932 | Our study suggests that telmisartan could improve AGE-elicited insulin resistance in Hep3B cells by inhibiting serine phosphorylation of IRS-1, at least in part, via activation of PPAR-gamma. |
| 4953 | 18387817 | Specifically, flavonoids and chalcones regulate expression of VEGF, matrix metalloproteinases (MMPs), EGFR and inhibit NFkappaB, PI3-K/Akt, ERK1/2 signalling pathways, thereby causing strong antiangiogenic effects. |
| 4954 | 18390897 | Among these molecular mechanisms, the phosphatidylinositol 3-kinase/protein kinase B (Akt) pathway is thought to play a crucial role. |
| 4955 | 18390897 | On the other hand, pharmacological modifications of parallel and interdependent signalling components, such as the AMP-activated protein kinase pathway, are now considered to be a good therapeutic approach to treat insulin-signalling defects such as insulin resistance and type-2 diabetes. |
| 4956 | 18395354 | Many biological molecules, such as ROS, IRS-1, PI3K, have been identified involving in the causes of insulin resistance. |
| 4957 | 18395354 | Presently, accumulative research data showed that BVR was a strong antioxidant enzyme, which could scavenge the excess ROS, and the characteristics of kinase activity and binding with p85 could modulate the biological function of IRS-1 and PI3K. |
| 4958 | 18395354 | We hypothesize that BVR has a significant role in the progression of insulin resistance, and it will be a promising therapeutic target for treating insulin resistance. |
| 4959 | 18395354 | Many biological molecules, such as ROS, IRS-1, PI3K, have been identified involving in the causes of insulin resistance. |
| 4960 | 18395354 | Presently, accumulative research data showed that BVR was a strong antioxidant enzyme, which could scavenge the excess ROS, and the characteristics of kinase activity and binding with p85 could modulate the biological function of IRS-1 and PI3K. |
| 4961 | 18395354 | We hypothesize that BVR has a significant role in the progression of insulin resistance, and it will be a promising therapeutic target for treating insulin resistance. |
| 4962 | 18407262 | The anorexic peptides insulin, leptin and the neurotransmitter serotonin share common signalling pathways involved in food intake, in particular the insulin receptor substrate, phosphatidylinositol-3-kinase (PI3K) pathway. |
| 4963 | 18437163 | Insulin-like growth factor-I protects cells from ER stress-induced apoptosis via enhancement of the adaptive capacity of endoplasmic reticulum. |
| 4964 | 18437163 | Here we demonstrate that human MCF-7 breast cancer cells, as well as murine NIH/3T3 fibroblasts, are rescued from ER stress-initiated apoptosis by insulin-like growth factor-I (IGF-I). |
| 4965 | 18437163 | IGF-I significantly augments the adaptive capacity of the ER by enhancing compensatory mechanisms such as the IRE1 alpha-, PERK- and ATF6-mediated arms of ER stress signalling. |
| 4966 | 18437163 | During ER stress, IGF-I stimulates translational recovery and induces expression of the key molecular chaperone protein Grp78/BiP, thereby enhancing the folding capacity of the ER and promoting recovery from ER stress. |
| 4967 | 18437163 | Application of signal transduction inhibitors of MEK (U1026), PI3K (LY294002 and wortmannin), JNK (SP600125), p38 (SB203580), protein kinases A and C (H-89 and staurosporine) and STAT3 (Stattic) does not prevent IGF-I-mediated protection from ER stress-induced apoptosis. |
| 4968 | 18475052 | Suppressive effects of glucagon-like peptide-1 on interferon-gamma-induced nitric oxide production in insulin-producing cells is mediated by inhibition of tumor necrosis factor-alpha production. |
| 4969 | 18475052 | We treated MIN6N8a mouse beta cells with interferon (IFN)-gamma in the presence or absence of GLP-1 and found that IFN-gamma treatment induced iNOS mRNA expression and NO production, which was significantly inhibited by treatment with GLP-1. |
| 4970 | 18475052 | Blocking of GLP-1 receptor signaling via the cyclic AMP and phosphatidylinositol 3-kinase pathway did not directly affect the suppressive effect of GLP-1 on IFN- gamma-induced iNOS mRNA expression. |
| 4971 | 18475052 | Further studies revealed that IFN-gamma induced the expression of TNF-alpha mRNA and protein, which synergistically induced NO production, and GLP-1 treatment inhibited this induction of TNF-alpha. |
| 4972 | 18475052 | To examine whether the reduction of TNF-alpha by GLP-1 treatment plays a role in suppressing NO production, we treated MIN6N8a cells with IFN-gamma in the presence of anti-TNF-alpha neutralizing antibody and found that NO production was reduced. |
| 4973 | 18475052 | In addition, treatment of mouse islets with GLP-1 inhibited the expression of iNOS and TNFmRNA. |
| 4974 | 18475052 | These results suggest that GLP-1 inhibits IFN-gamma-induced NO production by suppression of TNF-alpha production. |
| 4975 | 18493147 | Postreceptor crosstalk on PI3K/Akt between GH and insulin in non-catch-up growth rats born small for gestational age. |
| 4976 | 18495798 | We investigated the potential of PKB/Akt to mediate the profibrotic bioactions of TGF-beta1 in kidney. |
| 4977 | 18495798 | Treatment of normal rat kidney epithelial cells (NRK52E) with TGF-beta1 resulted in activation of phosphatidylinositol 3-kinase (PI3K) and PKB/Akt as evidenced by increased Ser473 phosphorylation and GSK-3beta phosphorylation. |
| 4978 | 18495798 | TGF-beta1 also stimulated increased Smad3 phosphorylation in these cells, a response that was insensitive to inhibition of PI3K or PKB/Akt. |
| 4979 | 18495798 | NRK52E cells displayed a loss of zona occludins 1 and E-cadherin and a gain in vimentin and alpha-smooth muscle actin expression, consistent with the fibrotic actions of TGF-beta1. |
| 4980 | 18495798 | These effects were blocked with inhibitors of PI3K and PKB/Akt. |
| 4981 | 18495798 | Furthermore, overexpression of PTEN, the lipid phosphatase regulator of PKB/Akt activation, inhibited TGF-beta1-induced PKB/Akt activation. |
| 4982 | 18495798 | Interestingly, in the Goto-Kakizaki rat model of type 2 diabetes, we also detected increased phosphorylation of PKB/Akt and its downstream target, GSK-3beta, in the tubules, relative to that in control Wistar rats. |
| 4983 | 18495798 | We investigated the potential of PKB/Akt to mediate the profibrotic bioactions of TGF-beta1 in kidney. |
| 4984 | 18495798 | Treatment of normal rat kidney epithelial cells (NRK52E) with TGF-beta1 resulted in activation of phosphatidylinositol 3-kinase (PI3K) and PKB/Akt as evidenced by increased Ser473 phosphorylation and GSK-3beta phosphorylation. |
| 4985 | 18495798 | TGF-beta1 also stimulated increased Smad3 phosphorylation in these cells, a response that was insensitive to inhibition of PI3K or PKB/Akt. |
| 4986 | 18495798 | NRK52E cells displayed a loss of zona occludins 1 and E-cadherin and a gain in vimentin and alpha-smooth muscle actin expression, consistent with the fibrotic actions of TGF-beta1. |
| 4987 | 18495798 | These effects were blocked with inhibitors of PI3K and PKB/Akt. |
| 4988 | 18495798 | Furthermore, overexpression of PTEN, the lipid phosphatase regulator of PKB/Akt activation, inhibited TGF-beta1-induced PKB/Akt activation. |
| 4989 | 18495798 | Interestingly, in the Goto-Kakizaki rat model of type 2 diabetes, we also detected increased phosphorylation of PKB/Akt and its downstream target, GSK-3beta, in the tubules, relative to that in control Wistar rats. |
| 4990 | 18495798 | We investigated the potential of PKB/Akt to mediate the profibrotic bioactions of TGF-beta1 in kidney. |
| 4991 | 18495798 | Treatment of normal rat kidney epithelial cells (NRK52E) with TGF-beta1 resulted in activation of phosphatidylinositol 3-kinase (PI3K) and PKB/Akt as evidenced by increased Ser473 phosphorylation and GSK-3beta phosphorylation. |
| 4992 | 18495798 | TGF-beta1 also stimulated increased Smad3 phosphorylation in these cells, a response that was insensitive to inhibition of PI3K or PKB/Akt. |
| 4993 | 18495798 | NRK52E cells displayed a loss of zona occludins 1 and E-cadherin and a gain in vimentin and alpha-smooth muscle actin expression, consistent with the fibrotic actions of TGF-beta1. |
| 4994 | 18495798 | These effects were blocked with inhibitors of PI3K and PKB/Akt. |
| 4995 | 18495798 | Furthermore, overexpression of PTEN, the lipid phosphatase regulator of PKB/Akt activation, inhibited TGF-beta1-induced PKB/Akt activation. |
| 4996 | 18495798 | Interestingly, in the Goto-Kakizaki rat model of type 2 diabetes, we also detected increased phosphorylation of PKB/Akt and its downstream target, GSK-3beta, in the tubules, relative to that in control Wistar rats. |
| 4997 | 18566119 | We recently identified insulin response element-binding protein-1 (IRE-BP1) as a transcription factor that binds and transactivates multiple insulin-responsive genes, but the regulation of IRE-BP1 in vivo is largely unknown. |
| 4998 | 18566119 | In this study, we show that IRE-BP1 interacts with the insulin response sequence of the IGF-I, IGFBP-1, and IGFBP-3 genes using chromatin immunoprecipitation assay. |
| 4999 | 18566119 | Furthermore, activation by IRE-BP1 is sequence specific and mimics that of the insulin effect on gene transcription. |
| 5000 | 18566119 | Tissue expression of IRE-BP1 is 50- to 200-fold higher in classical insulin target compared with nontarget tissues in lean animals, with a significantly reduced level of expression in the skeletal muscle and adipose tissue in obese and diabetic animals. |
| 5001 | 18566119 | Cytoplasmic sequestration appears to be related to inhibition of insulin-mediated phosphatidylinositol-3 kinase signaling. |
| 5002 | 18566119 | Therefore, in diabetes and obesity, the mechanisms involved in reducing the transactivation of the insulin response sequence by IRE-BP1 include decreased gene transcription and nuclear exclusion to prevent DNA binding. |
| 5003 | 18566119 | Our study supports the notion that IRE-BP1 may be relevant to the action of insulin in vivo and may play a role in the development of insulin resistance and diabetes. |
| 5004 | 18573875 | Increased insulin action in SKIP heterozygous knockout mice. |
| 5005 | 18573875 | Previous studies showed that SKIP negatively regulates insulin-induced phosphatidylinositol 3-kinase signaling (Ijuin and Takenawa, Mol. |
| 5006 | 18573875 | We now have generated mice with a targeted mutation of the mouse ortholog of the human SKIP gene, Pps. |
| 5007 | 18573875 | Adult heterozygous Pps mutant mice show increased insulin sensitivity and reduced diet-induced obesity with increased Akt/protein kinase B (PKB) phosphorylation in skeletal muscle but not in adipose tissue. |
| 5008 | 18573875 | The insulin-induced uptake of 2-deoxyglucose into the isolated soleus muscle was significantly enhanced in Pps mutant mice. |
| 5009 | 18573875 | Furthermore, in vitro knockdown studies in L6 myoblast cells revealed that reduction of SKIP expression level increased insulin-stimulated Akt/PKB phosphorylation and 2-deoxyglucose uptake. |
| 5010 | 18573875 | These results imply that SKIP regulates insulin signaling in skeletal muscle. |
| 5011 | 18573875 | Thus, SKIP may be a promising pharmacologic target for the treatment of insulin resistance and diabetes. |
| 5012 | 18575785 | In normal rats, exendin-4, like GLP-1 and insulin, enhanced glucose uptake. |
| 5013 | 18575785 | This effect, which is mediated to a certain extent by some kinases (PI3K/ PKB, p70s6k and MAPKs), may be caused by the peptide acting, at least in part, through the muscle GLP-1 receptors. |
| 5014 | 18575785 | Type 2 diabetic rats showed lower than normal basal muscle glucose transport and oxidation value, and higher glycogen synthase alpha activity and pyruvate release; however, no modification of glucose uptake by GLP-1 or exendin-4 was detected, at variance with insulin, and basal activity of PI3K/PKB was lower than normal, while that of p70s6k and MAPKs was higher. |
| 5015 | 18575785 | GLP-1 failed to affect the activity of any of the kinases, while exendin-4 increased the activity of PI3K, p70s6k and MAPKs, but not PKB, suggesting that this enzyme plays a major role in exendin-4 effect upon glucose transport in muscle. |
| 5016 | 18575785 | In normal rats, exendin-4, like GLP-1 and insulin, enhanced glucose uptake. |
| 5017 | 18575785 | This effect, which is mediated to a certain extent by some kinases (PI3K/ PKB, p70s6k and MAPKs), may be caused by the peptide acting, at least in part, through the muscle GLP-1 receptors. |
| 5018 | 18575785 | Type 2 diabetic rats showed lower than normal basal muscle glucose transport and oxidation value, and higher glycogen synthase alpha activity and pyruvate release; however, no modification of glucose uptake by GLP-1 or exendin-4 was detected, at variance with insulin, and basal activity of PI3K/PKB was lower than normal, while that of p70s6k and MAPKs was higher. |
| 5019 | 18575785 | GLP-1 failed to affect the activity of any of the kinases, while exendin-4 increased the activity of PI3K, p70s6k and MAPKs, but not PKB, suggesting that this enzyme plays a major role in exendin-4 effect upon glucose transport in muscle. |
| 5020 | 18575785 | In normal rats, exendin-4, like GLP-1 and insulin, enhanced glucose uptake. |
| 5021 | 18575785 | This effect, which is mediated to a certain extent by some kinases (PI3K/ PKB, p70s6k and MAPKs), may be caused by the peptide acting, at least in part, through the muscle GLP-1 receptors. |
| 5022 | 18575785 | Type 2 diabetic rats showed lower than normal basal muscle glucose transport and oxidation value, and higher glycogen synthase alpha activity and pyruvate release; however, no modification of glucose uptake by GLP-1 or exendin-4 was detected, at variance with insulin, and basal activity of PI3K/PKB was lower than normal, while that of p70s6k and MAPKs was higher. |
| 5023 | 18575785 | GLP-1 failed to affect the activity of any of the kinases, while exendin-4 increased the activity of PI3K, p70s6k and MAPKs, but not PKB, suggesting that this enzyme plays a major role in exendin-4 effect upon glucose transport in muscle. |
| 5024 | 18583936 | Leptin directly activates resident macrophages to form ADRP-enriched lipid droplets and enhances eicosanoid production via a mechanism that is dependent on activation of the PI3K/mTOR pathway. |
| 5025 | 18590692 | Here, we show that hepatic Irs1 and Irs2 function in a distinct manner in the regulation of glucose homeostasis. |
| 5026 | 18590692 | The PI3K activity associated with Irs2 began to increase during fasting, reached its peak immediately after refeeding, and decreased rapidly thereafter. |
| 5027 | 18590692 | By contrast, the PI3K activity associated with Irs1 began to increase a few hours after refeeding and reached its peak thereafter. |
| 5028 | 18590692 | The data indicate that Irs2 mainly functions during fasting and immediately after refeeding, and Irs1 functions primarily after refeeding. |
| 5029 | 18590692 | In fact, liver-specific Irs1-knockout mice failed to exhibit insulin resistance during fasting, but showed insulin resistance after refeeding; conversely, liver-specific Irs2-knockout mice displayed insulin resistance during fasting but not after refeeding. |
| 5030 | 18590692 | We propose the concept of the existence of a dynamic relay between Irs1 and Irs2 in hepatic insulin signaling during fasting and feeding. |
| 5031 | 18590692 | Here, we show that hepatic Irs1 and Irs2 function in a distinct manner in the regulation of glucose homeostasis. |
| 5032 | 18590692 | The PI3K activity associated with Irs2 began to increase during fasting, reached its peak immediately after refeeding, and decreased rapidly thereafter. |
| 5033 | 18590692 | By contrast, the PI3K activity associated with Irs1 began to increase a few hours after refeeding and reached its peak thereafter. |
| 5034 | 18590692 | The data indicate that Irs2 mainly functions during fasting and immediately after refeeding, and Irs1 functions primarily after refeeding. |
| 5035 | 18590692 | In fact, liver-specific Irs1-knockout mice failed to exhibit insulin resistance during fasting, but showed insulin resistance after refeeding; conversely, liver-specific Irs2-knockout mice displayed insulin resistance during fasting but not after refeeding. |
| 5036 | 18590692 | We propose the concept of the existence of a dynamic relay between Irs1 and Irs2 in hepatic insulin signaling during fasting and feeding. |
| 5037 | 18590693 | Inactivation of hepatic Foxo1 by insulin signaling is required for adaptive nutrient homeostasis and endocrine growth regulation. |
| 5038 | 18590693 | To assess the contribution of Foxo1 to metabolic dysregulation during hepatic insulin resistance, we disrupted Foxo1 expression in the liver of mice lacking hepatic Irs1 and Irs2 (DKO mice). |
| 5039 | 18590693 | DKO mice were small and developed diabetes; analysis of the DKO-liver transcriptome identified perturbed expression of growth and metabolic genes, including increased Ppargc1a and Igfbp1, and decreased glucokinase, Srebp1c, Ghr, and Igf1. |
| 5040 | 18590693 | Liver-specific deletion of Foxo1 in DKO mice resulted in significant normalization of the DKO-liver transcriptome and partial restoration of the response to fasting and feeding, near normal blood glucose and insulin concentrations, and normalization of body size. |
| 5041 | 18590693 | These results demonstrate that constitutively active Foxo1 significantly contributes to hyperglycemia during severe hepatic insulin resistance, and that the Irs1/2 --> PI3K --> Akt --> Foxo1 branch of insulin signaling is largely responsible for hepatic insulin-regulated glucose homeostasis and somatic growth. |
| 5042 | 18598780 | Upstream of mTOR key signalling molecules are the small GTPase Ras, the lipid kinase PI3K, the Akt kinase, and the GTPase Rheb, which are known to be deregulated in many human cancers. |
| 5043 | 18598780 | Mutations in the mTOR pathway component genes TSC1, TSC2, LKB1, PTEN, VHL, NF1 and PKD1 trigger the development of the syndromes tuberous sclerosis, Peutz-Jeghers syndrome, Cowden syndrome, Bannayan-Riley-Ruvalcaba syndrome, Lhermitte-Duclos disease, Proteus syndrome, von Hippel-Lindau disease, Neurofibromatosis type 1, and Polycystic kidney disease, respectively. |
| 5044 | 18641049 | Akt kinase (Akt) is an important molecule in insulin signaling, implicated in regulation of glucose uptake, cell growth, cell survival, protein synthesis, and endothelial nitric oxide (NO) production. |
| 5045 | 18641049 | Impaired Akt activation in insulin-sensitive tissues contributes to IR. |
| 5046 | 18641049 | We also studied expression and phosphorylation of the mammalian target of rapamycin (mTOR) and endothelial NO synthase (eNOS), molecules downstream of Akt in the insulin signaling cascade, and documented modulators of renal injury. |
| 5047 | 18641049 | Acute PI3K inhibition with wortmannin (100 mug/kg) attenuated renal Akt and mTOR activities in ZO, but not in ZL rats. |
| 5048 | 18653476 | Notably, both are inhibited by wortmannin and LY294002 and signal through phosphatidylinositol-3-kinase (PI3K)-dependent kinases SGK1 and Akt. |
| 5049 | 18653476 | We have found that ENaC-dependent Na(+) transport was blocked by inhibitors of the p110-alpha isoform of PI3K, but not by inhibitors of p110-beta, -gamma, or -delta. |
| 5050 | 18653476 | Inhibitors that block Na(+) current also blocked SGK1 and Akt phosphorylation. |
| 5051 | 18653476 | In contrast to insulin-stimulated glucose uptake in muscle cells, p110-beta inhibition did not enhance sensitivity to p110-alpha inhibition. |
| 5052 | 18653476 | These data support the conclusion that ENaC-dependent Na(+) current is controlled exclusively by p110-alpha, the same isoform that is the principal mediator of insulin effects on glucose metabolism, and lacks any dependence on p110-beta. |
| 5053 | 18653476 | Notably, both are inhibited by wortmannin and LY294002 and signal through phosphatidylinositol-3-kinase (PI3K)-dependent kinases SGK1 and Akt. |
| 5054 | 18653476 | We have found that ENaC-dependent Na(+) transport was blocked by inhibitors of the p110-alpha isoform of PI3K, but not by inhibitors of p110-beta, -gamma, or -delta. |
| 5055 | 18653476 | Inhibitors that block Na(+) current also blocked SGK1 and Akt phosphorylation. |
| 5056 | 18653476 | In contrast to insulin-stimulated glucose uptake in muscle cells, p110-beta inhibition did not enhance sensitivity to p110-alpha inhibition. |
| 5057 | 18653476 | These data support the conclusion that ENaC-dependent Na(+) current is controlled exclusively by p110-alpha, the same isoform that is the principal mediator of insulin effects on glucose metabolism, and lacks any dependence on p110-beta. |
| 5058 | 18653476 | Notably, both are inhibited by wortmannin and LY294002 and signal through phosphatidylinositol-3-kinase (PI3K)-dependent kinases SGK1 and Akt. |
| 5059 | 18653476 | We have found that ENaC-dependent Na(+) transport was blocked by inhibitors of the p110-alpha isoform of PI3K, but not by inhibitors of p110-beta, -gamma, or -delta. |
| 5060 | 18653476 | Inhibitors that block Na(+) current also blocked SGK1 and Akt phosphorylation. |
| 5061 | 18653476 | In contrast to insulin-stimulated glucose uptake in muscle cells, p110-beta inhibition did not enhance sensitivity to p110-alpha inhibition. |
| 5062 | 18653476 | These data support the conclusion that ENaC-dependent Na(+) current is controlled exclusively by p110-alpha, the same isoform that is the principal mediator of insulin effects on glucose metabolism, and lacks any dependence on p110-beta. |
| 5063 | 18653476 | Notably, both are inhibited by wortmannin and LY294002 and signal through phosphatidylinositol-3-kinase (PI3K)-dependent kinases SGK1 and Akt. |
| 5064 | 18653476 | We have found that ENaC-dependent Na(+) transport was blocked by inhibitors of the p110-alpha isoform of PI3K, but not by inhibitors of p110-beta, -gamma, or -delta. |
| 5065 | 18653476 | Inhibitors that block Na(+) current also blocked SGK1 and Akt phosphorylation. |
| 5066 | 18653476 | In contrast to insulin-stimulated glucose uptake in muscle cells, p110-beta inhibition did not enhance sensitivity to p110-alpha inhibition. |
| 5067 | 18653476 | These data support the conclusion that ENaC-dependent Na(+) current is controlled exclusively by p110-alpha, the same isoform that is the principal mediator of insulin effects on glucose metabolism, and lacks any dependence on p110-beta. |
| 5068 | 18673414 | Mutations in the arginine vasopressin (AVP)-neurophysin II (NP-II) gene that affect the folding and transport of the prohormone result in loss of secretion of the anti-diuretic hormone AVP from pituitary nerve terminals and cause autosomal dominant familial neurohypophyseal diabetes insipidus (adFNDI). |
| 5069 | 18673414 | This was shown by the expression of a Vps34 dominant negative, which down-regulates the PI3k class III-dependent signalling needed for autophagosome (APH) formation, by genetic silencing as a result of RNA interference (RNAi) of Lamp2, a protein indispensable for the fusion of APHs with lysosomes, and by RNAi silencing of the lysosomal protease CD. |
| 5070 | 18818290 | Insulin regulates glucagon-like peptide-1 secretion from the enteroendocrine L cell. |
| 5071 | 18818290 | Insulin resistance and type 2 diabetes mellitus are associated with impaired postprandial secretion of glucagon-like peptide-1 (GLP-1), a potent insulinotropic hormone. |
| 5072 | 18818290 | We therefore hypothesized that the L cell is responsive to insulin and that insulin resistance impairs GLP-1 secretion. |
| 5073 | 18818290 | In all cells, insulin activated the phosphatidylinositol 3 kinase-Akt and MAPK kinase (MEK)-ERK1/2 pathways and stimulated GLP-1 secretion by up to 275 +/- 58%. |
| 5074 | 18818290 | Insulin resistance was induced by 24 h pretreatment with 10(-7) m insulin, causing a marked reduction in activation of Akt and ERK1/2. |
| 5075 | 18818290 | Furthermore, both insulin-induced GLP-1 release and secretion in response to glucose-dependent insulinotropic peptide and phorbol-12-myristate-13-acetate were significantly attenuated. |
| 5076 | 18818290 | Whereas inhibition of phosphatidylinositol 3 kinase with LY294002 potentiated insulin-induced GLP-1 release, secretion was abrogated by inhibiting the MEK-ERK1/2 pathway with PD98059 or by overexpression of a kinase-dead MEK1-ERK2 fusion protein. |
| 5077 | 18818290 | These findings indicate that the intestinal L cell is responsive to insulin and that insulin resistance in vitro and in vivo is associated with impaired GLP-1 secretion. |
| 5078 | 18818290 | Insulin regulates glucagon-like peptide-1 secretion from the enteroendocrine L cell. |
| 5079 | 18818290 | Insulin resistance and type 2 diabetes mellitus are associated with impaired postprandial secretion of glucagon-like peptide-1 (GLP-1), a potent insulinotropic hormone. |
| 5080 | 18818290 | We therefore hypothesized that the L cell is responsive to insulin and that insulin resistance impairs GLP-1 secretion. |
| 5081 | 18818290 | In all cells, insulin activated the phosphatidylinositol 3 kinase-Akt and MAPK kinase (MEK)-ERK1/2 pathways and stimulated GLP-1 secretion by up to 275 +/- 58%. |
| 5082 | 18818290 | Insulin resistance was induced by 24 h pretreatment with 10(-7) m insulin, causing a marked reduction in activation of Akt and ERK1/2. |
| 5083 | 18818290 | Furthermore, both insulin-induced GLP-1 release and secretion in response to glucose-dependent insulinotropic peptide and phorbol-12-myristate-13-acetate were significantly attenuated. |
| 5084 | 18818290 | Whereas inhibition of phosphatidylinositol 3 kinase with LY294002 potentiated insulin-induced GLP-1 release, secretion was abrogated by inhibiting the MEK-ERK1/2 pathway with PD98059 or by overexpression of a kinase-dead MEK1-ERK2 fusion protein. |
| 5085 | 18818290 | These findings indicate that the intestinal L cell is responsive to insulin and that insulin resistance in vitro and in vivo is associated with impaired GLP-1 secretion. |
| 5086 | 18832180 | Consistent with these findings are the observations that boss mutants had reduced PI3K activity and phospho-AKT levels, which indicates that BOSS is required for proper insulin signaling. |
| 5087 | 18846471 | Co-incubation with insulin had no additional effect, but the cellular uptake was decreased by wortmannin and SB 203580, specific inhibitors of phosphatidylinositol 3-kinase (PI3K) and p38 mitogen-activated protein kinase (p38 MAPK), respectively. |
| 5088 | 18846471 | It is concluded that the increased glucose transport activity of M. speciosa is associated with increases in activities of the key enzymes dependent to the insulin-stimulated glucose transport for its acute action, and increases in the GLUT1 content for its long-term effect. |
| 5089 | 18922796 | Stimulatory effects of insulin-like growth factor-I on growth plate chondrogenesis are mediated by nuclear factor-kappaB p65. |
| 5090 | 18922796 | Insulin-like growth factor-I (IGF-I) is an important regulator of endochondral ossification. |
| 5091 | 18922796 | In this study, we first cultured rat metatarsal bones with IGF-I and/or pyrrolidine dithiocarbamate (PDTC), a known NF-kappaB inhibitor. |
| 5092 | 18922796 | Moreover, the inhibition of the phosphatidylinositol 3-kinase and Akt abolished the effects of IGF-I on NF-kappaB activation. |
| 5093 | 18923314 | Insulin potentiates the proliferation and bone morphogenetic protein-2-induced osteogenic differentiation of rat spinal ligament cells via extracellular signal-regulated kinase and phosphatidylinositol 3-kinase. |
| 5094 | 18945941 | High glucose promotes retinal endothelial cell migration through activation of Src, PI3K/Akt1/eNOS, and ERKs. |
| 5095 | 18945941 | Retinal EC under high-glucose conditions also expressed increased levels of fibronectin, osteopontin, and alpha(v)beta(3)-integrin, and reduced levels of thrombospondin-1. |
| 5096 | 18945941 | These changes were concomitant with sustained activation of the downstream prosurvival and promigratory signaling pathways, including Src kinase, phosphatidylinositol 3-kinase/Akt1/endothelial nitric oxide synthase, and ERKs. |
| 5097 | 18945941 | High glucose promotes retinal endothelial cell migration through activation of Src, PI3K/Akt1/eNOS, and ERKs. |
| 5098 | 18945941 | Retinal EC under high-glucose conditions also expressed increased levels of fibronectin, osteopontin, and alpha(v)beta(3)-integrin, and reduced levels of thrombospondin-1. |
| 5099 | 18945941 | These changes were concomitant with sustained activation of the downstream prosurvival and promigratory signaling pathways, including Src kinase, phosphatidylinositol 3-kinase/Akt1/endothelial nitric oxide synthase, and ERKs. |
| 5100 | 18972094 | Combined thiazolidinedione-metformin treatment synergistically improves insulin signalling to insulin receptor substrate-1-dependent phosphatidylinositol 3-kinase, atypical protein kinase C and protein kinase B/Akt in human diabetic muscle. |
| 5101 | 19020099 | Leptin-enhanced neointimal hyperplasia is reduced by mTOR and PI3K inhibitors. |
| 5102 | 19020099 | Here we show that leptin activates the mammalian target of rapamycin (mTOR) signaling pathway in primary murine vascular smooth muscle cells (VSMC) and stimulates VSMC proliferation in a PI3K-dependent fashion. |
| 5103 | 19020099 | Combination therapy with LY294002, a PI3K inhibitor, and sirolimus effectively inhibits leptin-enhanced neointimal hyperplasia. |
| 5104 | 19020099 | Leptin-enhanced neointimal hyperplasia is reduced by mTOR and PI3K inhibitors. |
| 5105 | 19020099 | Here we show that leptin activates the mammalian target of rapamycin (mTOR) signaling pathway in primary murine vascular smooth muscle cells (VSMC) and stimulates VSMC proliferation in a PI3K-dependent fashion. |
| 5106 | 19020099 | Combination therapy with LY294002, a PI3K inhibitor, and sirolimus effectively inhibits leptin-enhanced neointimal hyperplasia. |
| 5107 | 19020099 | Leptin-enhanced neointimal hyperplasia is reduced by mTOR and PI3K inhibitors. |
| 5108 | 19020099 | Here we show that leptin activates the mammalian target of rapamycin (mTOR) signaling pathway in primary murine vascular smooth muscle cells (VSMC) and stimulates VSMC proliferation in a PI3K-dependent fashion. |
| 5109 | 19020099 | Combination therapy with LY294002, a PI3K inhibitor, and sirolimus effectively inhibits leptin-enhanced neointimal hyperplasia. |
| 5110 | 19035854 | In the present study, we stably co-expressed c-Myc and eGFP [enhanced GFP (green fluorescent protein)] dual-tagged recombinant GLUT4 with recombinant IRS1 (insulin receptor substrate 1) in HEK-293 cells (human embryonic kidney cells) (HEK-293.IRS1.GLUT4 cells). |
| 5111 | 19035854 | TRF assays confirmed insulin-stimulated GLUT4 translocation, which can be inhibited by PI3K (phosphoinositide 3-kinase) or Akt [also called PKB (protein kinase B)] inhibitors. |
| 5112 | 19035854 | Treatment with palmitate increased IRS1 serine phosphorylation and reduced insulin-stimulated Akt phosphorylation and GLUT4 translocation, indicating insulin resistance. |
| 5113 | 19035854 | Knockdown of PTEN (phosphatase and tensin homologue deleted on chromosome 10) and PTP1B (protein tyrosine phosphatase 1B) gene expression by siRNA (small interfering RNA) treatment significantly increased GLUT4 translocation only in cells treated with palmitate but not in untreated cells. |
| 5114 | 19035854 | Similar results were obtained on treatment with siRNA of JNK1 (c-Jun N-terminal kinase 1), S6K1 (ribosomal protein S6 kinase, 70 kDa, polypeptide 1) and PKC(theta) (protein kinase C theta). |
| 5115 | 19043794 | As such, this study measured insulin receptor substrate-1 (IRS-1), insulin receptor substrate-2 (IRS-2), and phosphatidylinositol 3-kinase (PI3-K) P-85alpha mRNA expression levels in classical insulin-responsive sensitive tissues (liver, skeletal muscle, and abdominal fat) and peripheral leukocytes between cats and dogs by qRT-PCR. |
| 5116 | 19043794 | In addition, enzymes involved in glucose and lipid metabolism, malate dehydrogenase (MDH), glucose-6-phosphate dehydrogenase (G6PDH) and fatty acid synthase (FAS) were also assessed since glucose and lipid metabolism differs between cats and dogs. |
| 5117 | 19043794 | Overall, IRS-1, IRS-2, PI3-K, MDH, G6DPH, and FAS mRNA tissue expression profiles demonstrated different levels of expression, in various tissues for both canines and felines, which was expected. |
| 5118 | 19043794 | In addition, IRS-1, IRS-2, PI3-K, MDH, G6DPH, and FAS mRNA expression was significantly higher in canine versus feline tissues, including peripheral leukocytes. |
| 5119 | 19043794 | Remarkable differences in insulin signaling gene expression between felines and canines indicate that cats may have an underlying low insulin sensitivity level due to low IRS-1, IRS-2, and PI3-K P-85alpha mRNA expression levels which would predispose cats to develop insulin resistance. |
| 5120 | 19043794 | Moreover, differences in glucose and lipid metabolism related gene expression (MDH, G6DPH, and FAS) demonstrate that felines have an overall lower metabolic rate in various tissues which may be attributed to overall lower insulin signaling gene expression and a lack of physical activity as compared to canines. |
| 5121 | 19043794 | As such, this study measured insulin receptor substrate-1 (IRS-1), insulin receptor substrate-2 (IRS-2), and phosphatidylinositol 3-kinase (PI3-K) P-85alpha mRNA expression levels in classical insulin-responsive sensitive tissues (liver, skeletal muscle, and abdominal fat) and peripheral leukocytes between cats and dogs by qRT-PCR. |
| 5122 | 19043794 | In addition, enzymes involved in glucose and lipid metabolism, malate dehydrogenase (MDH), glucose-6-phosphate dehydrogenase (G6PDH) and fatty acid synthase (FAS) were also assessed since glucose and lipid metabolism differs between cats and dogs. |
| 5123 | 19043794 | Overall, IRS-1, IRS-2, PI3-K, MDH, G6DPH, and FAS mRNA tissue expression profiles demonstrated different levels of expression, in various tissues for both canines and felines, which was expected. |
| 5124 | 19043794 | In addition, IRS-1, IRS-2, PI3-K, MDH, G6DPH, and FAS mRNA expression was significantly higher in canine versus feline tissues, including peripheral leukocytes. |
| 5125 | 19043794 | Remarkable differences in insulin signaling gene expression between felines and canines indicate that cats may have an underlying low insulin sensitivity level due to low IRS-1, IRS-2, and PI3-K P-85alpha mRNA expression levels which would predispose cats to develop insulin resistance. |
| 5126 | 19043794 | Moreover, differences in glucose and lipid metabolism related gene expression (MDH, G6DPH, and FAS) demonstrate that felines have an overall lower metabolic rate in various tissues which may be attributed to overall lower insulin signaling gene expression and a lack of physical activity as compared to canines. |
| 5127 | 19043794 | As such, this study measured insulin receptor substrate-1 (IRS-1), insulin receptor substrate-2 (IRS-2), and phosphatidylinositol 3-kinase (PI3-K) P-85alpha mRNA expression levels in classical insulin-responsive sensitive tissues (liver, skeletal muscle, and abdominal fat) and peripheral leukocytes between cats and dogs by qRT-PCR. |
| 5128 | 19043794 | In addition, enzymes involved in glucose and lipid metabolism, malate dehydrogenase (MDH), glucose-6-phosphate dehydrogenase (G6PDH) and fatty acid synthase (FAS) were also assessed since glucose and lipid metabolism differs between cats and dogs. |
| 5129 | 19043794 | Overall, IRS-1, IRS-2, PI3-K, MDH, G6DPH, and FAS mRNA tissue expression profiles demonstrated different levels of expression, in various tissues for both canines and felines, which was expected. |
| 5130 | 19043794 | In addition, IRS-1, IRS-2, PI3-K, MDH, G6DPH, and FAS mRNA expression was significantly higher in canine versus feline tissues, including peripheral leukocytes. |
| 5131 | 19043794 | Remarkable differences in insulin signaling gene expression between felines and canines indicate that cats may have an underlying low insulin sensitivity level due to low IRS-1, IRS-2, and PI3-K P-85alpha mRNA expression levels which would predispose cats to develop insulin resistance. |
| 5132 | 19043794 | Moreover, differences in glucose and lipid metabolism related gene expression (MDH, G6DPH, and FAS) demonstrate that felines have an overall lower metabolic rate in various tissues which may be attributed to overall lower insulin signaling gene expression and a lack of physical activity as compared to canines. |
| 5133 | 19043794 | As such, this study measured insulin receptor substrate-1 (IRS-1), insulin receptor substrate-2 (IRS-2), and phosphatidylinositol 3-kinase (PI3-K) P-85alpha mRNA expression levels in classical insulin-responsive sensitive tissues (liver, skeletal muscle, and abdominal fat) and peripheral leukocytes between cats and dogs by qRT-PCR. |
| 5134 | 19043794 | In addition, enzymes involved in glucose and lipid metabolism, malate dehydrogenase (MDH), glucose-6-phosphate dehydrogenase (G6PDH) and fatty acid synthase (FAS) were also assessed since glucose and lipid metabolism differs between cats and dogs. |
| 5135 | 19043794 | Overall, IRS-1, IRS-2, PI3-K, MDH, G6DPH, and FAS mRNA tissue expression profiles demonstrated different levels of expression, in various tissues for both canines and felines, which was expected. |
| 5136 | 19043794 | In addition, IRS-1, IRS-2, PI3-K, MDH, G6DPH, and FAS mRNA expression was significantly higher in canine versus feline tissues, including peripheral leukocytes. |
| 5137 | 19043794 | Remarkable differences in insulin signaling gene expression between felines and canines indicate that cats may have an underlying low insulin sensitivity level due to low IRS-1, IRS-2, and PI3-K P-85alpha mRNA expression levels which would predispose cats to develop insulin resistance. |
| 5138 | 19043794 | Moreover, differences in glucose and lipid metabolism related gene expression (MDH, G6DPH, and FAS) demonstrate that felines have an overall lower metabolic rate in various tissues which may be attributed to overall lower insulin signaling gene expression and a lack of physical activity as compared to canines. |
| 5139 | 19049803 | Insulin regulates P-glycoprotein in rat brain microvessel endothelial cells via an insulin receptor-mediated PKC/NF-kappaB pathway but not a PI3K/Akt pathway. |
| 5140 | 19049803 | This induced effect was blocked by insulin receptor antibody, insulin receptor tyrosine kinase inhibitor I-OMe-AG538, PKC inhibitor chelerythrine and NF-kappaB inhibitor pyrrolidine dithiocarbamate ammonium (PDTC). |
| 5141 | 19049803 | But this induced effect was not inhibited by phosphatidylinositol 3-kinase (PI3K)/Akt inhibitor LY294002. |
| 5142 | 19049803 | These results indicated that insulin regulated P-glycoprotein function and expression through signal transduction pathways involving activation of PKC/NF-kappaB but not PI3K/Akt pathway. |
| 5143 | 19049803 | Insulin regulates P-glycoprotein in rat brain microvessel endothelial cells via an insulin receptor-mediated PKC/NF-kappaB pathway but not a PI3K/Akt pathway. |
| 5144 | 19049803 | This induced effect was blocked by insulin receptor antibody, insulin receptor tyrosine kinase inhibitor I-OMe-AG538, PKC inhibitor chelerythrine and NF-kappaB inhibitor pyrrolidine dithiocarbamate ammonium (PDTC). |
| 5145 | 19049803 | But this induced effect was not inhibited by phosphatidylinositol 3-kinase (PI3K)/Akt inhibitor LY294002. |
| 5146 | 19049803 | These results indicated that insulin regulated P-glycoprotein function and expression through signal transduction pathways involving activation of PKC/NF-kappaB but not PI3K/Akt pathway. |
| 5147 | 19049803 | Insulin regulates P-glycoprotein in rat brain microvessel endothelial cells via an insulin receptor-mediated PKC/NF-kappaB pathway but not a PI3K/Akt pathway. |
| 5148 | 19049803 | This induced effect was blocked by insulin receptor antibody, insulin receptor tyrosine kinase inhibitor I-OMe-AG538, PKC inhibitor chelerythrine and NF-kappaB inhibitor pyrrolidine dithiocarbamate ammonium (PDTC). |
| 5149 | 19049803 | But this induced effect was not inhibited by phosphatidylinositol 3-kinase (PI3K)/Akt inhibitor LY294002. |
| 5150 | 19049803 | These results indicated that insulin regulated P-glycoprotein function and expression through signal transduction pathways involving activation of PKC/NF-kappaB but not PI3K/Akt pathway. |
| 5151 | 19052259 | BLX-1002, a novel thiazolidinedione with no PPAR affinity, stimulates AMP-activated protein kinase activity, raises cytosolic Ca2+, and enhances glucose-stimulated insulin secretion in a PI3K-dependent manner. |
| 5152 | 19052259 | The stimulatory effect of BLX-1002 on insulin secretion at high glucose was completely abolished by treatment with the phosphatidylinositol 3-kinase (PI3K) inhibitors wortmannin or LY-294002. |
| 5153 | 19052259 | Our study suggests that BLX-1002 potentiates insulin secretion only at high glucose in beta-cells in a PI3K-dependent manner. |
| 5154 | 19052259 | BLX-1002, a novel thiazolidinedione with no PPAR affinity, stimulates AMP-activated protein kinase activity, raises cytosolic Ca2+, and enhances glucose-stimulated insulin secretion in a PI3K-dependent manner. |
| 5155 | 19052259 | The stimulatory effect of BLX-1002 on insulin secretion at high glucose was completely abolished by treatment with the phosphatidylinositol 3-kinase (PI3K) inhibitors wortmannin or LY-294002. |
| 5156 | 19052259 | Our study suggests that BLX-1002 potentiates insulin secretion only at high glucose in beta-cells in a PI3K-dependent manner. |
| 5157 | 19052259 | BLX-1002, a novel thiazolidinedione with no PPAR affinity, stimulates AMP-activated protein kinase activity, raises cytosolic Ca2+, and enhances glucose-stimulated insulin secretion in a PI3K-dependent manner. |
| 5158 | 19052259 | The stimulatory effect of BLX-1002 on insulin secretion at high glucose was completely abolished by treatment with the phosphatidylinositol 3-kinase (PI3K) inhibitors wortmannin or LY-294002. |
| 5159 | 19052259 | Our study suggests that BLX-1002 potentiates insulin secretion only at high glucose in beta-cells in a PI3K-dependent manner. |
| 5160 | 19065826 | [Adenylyl cyclase signaling mechanisms of the insulin superfamily peptide action and their impairment in myometrium of pregnant women with type 2 diabetes]. |
| 5161 | 19065826 | For the first time we found in myometrium of the women and pregnant women that adenylyl cyclase (AC) stimulating effects of relaxin, insulin and insulin growth factor 1 are realized via six-component AC signaling mechanisms involving the following signaling chain: receptor-tyrosine kinase ==> Gi protein (beta gamma dimmer) ==> phosphatidylinositol 3-kinase ==> protein kinase C (zeta) ==> Gs protein ==> adenylyl cyclase (AC), which are similar to the discovered adenylyl cyclase signaling mechanisms of insulin and relaxin action in vertebrates (rat) and invertebrates (mollusk). |
| 5162 | 19065826 | The effect of relaxin is more pronounced as compared with other peptides (relaxin > insulin > insulin-like growth factor-1) in myometrium of pregnant women. |
| 5163 | 19065826 | For the first time we revealed the functional defects in distal parts of adenylyl cyclase signaling mechanisms of the insulin superfamily peptides action in the condition type-2 diabetes (the increase of the basal adenylyl cyclase activity and decrease of the peptide-stimulated AX activity in presence of guanilylimidodiphosphate). |
| 5164 | 19070612 | The effect of compound 1 on glucose uptake was completely nullified by wortmannin, an inhibitor of phosphatidylinositol 3-kinase (PI3K), RO318220, an inhibitor of protein kinase C (PKC), PD98059, a specific inhibitor of mitogen-activated protein kinase (MEK), cycloheximide, an inhibitor of protein synthesis, and colchicine, a microtubule-depolymerizing agent. |
| 5165 | 19106089 | Recently, we identified that the death effector domain-containing DEDD impedes mitotic progression by inhibiting Cdk1 (cyclin-dependent kinase 1) and thus maintains an increase of cell size during the mitotic phase. |
| 5166 | 19106089 | Here we found that DEDD also associates with S6 kinase 1 (S6K1), downstream of phosphatidylinositol 3-kinase, and supports its activity by preventing inhibitory phosphorylation of S6K1 brought about by Cdk1 during the mitotic phase. |
| 5167 | 19121967 | Quantitative PCR (qPCR) confirmed the differential expression of genes including glycerol kinase (Gyk), phosphatidylinositol 3-kinase regulatory subunit, polypeptide 1 (p85 alpha) (Pik3r1), insulin-like growth factor 1 (Igf1), and growth factor receptor bound protein 2-associated protein 1 (Gab1). |
| 5168 | 19121967 | Network component analysis demonstrated that transcription factor activities of myogenic differentiation 1 (MYOD), myogenic regulatory factor 5 (MYF5), myogenin (MYOG), nuclear receptor subfamily 4, group A, member 1 (NUR77) are decreased in the Gyk KO whereas the activity of paired box 3 (PAX3) is increased. |
| 5169 | 19139117 | Peroxisome proliferator-activated receptor gamma agonist pioglitazone prevents the hyperglycemia caused by phosphatidylinositol 3-kinase pathway inhibition by PX-866 without affecting antitumor activity. |
| 5170 | 19139117 | The phosphatidylinositol 3-kinase (PI3K)/Akt signaling cascade is an important component of the insulin signaling in normal tissues leading to glucose uptake and homeostasis and for cell survival signaling in cancer cells. |
| 5171 | 19139117 | Hyperglycemia is an on-target side effect of many inhibitors of PI3K/Akt signaling including the specific PI3K inhibitor PX-866. |
| 5172 | 19139117 | Thus, peroxisome proliferator-activated receptor gamma agonists may be useful in overcoming the increase in blood glucose caused by inhibitors of PI3K signaling by preventing the inhibition of normal tissue insulin-mediated glucose uptake without affecting antitumor activity. |
| 5173 | 19139117 | Peroxisome proliferator-activated receptor gamma agonist pioglitazone prevents the hyperglycemia caused by phosphatidylinositol 3-kinase pathway inhibition by PX-866 without affecting antitumor activity. |
| 5174 | 19139117 | The phosphatidylinositol 3-kinase (PI3K)/Akt signaling cascade is an important component of the insulin signaling in normal tissues leading to glucose uptake and homeostasis and for cell survival signaling in cancer cells. |
| 5175 | 19139117 | Hyperglycemia is an on-target side effect of many inhibitors of PI3K/Akt signaling including the specific PI3K inhibitor PX-866. |
| 5176 | 19139117 | Thus, peroxisome proliferator-activated receptor gamma agonists may be useful in overcoming the increase in blood glucose caused by inhibitors of PI3K signaling by preventing the inhibition of normal tissue insulin-mediated glucose uptake without affecting antitumor activity. |
| 5177 | 19139117 | Peroxisome proliferator-activated receptor gamma agonist pioglitazone prevents the hyperglycemia caused by phosphatidylinositol 3-kinase pathway inhibition by PX-866 without affecting antitumor activity. |
| 5178 | 19139117 | The phosphatidylinositol 3-kinase (PI3K)/Akt signaling cascade is an important component of the insulin signaling in normal tissues leading to glucose uptake and homeostasis and for cell survival signaling in cancer cells. |
| 5179 | 19139117 | Hyperglycemia is an on-target side effect of many inhibitors of PI3K/Akt signaling including the specific PI3K inhibitor PX-866. |
| 5180 | 19139117 | Thus, peroxisome proliferator-activated receptor gamma agonists may be useful in overcoming the increase in blood glucose caused by inhibitors of PI3K signaling by preventing the inhibition of normal tissue insulin-mediated glucose uptake without affecting antitumor activity. |
| 5181 | 19139117 | Peroxisome proliferator-activated receptor gamma agonist pioglitazone prevents the hyperglycemia caused by phosphatidylinositol 3-kinase pathway inhibition by PX-866 without affecting antitumor activity. |
| 5182 | 19139117 | The phosphatidylinositol 3-kinase (PI3K)/Akt signaling cascade is an important component of the insulin signaling in normal tissues leading to glucose uptake and homeostasis and for cell survival signaling in cancer cells. |
| 5183 | 19139117 | Hyperglycemia is an on-target side effect of many inhibitors of PI3K/Akt signaling including the specific PI3K inhibitor PX-866. |
| 5184 | 19139117 | Thus, peroxisome proliferator-activated receptor gamma agonists may be useful in overcoming the increase in blood glucose caused by inhibitors of PI3K signaling by preventing the inhibition of normal tissue insulin-mediated glucose uptake without affecting antitumor activity. |
| 5185 | 19151258 | PPAR-alpha activation protects the type 2 diabetic myocardium against ischemia-reperfusion injury: involvement of the PI3-Kinase/Akt and NO pathway. |
| 5186 | 19151258 | We hypothesized that the activation of PPAR-alpha would exert cardioprotection in type 2 diabetic Goto-Kakizaki (GK) rats, involving mechanisms related to nitric oxide (NO) production via the phosphatidylinositol 3-kinase (PI3K)/Akt pathway. |
| 5187 | 19151258 | GK rats and age-matched Wistar rats (n >or= 7) were given either 1) the PPAR-alpha agonist WY-14643 (WY), 2) dimethyl sulfoxide (DMSO), 3) WY and the NO synthase inhibitor N(G)-nitro-l-arginine (l-NNA), 4) l-NNA, 5) WY and the PI3K inhibitor wortmannin, or 6) wortmannin alone intravenously before a 35-min period of coronary artery occlusion followed by 2 h of reperfusion. |
| 5188 | 19151258 | Infarct size (IS), expression of endothelial NO synthase (eNOS), inducible NO synthase, and Akt as well as nitrite/nitrate were determined. |
| 5189 | 19151258 | The results suggest that PPAR-alpha activation protects the type 2 diabetic rat myocardium against ischemia-reperfusion injury via the activation of the PI3K/Akt and NO pathway. |
| 5190 | 19151258 | PPAR-alpha activation protects the type 2 diabetic myocardium against ischemia-reperfusion injury: involvement of the PI3-Kinase/Akt and NO pathway. |
| 5191 | 19151258 | We hypothesized that the activation of PPAR-alpha would exert cardioprotection in type 2 diabetic Goto-Kakizaki (GK) rats, involving mechanisms related to nitric oxide (NO) production via the phosphatidylinositol 3-kinase (PI3K)/Akt pathway. |
| 5192 | 19151258 | GK rats and age-matched Wistar rats (n >or= 7) were given either 1) the PPAR-alpha agonist WY-14643 (WY), 2) dimethyl sulfoxide (DMSO), 3) WY and the NO synthase inhibitor N(G)-nitro-l-arginine (l-NNA), 4) l-NNA, 5) WY and the PI3K inhibitor wortmannin, or 6) wortmannin alone intravenously before a 35-min period of coronary artery occlusion followed by 2 h of reperfusion. |
| 5193 | 19151258 | Infarct size (IS), expression of endothelial NO synthase (eNOS), inducible NO synthase, and Akt as well as nitrite/nitrate were determined. |
| 5194 | 19151258 | The results suggest that PPAR-alpha activation protects the type 2 diabetic rat myocardium against ischemia-reperfusion injury via the activation of the PI3K/Akt and NO pathway. |
| 5195 | 19151258 | PPAR-alpha activation protects the type 2 diabetic myocardium against ischemia-reperfusion injury: involvement of the PI3-Kinase/Akt and NO pathway. |
| 5196 | 19151258 | We hypothesized that the activation of PPAR-alpha would exert cardioprotection in type 2 diabetic Goto-Kakizaki (GK) rats, involving mechanisms related to nitric oxide (NO) production via the phosphatidylinositol 3-kinase (PI3K)/Akt pathway. |
| 5197 | 19151258 | GK rats and age-matched Wistar rats (n >or= 7) were given either 1) the PPAR-alpha agonist WY-14643 (WY), 2) dimethyl sulfoxide (DMSO), 3) WY and the NO synthase inhibitor N(G)-nitro-l-arginine (l-NNA), 4) l-NNA, 5) WY and the PI3K inhibitor wortmannin, or 6) wortmannin alone intravenously before a 35-min period of coronary artery occlusion followed by 2 h of reperfusion. |
| 5198 | 19151258 | Infarct size (IS), expression of endothelial NO synthase (eNOS), inducible NO synthase, and Akt as well as nitrite/nitrate were determined. |
| 5199 | 19151258 | The results suggest that PPAR-alpha activation protects the type 2 diabetic rat myocardium against ischemia-reperfusion injury via the activation of the PI3K/Akt and NO pathway. |
| 5200 | 19188434 | High glucose suppresses epidermal growth factor receptor/phosphatidylinositol 3-kinase/Akt signaling pathway and attenuates corneal epithelial wound healing. |
| 5201 | 19190820 | Prolonged exposure to high insulin impairs the endothelial PI3-kinase/Akt/nitric oxide signalling. |
| 5202 | 19190820 | We therefore studied the consequences of prolonged insulin treatment of human umbilical vein endothelial cells (HUVEC) on the phosphatidylinositol-3'-kinase(PI3K)/Akt/nitric oxide(NO)-dependent insulin signaling, together with the expression of the pro-atherogenic molecule vascular cell adhesion molecule (VCAM)-1. |
| 5203 | 19190820 | In short-term incubations, insulin did not affect constitutive Akt and eNOS at any concentration, but significantly increased their active phosphorylated forms, and NO production. |
| 5204 | 19190820 | Such effects were accompanied by a boosting of insulin effect on VCAM-1 surface expression. |
| 5205 | 19190820 | In contrast, under similar conditions, insulin did not exert any significant effect on the surface expression of ICAM-1 and E-selectin. |
| 5206 | 19190820 | Therefore, prolonged exposure of HUVEC to high insulin levels induces a downregulation of the PI3K/Akt/eNOS axis. |
| 5207 | 19190820 | Prolonged exposure to high insulin impairs the endothelial PI3-kinase/Akt/nitric oxide signalling. |
| 5208 | 19190820 | We therefore studied the consequences of prolonged insulin treatment of human umbilical vein endothelial cells (HUVEC) on the phosphatidylinositol-3'-kinase(PI3K)/Akt/nitric oxide(NO)-dependent insulin signaling, together with the expression of the pro-atherogenic molecule vascular cell adhesion molecule (VCAM)-1. |
| 5209 | 19190820 | In short-term incubations, insulin did not affect constitutive Akt and eNOS at any concentration, but significantly increased their active phosphorylated forms, and NO production. |
| 5210 | 19190820 | Such effects were accompanied by a boosting of insulin effect on VCAM-1 surface expression. |
| 5211 | 19190820 | In contrast, under similar conditions, insulin did not exert any significant effect on the surface expression of ICAM-1 and E-selectin. |
| 5212 | 19190820 | Therefore, prolonged exposure of HUVEC to high insulin levels induces a downregulation of the PI3K/Akt/eNOS axis. |
| 5213 | 19221061 | In a previous study, cilostazol promoted differentiation of 3T3-L1 fibroblasts into adipocytes and improved insulin sensitivity by stimulating peroxisome proliferator-activated receptor (PPAR) gamma transcription. |
| 5214 | 19221061 | Elevated plasma insulin and resistin levels were significantly decreased by cilostazol, and decreased adiponectin mRNA expression was elevated along with increased plasma adiponectin. |
| 5215 | 19221061 | Cilostazol significantly increased both adipocyte fatty acid binding protein and fatty acid transport protein-1 mRNA expressions with increased glucose transport 4 in the adipose tissue. |
| 5216 | 19221061 | Cilostazol and rosiglitazone significantly suppressed proinflammatory markers (superoxide, tumor necrosis factor-alpha, and vascular cell adhesion molecule-1) in the carotid artery of db/db mice. |
| 5217 | 19221061 | The transcription activity stimulated by cilostazol was attenuated by KT5720 [(9R,10S,12S)-2,3,9,10,11,12-hexahydro-10-hydroxy-9-methyl-1-oxo-9, 12-epoxy-1H-diindolo[1,2,3-fg:3',2',1'-kl]pyrrolo [3,4-I][1,6]-benzodiazocine-10-carboxylic acid hexyl ester], a cAMP-dependent protein kinase inhibitor, and GW9662 (2-chloro-5-nitrobenzanilide), an antagonist of PPARgamma activity, indicative of implication of the phosphatidylinositol 3-kinase/Akt signal pathway. |
| 5218 | 19221061 | These results suggest that cilostazol may improve insulin sensitivity along with anti-inflammatory effects in type 2 diabetic patients via activation of both cAMP-dependent protein kinase and PPARgamma transcription. |
| 5219 | 19223652 | This change in the glucose sensitivity in the presence of insulin was reversed by the phosphatidylinositol 3-kinase (PI3K) inhibitor wortmannin (10 nM) but not by the mitogen-activated kinase (MAPK) inhibitor PD-98059 (PD; 50 microM). |
| 5220 | 19223652 | Finally, neither the AMPK inhibitor compound C nor the AMPK activator AICAR altered the activity of VMH GE neurons. |
| 5221 | 19223652 | These data suggest that insulin attenuates the ability of VMH GE neurons to sense decreased glucose via the PI3K signaling pathway. |
| 5222 | 19223652 | This change in the glucose sensitivity in the presence of insulin was reversed by the phosphatidylinositol 3-kinase (PI3K) inhibitor wortmannin (10 nM) but not by the mitogen-activated kinase (MAPK) inhibitor PD-98059 (PD; 50 microM). |
| 5223 | 19223652 | Finally, neither the AMPK inhibitor compound C nor the AMPK activator AICAR altered the activity of VMH GE neurons. |
| 5224 | 19223652 | These data suggest that insulin attenuates the ability of VMH GE neurons to sense decreased glucose via the PI3K signaling pathway. |
| 5225 | 19235132 | Insulin regulation of proliferation involves activation of AKT and ERK 1/2 signaling pathways in vascular smooth muscle cells. |
| 5226 | 19235132 | In this study, we investigated the role of protein kinase B (Akt) and p42/44 mitogen-activated protein kinase (ERK 1/2) signaling pathways in mediating the mitogenic action of INS in VSMCs. |
| 5227 | 19235132 | Incubation of rat VSMCs with INS (100 nM) for 10 min resulted in an increase of Akt phosphorylation by 6-fold (p<0.001) and ERK 1/2 phosphorylation by 3-fold (p<0.001). |
| 5228 | 19235132 | Pretreatment for 15 min with 10 muM of PI3K/Akt inhibitor LY294002 or with 20 muM PD98059, inhibitor of ERK 1/2, significantly reduced INS-stimulated Akt and ERK 1/2 phosphorylation by 76 and 75%, respectively. |
| 5229 | 19235132 | Prolonged treatment of VSMCs with INS for 24 h did not have an effect on either Akt or ERK1/2 phosphorylation. |
| 5230 | 19235132 | These results indicate that INS acts through Akt and ERK 1/2 signaling pathways to up-regulate proliferation of VSMC's. |
| 5231 | 19272022 | Growth factor or insulin stimulation induces a canonical cascade resulting in the transient phosphorylation of PtdIns(4,5)P(2) by PI3K (phosphoinositide 3-kinase) to form PtdIns(3,4,5)P(3), which is rapidly dephosphorylated either by PTEN (phosphatase and tensin homologue deleted on chromosome 10) back to PtdIns(4,5)P(2), or by the 5-ptases (inositol polyphosphate 5-phosphatases), generating PtdIns(3,4)P(2). |
| 5232 | 19272022 | Futhermore, the 5-ptases SHIP [SH2 (Src homology 2)-domain-containing inositol phosphatase] 2, SKIP (skeletal muscle- and kidney-enriched inositol phosphatase) and 72-5ptase (72 kDa 5-ptase)/Type IV/Inpp5e (inositol polyphosphate 5-phosphatase E) are implicated in negatively regulating insulin signalling and glucose homoeostasis in specific tissues. |
| 5233 | 19272022 | SHIP2 polymorphisms are associated with a predisposition to insulin resistance. |
| 5234 | 19272022 | In addition, 5-ptases such as SHIP1, SHIP2 and 72-5ptase/Type IV/Inpp5e regulate macrophage phagocytosis, and SHIP1 also controls haemopoietic cell proliferation. |
| 5235 | 19272793 | Ciliary neurotrophic factor (CNTF) signals through STAT3-SOCS3 pathway and protects rat pancreatic islets from cytokine-induced apoptosis. |
| 5236 | 19272793 | The medium contained, when necessary, specific inhibitors of the PI3K, MAPK and JAK/STAT3 pathways. mRNA expression (RT-PCR) and protein phosphorylation (Western blot) of Akt, ERK1/2 and STAT3, and SOCS-3 (RT-PCR and Western blot), as well as glucose-stimulated insulin secretion (GSIS) (Radioimmunoassay), were analyzed. |
| 5237 | 19272793 | Our results showed that Akt, ERK1 and STAT3 mRNA expression, as well as phosphorylated Akt and ERK1/2, was not affected by CNTF treatment. |
| 5238 | 19272793 | CNTF increased cytoplasmatic and nuclear phosphorylated STAT3, and the SOCS3 mRNA and protein expression. |
| 5239 | 19272793 | These effects were blocked by the JAK inhibitor, AG490 and by the STAT3 inhibitor Curcumin, but not by the MAPK inhibitor, PD98059, nor by the PI3K inhibitor, Wortmannin. |
| 5240 | 19272793 | In conclusion, CNTF signals through the JAK2/STAT3 cascade, increases SOCS3 expression, impairs GSIS and protects neonatal pancreatic rat islets from cytokine-induced apoptosis. |
| 5241 | 19272793 | Ciliary neurotrophic factor (CNTF) signals through STAT3-SOCS3 pathway and protects rat pancreatic islets from cytokine-induced apoptosis. |
| 5242 | 19272793 | The medium contained, when necessary, specific inhibitors of the PI3K, MAPK and JAK/STAT3 pathways. mRNA expression (RT-PCR) and protein phosphorylation (Western blot) of Akt, ERK1/2 and STAT3, and SOCS-3 (RT-PCR and Western blot), as well as glucose-stimulated insulin secretion (GSIS) (Radioimmunoassay), were analyzed. |
| 5243 | 19272793 | Our results showed that Akt, ERK1 and STAT3 mRNA expression, as well as phosphorylated Akt and ERK1/2, was not affected by CNTF treatment. |
| 5244 | 19272793 | CNTF increased cytoplasmatic and nuclear phosphorylated STAT3, and the SOCS3 mRNA and protein expression. |
| 5245 | 19272793 | These effects were blocked by the JAK inhibitor, AG490 and by the STAT3 inhibitor Curcumin, but not by the MAPK inhibitor, PD98059, nor by the PI3K inhibitor, Wortmannin. |
| 5246 | 19272793 | In conclusion, CNTF signals through the JAK2/STAT3 cascade, increases SOCS3 expression, impairs GSIS and protects neonatal pancreatic rat islets from cytokine-induced apoptosis. |
| 5247 | 19273608 | Insulin and insulin-like growth factor I (IGF-I) are ubiquitous hormones that regulate growth and metabolism of most mammalian cells, including pancreatic beta-cells. |
| 5248 | 19273608 | Insulin stimulation of betaIRKO and betaIRS2KO cells led to blunted activation of phosphatidylinositol 3-kinase and Akt kinase, while surprisingly, glucose failed to activate either kinase but phosphorylated extracellular signal-regulated kinase. |
| 5249 | 19276091 | Targeted disruption of ROCK1 causes insulin resistance in vivo. |
| 5250 | 19276091 | Rho-kinase (ROCK) isoforms have been shown to participate in insulin signaling and glucose metabolism in cultured cell lines. |
| 5251 | 19276091 | To investigate the physiological role of ROCK1 in the regulation of whole body glucose homeostasis and insulin sensitivity in vivo, we studied mice with global disruption of ROCK1. |
| 5252 | 19276091 | Interestingly, ROCK1 gene ablation caused a significant increase in glucose-induced insulin secretion, leading to hyperinsulinemia. |
| 5253 | 19276091 | To determine the mechanism(s) by which deletion of ROCK1 causes insulin resistance, we measured the ability of insulin to activate phosphatidylinositol 3-kinase and multiple distal pathways in skeletal muscle. |
| 5254 | 19276091 | Insulin-stimulated phosphatidylinositol 3-kinase activity associated with IRS-1 or phospho-tyrosine was also reduced approximately 40% without any alteration in tyrosine phosphorylation of insulin receptor in skeletal muscle. |
| 5255 | 19276091 | Insulin-induced phosphorylation of Akt, AS160, S6K, and S6 was also decreased in skeletal muscle. |
| 5256 | 19276091 | These data suggest that ROCK1 deficiency causes systemic insulin resistance by impairing insulin signaling in skeletal muscle. |
| 5257 | 19276091 | Thus, our results identify ROCK1 as a novel regulator of glucose homeostasis and insulin sensitivity in vivo, which could lead to new treatment approaches for obesity and type 2 diabetes. |
| 5258 | 19276091 | Targeted disruption of ROCK1 causes insulin resistance in vivo. |
| 5259 | 19276091 | Rho-kinase (ROCK) isoforms have been shown to participate in insulin signaling and glucose metabolism in cultured cell lines. |
| 5260 | 19276091 | To investigate the physiological role of ROCK1 in the regulation of whole body glucose homeostasis and insulin sensitivity in vivo, we studied mice with global disruption of ROCK1. |
| 5261 | 19276091 | Interestingly, ROCK1 gene ablation caused a significant increase in glucose-induced insulin secretion, leading to hyperinsulinemia. |
| 5262 | 19276091 | To determine the mechanism(s) by which deletion of ROCK1 causes insulin resistance, we measured the ability of insulin to activate phosphatidylinositol 3-kinase and multiple distal pathways in skeletal muscle. |
| 5263 | 19276091 | Insulin-stimulated phosphatidylinositol 3-kinase activity associated with IRS-1 or phospho-tyrosine was also reduced approximately 40% without any alteration in tyrosine phosphorylation of insulin receptor in skeletal muscle. |
| 5264 | 19276091 | Insulin-induced phosphorylation of Akt, AS160, S6K, and S6 was also decreased in skeletal muscle. |
| 5265 | 19276091 | These data suggest that ROCK1 deficiency causes systemic insulin resistance by impairing insulin signaling in skeletal muscle. |
| 5266 | 19276091 | Thus, our results identify ROCK1 as a novel regulator of glucose homeostasis and insulin sensitivity in vivo, which could lead to new treatment approaches for obesity and type 2 diabetes. |
| 5267 | 19330070 | Contribution of natural inhibitors to the understanding of the PI3K/PDK1/PKB pathway in the insulin-mediated intracellular signaling cascade. |
| 5268 | 19330070 | The critical initial steps in insulin action include phosphorylation of adapter proteins and activation of phosphatidylinositol 3-kinase (PI3K). |
| 5269 | 19330070 | The work of numerous different researchers indicates a role of PKB in regulating insulin-stimulated glucose uptake. |
| 5270 | 19330070 | The crucial role of lipid second messengers in PKB activation has been dissected through the use of the PI3K-specific inhibitors wortmannin and LY294002. |
| 5271 | 19330070 | Receptor-activated PI3K synthesizes the lipid second messenger PtdIns[3,4,5]-trisphosphate, leading to the recruitment of PKB to the membrane. |
| 5272 | 19330070 | Activation of PKB alpha is then achieved at the plasma membrane by phosphorylation of Thr308 in the activation-loop of the kinase domain and Ser473 in the carboxy-terminal regulatory region, respectively. 3-Phosphoinositide-dependent protein kinase-1 (PDK1) is responsible for T308 phosphorylation. |
| 5273 | 19330070 | The usage of specific inhibitors and natural compound has significantly contributed to investigate the molecular mechanism of PI3K/PDK1/PKB signaling pathway, leading to the putative therapeutics benefits of patients. |
| 5274 | 19330070 | This review focuses on the contribution of natural inhibitor or compound in our understanding of the mechanism by which insulin induces, especially in PI3K/PDK1/PKB signaling. |
| 5275 | 19330070 | Contribution of natural inhibitors to the understanding of the PI3K/PDK1/PKB pathway in the insulin-mediated intracellular signaling cascade. |
| 5276 | 19330070 | The critical initial steps in insulin action include phosphorylation of adapter proteins and activation of phosphatidylinositol 3-kinase (PI3K). |
| 5277 | 19330070 | The work of numerous different researchers indicates a role of PKB in regulating insulin-stimulated glucose uptake. |
| 5278 | 19330070 | The crucial role of lipid second messengers in PKB activation has been dissected through the use of the PI3K-specific inhibitors wortmannin and LY294002. |
| 5279 | 19330070 | Receptor-activated PI3K synthesizes the lipid second messenger PtdIns[3,4,5]-trisphosphate, leading to the recruitment of PKB to the membrane. |
| 5280 | 19330070 | Activation of PKB alpha is then achieved at the plasma membrane by phosphorylation of Thr308 in the activation-loop of the kinase domain and Ser473 in the carboxy-terminal regulatory region, respectively. 3-Phosphoinositide-dependent protein kinase-1 (PDK1) is responsible for T308 phosphorylation. |
| 5281 | 19330070 | The usage of specific inhibitors and natural compound has significantly contributed to investigate the molecular mechanism of PI3K/PDK1/PKB signaling pathway, leading to the putative therapeutics benefits of patients. |
| 5282 | 19330070 | This review focuses on the contribution of natural inhibitor or compound in our understanding of the mechanism by which insulin induces, especially in PI3K/PDK1/PKB signaling. |
| 5283 | 19330070 | Contribution of natural inhibitors to the understanding of the PI3K/PDK1/PKB pathway in the insulin-mediated intracellular signaling cascade. |
| 5284 | 19330070 | The critical initial steps in insulin action include phosphorylation of adapter proteins and activation of phosphatidylinositol 3-kinase (PI3K). |
| 5285 | 19330070 | The work of numerous different researchers indicates a role of PKB in regulating insulin-stimulated glucose uptake. |
| 5286 | 19330070 | The crucial role of lipid second messengers in PKB activation has been dissected through the use of the PI3K-specific inhibitors wortmannin and LY294002. |
| 5287 | 19330070 | Receptor-activated PI3K synthesizes the lipid second messenger PtdIns[3,4,5]-trisphosphate, leading to the recruitment of PKB to the membrane. |
| 5288 | 19330070 | Activation of PKB alpha is then achieved at the plasma membrane by phosphorylation of Thr308 in the activation-loop of the kinase domain and Ser473 in the carboxy-terminal regulatory region, respectively. 3-Phosphoinositide-dependent protein kinase-1 (PDK1) is responsible for T308 phosphorylation. |
| 5289 | 19330070 | The usage of specific inhibitors and natural compound has significantly contributed to investigate the molecular mechanism of PI3K/PDK1/PKB signaling pathway, leading to the putative therapeutics benefits of patients. |
| 5290 | 19330070 | This review focuses on the contribution of natural inhibitor or compound in our understanding of the mechanism by which insulin induces, especially in PI3K/PDK1/PKB signaling. |
| 5291 | 19330070 | Contribution of natural inhibitors to the understanding of the PI3K/PDK1/PKB pathway in the insulin-mediated intracellular signaling cascade. |
| 5292 | 19330070 | The critical initial steps in insulin action include phosphorylation of adapter proteins and activation of phosphatidylinositol 3-kinase (PI3K). |
| 5293 | 19330070 | The work of numerous different researchers indicates a role of PKB in regulating insulin-stimulated glucose uptake. |
| 5294 | 19330070 | The crucial role of lipid second messengers in PKB activation has been dissected through the use of the PI3K-specific inhibitors wortmannin and LY294002. |
| 5295 | 19330070 | Receptor-activated PI3K synthesizes the lipid second messenger PtdIns[3,4,5]-trisphosphate, leading to the recruitment of PKB to the membrane. |
| 5296 | 19330070 | Activation of PKB alpha is then achieved at the plasma membrane by phosphorylation of Thr308 in the activation-loop of the kinase domain and Ser473 in the carboxy-terminal regulatory region, respectively. 3-Phosphoinositide-dependent protein kinase-1 (PDK1) is responsible for T308 phosphorylation. |
| 5297 | 19330070 | The usage of specific inhibitors and natural compound has significantly contributed to investigate the molecular mechanism of PI3K/PDK1/PKB signaling pathway, leading to the putative therapeutics benefits of patients. |
| 5298 | 19330070 | This review focuses on the contribution of natural inhibitor or compound in our understanding of the mechanism by which insulin induces, especially in PI3K/PDK1/PKB signaling. |
| 5299 | 19330070 | Contribution of natural inhibitors to the understanding of the PI3K/PDK1/PKB pathway in the insulin-mediated intracellular signaling cascade. |
| 5300 | 19330070 | The critical initial steps in insulin action include phosphorylation of adapter proteins and activation of phosphatidylinositol 3-kinase (PI3K). |
| 5301 | 19330070 | The work of numerous different researchers indicates a role of PKB in regulating insulin-stimulated glucose uptake. |
| 5302 | 19330070 | The crucial role of lipid second messengers in PKB activation has been dissected through the use of the PI3K-specific inhibitors wortmannin and LY294002. |
| 5303 | 19330070 | Receptor-activated PI3K synthesizes the lipid second messenger PtdIns[3,4,5]-trisphosphate, leading to the recruitment of PKB to the membrane. |
| 5304 | 19330070 | Activation of PKB alpha is then achieved at the plasma membrane by phosphorylation of Thr308 in the activation-loop of the kinase domain and Ser473 in the carboxy-terminal regulatory region, respectively. 3-Phosphoinositide-dependent protein kinase-1 (PDK1) is responsible for T308 phosphorylation. |
| 5305 | 19330070 | The usage of specific inhibitors and natural compound has significantly contributed to investigate the molecular mechanism of PI3K/PDK1/PKB signaling pathway, leading to the putative therapeutics benefits of patients. |
| 5306 | 19330070 | This review focuses on the contribution of natural inhibitor or compound in our understanding of the mechanism by which insulin induces, especially in PI3K/PDK1/PKB signaling. |
| 5307 | 19330070 | Contribution of natural inhibitors to the understanding of the PI3K/PDK1/PKB pathway in the insulin-mediated intracellular signaling cascade. |
| 5308 | 19330070 | The critical initial steps in insulin action include phosphorylation of adapter proteins and activation of phosphatidylinositol 3-kinase (PI3K). |
| 5309 | 19330070 | The work of numerous different researchers indicates a role of PKB in regulating insulin-stimulated glucose uptake. |
| 5310 | 19330070 | The crucial role of lipid second messengers in PKB activation has been dissected through the use of the PI3K-specific inhibitors wortmannin and LY294002. |
| 5311 | 19330070 | Receptor-activated PI3K synthesizes the lipid second messenger PtdIns[3,4,5]-trisphosphate, leading to the recruitment of PKB to the membrane. |
| 5312 | 19330070 | Activation of PKB alpha is then achieved at the plasma membrane by phosphorylation of Thr308 in the activation-loop of the kinase domain and Ser473 in the carboxy-terminal regulatory region, respectively. 3-Phosphoinositide-dependent protein kinase-1 (PDK1) is responsible for T308 phosphorylation. |
| 5313 | 19330070 | The usage of specific inhibitors and natural compound has significantly contributed to investigate the molecular mechanism of PI3K/PDK1/PKB signaling pathway, leading to the putative therapeutics benefits of patients. |
| 5314 | 19330070 | This review focuses on the contribution of natural inhibitor or compound in our understanding of the mechanism by which insulin induces, especially in PI3K/PDK1/PKB signaling. |
| 5315 | 19336408 | Insulin-induced changes in mtDNA, mitochondrial mass, intracellular ATP content, and transcripts of mitochondrion-associated genes were prevented by blockade of Akt activation with the phosphatidylinositol 3-kinase inhibitor LY294002. |
| 5316 | 19336408 | Finally, insulin suppression of mtDNA, ATP production, and expression of mitochondrion-related genes was largely prevented by inhibition of cyclic nucleotide phosphodiesterase with isobutylmethylxanthine. |
| 5317 | 19365404 | Pancreas-specific Pten deficiency causes partial resistance to diabetes and elevated hepatic AKT signaling. |
| 5318 | 19365404 | PTEN, a negative regulator of the phosphatidylinositol-3-kinase/AKT pathway, is an important modulator of insulin signaling. |
| 5319 | 19365404 | To investigate the mechanism for the resistance to HFD-induced hyperglycemia in PPKO mice, we evaluated AKT phosphorylation in major insulin-responsive tissues: the liver, muscle, and fat. |
| 5320 | 19365404 | We found that Pten loss in the pancreas causes the elevation of AKT signaling in the liver. |
| 5321 | 19365404 | The phosphorylation of AKT and its downstream substrate GSK3beta was increased in the liver of PPKO mice, while PTEN level was decreased without detectable excision of Pten allele in the liver of PPKO mice. |
| 5322 | 19365404 | Proteomics analysis revealed dramatically decreased level of 78-kDa glucose-regulated protein (GRP78) in the liver of PPKO mice, which may also contribute to the lower blood glucose level of PPKO mice fed with HFD. |
| 5323 | 19393315 | Genistein and daidzein upregulated the estrogen receptor ERbeta and increased Bcl-2 expression. |
| 5324 | 19393315 | Moreover, inhibition of the PI3K and Rho A/Rho kinase pathways by wortmannin and Y-27632 altered the effects of genistein and daidzein on cell survival. |
| 5325 | 19393315 | We conclude that oxidative stress-induced apoptosis and cell proliferation inhibition can be prevented by soy isoflavones via the regulation of ERbeta and Bcl-2/Bax expression and modulation of cell survival signaling, such as the PI3K pathway. |
| 5326 | 19393315 | Genistein and daidzein upregulated the estrogen receptor ERbeta and increased Bcl-2 expression. |
| 5327 | 19393315 | Moreover, inhibition of the PI3K and Rho A/Rho kinase pathways by wortmannin and Y-27632 altered the effects of genistein and daidzein on cell survival. |
| 5328 | 19393315 | We conclude that oxidative stress-induced apoptosis and cell proliferation inhibition can be prevented by soy isoflavones via the regulation of ERbeta and Bcl-2/Bax expression and modulation of cell survival signaling, such as the PI3K pathway. |
| 5329 | 19423756 | Insulin and insulin-like growth factor-I receptors differentially mediate insulin-stimulated adhesion molecule production by endothelial cells. |
| 5330 | 19423756 | ECs express abundant IGF-I receptors as well as insulin receptors. |
| 5331 | 19423756 | Whether IGF-I receptors contribute to insulin-induced endothelial production of adhesion molecules is unknown. |
| 5332 | 19423756 | The cellular content of vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) was measured, and monocyte adhesion to ECs was quantified. |
| 5333 | 19423756 | Insulin increased both VCAM-1 (P < 0.001) and ICAM-1 (P < 0.0002) content, which was accompanied by an increased number of monocytes adherent to BAECs (P = 0.0001). |
| 5334 | 19423756 | Inhibition of either MAPK kinase-1 or p38 MAPK but not phosphatidylinositol 3-kinase abolished insulin-mediated production of adhesion molecules. |
| 5335 | 19423756 | Insulin receptor small interfering RNA knockdown abolished insulin-stimulated increases of ICAM-1 but not VCAM-1. |
| 5336 | 19423756 | Conversely, IGF-I receptor blockade with either a neutralizing antibody or specific small interfering RNA eliminated insulin-induced VCAM-1 but not ICAM-1 production. |
| 5337 | 19423756 | Blockade of signaling via either the insulin or IGF-I receptors decreased monocyte adherence to BAECs (P < 0.01 for each). |
| 5338 | 19423756 | We conclude that insulin and IGF-I receptors differentially mediate the production of adhesion molecules by ECs and monocyte adhesion onto the vascular endothelium in response to the hyperinsulinemic state. |
| 5339 | 19443196 | Ferulic acid augments angiogenesis via VEGF, PDGF and HIF-1 alpha. |
| 5340 | 19443196 | Using Western blot analysis and quantitative real-time polymerase chain reaction, we found that ferulic acid increased vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF) expression in HUVECs. |
| 5341 | 19443196 | Furthermore, the amounts of hypoxic-induced factor (HIF) 1 alpha mRNA and protein, the major regulator of VEGF and PDGF, also showed up-regulation by ferulic acid. |
| 5342 | 19443196 | Moreover, inhibitors of extracellular-signal-regulated kinase 1/2 and phosphoinositide-3 kinase (PI3K) abolished the binding activity of HIF-1 alpha and the subsequent activation of VEGF and PDGF production by ferulic acid. |
| 5343 | 19443196 | This effect might be observed through the modulation of VEGF, PDGF and HIF-1 alpha. |
| 5344 | 19463904 | Glucagon-like peptide-1 (GLP-1) protects against methylglyoxal-induced PC12 cell apoptosis through the PI3K/Akt/mTOR/GCLc/redox signaling pathway. |
| 5345 | 19463904 | Cell apoptosis, expression and phosphorylation of phosphatidylinositol-3 kinase/Akt/mammalian target of rapamycin/gamma-glutamylcysteine ligase catalytic subunit (GCLc), and redox balance were then determined. |
| 5346 | 19463904 | GLP-1 protected against this MG-induced apoptosis, which corresponded to the phosphorylation of PI3K, Akt, and mTOR, as well as the upregulation of GCLc and the restoration of the redox imbalance. |
| 5347 | 19463904 | Inhibitors of PI3K (LY294002), Akt (Akt-I), and mTOR (rapamycin) reduced the GLP-1-induced GCLc upregulation and its protection against MG-induced PC12 apoptosis. |
| 5348 | 19463904 | In conclusion, the neuroprotective effect of GLP-1 is due to an enhancement of PI3K/Akt/mTOR/GCLc/redox signaling. |
| 5349 | 19463904 | Glucagon-like peptide-1 (GLP-1) protects against methylglyoxal-induced PC12 cell apoptosis through the PI3K/Akt/mTOR/GCLc/redox signaling pathway. |
| 5350 | 19463904 | Cell apoptosis, expression and phosphorylation of phosphatidylinositol-3 kinase/Akt/mammalian target of rapamycin/gamma-glutamylcysteine ligase catalytic subunit (GCLc), and redox balance were then determined. |
| 5351 | 19463904 | GLP-1 protected against this MG-induced apoptosis, which corresponded to the phosphorylation of PI3K, Akt, and mTOR, as well as the upregulation of GCLc and the restoration of the redox imbalance. |
| 5352 | 19463904 | Inhibitors of PI3K (LY294002), Akt (Akt-I), and mTOR (rapamycin) reduced the GLP-1-induced GCLc upregulation and its protection against MG-induced PC12 apoptosis. |
| 5353 | 19463904 | In conclusion, the neuroprotective effect of GLP-1 is due to an enhancement of PI3K/Akt/mTOR/GCLc/redox signaling. |
| 5354 | 19463904 | Glucagon-like peptide-1 (GLP-1) protects against methylglyoxal-induced PC12 cell apoptosis through the PI3K/Akt/mTOR/GCLc/redox signaling pathway. |
| 5355 | 19463904 | Cell apoptosis, expression and phosphorylation of phosphatidylinositol-3 kinase/Akt/mammalian target of rapamycin/gamma-glutamylcysteine ligase catalytic subunit (GCLc), and redox balance were then determined. |
| 5356 | 19463904 | GLP-1 protected against this MG-induced apoptosis, which corresponded to the phosphorylation of PI3K, Akt, and mTOR, as well as the upregulation of GCLc and the restoration of the redox imbalance. |
| 5357 | 19463904 | Inhibitors of PI3K (LY294002), Akt (Akt-I), and mTOR (rapamycin) reduced the GLP-1-induced GCLc upregulation and its protection against MG-induced PC12 apoptosis. |
| 5358 | 19463904 | In conclusion, the neuroprotective effect of GLP-1 is due to an enhancement of PI3K/Akt/mTOR/GCLc/redox signaling. |
| 5359 | 19463904 | Glucagon-like peptide-1 (GLP-1) protects against methylglyoxal-induced PC12 cell apoptosis through the PI3K/Akt/mTOR/GCLc/redox signaling pathway. |
| 5360 | 19463904 | Cell apoptosis, expression and phosphorylation of phosphatidylinositol-3 kinase/Akt/mammalian target of rapamycin/gamma-glutamylcysteine ligase catalytic subunit (GCLc), and redox balance were then determined. |
| 5361 | 19463904 | GLP-1 protected against this MG-induced apoptosis, which corresponded to the phosphorylation of PI3K, Akt, and mTOR, as well as the upregulation of GCLc and the restoration of the redox imbalance. |
| 5362 | 19463904 | Inhibitors of PI3K (LY294002), Akt (Akt-I), and mTOR (rapamycin) reduced the GLP-1-induced GCLc upregulation and its protection against MG-induced PC12 apoptosis. |
| 5363 | 19463904 | In conclusion, the neuroprotective effect of GLP-1 is due to an enhancement of PI3K/Akt/mTOR/GCLc/redox signaling. |
| 5364 | 19463904 | Glucagon-like peptide-1 (GLP-1) protects against methylglyoxal-induced PC12 cell apoptosis through the PI3K/Akt/mTOR/GCLc/redox signaling pathway. |
| 5365 | 19463904 | Cell apoptosis, expression and phosphorylation of phosphatidylinositol-3 kinase/Akt/mammalian target of rapamycin/gamma-glutamylcysteine ligase catalytic subunit (GCLc), and redox balance were then determined. |
| 5366 | 19463904 | GLP-1 protected against this MG-induced apoptosis, which corresponded to the phosphorylation of PI3K, Akt, and mTOR, as well as the upregulation of GCLc and the restoration of the redox imbalance. |
| 5367 | 19463904 | Inhibitors of PI3K (LY294002), Akt (Akt-I), and mTOR (rapamycin) reduced the GLP-1-induced GCLc upregulation and its protection against MG-induced PC12 apoptosis. |
| 5368 | 19463904 | In conclusion, the neuroprotective effect of GLP-1 is due to an enhancement of PI3K/Akt/mTOR/GCLc/redox signaling. |
| 5369 | 19472218 | Phospholipid transfer protein reduces phosphorylation of tau in human neuronal cells. |
| 5370 | 19472218 | In this study we provide evidence that phospholipid transfer protein (PLTP), one of the main lipid transfer proteins in the brain, significantly reduces levels of phosphorylated tau and increases levels of the inactive form of glycogen synthase kinase-3beta (GSK3 beta) in HCN2 cells. |
| 5371 | 19472218 | Furthermore, inhibition of phosphatidylinositol-3 kinase (PI3K) reversed the PLTP-induced increase in levels of GSK3 beta phosphorylated at serine 9 (pGSK3 beta(Ser9)) and partially reversed the PLTP-induced reduction in tau phosphorylation. |
| 5372 | 19472218 | We provide evidence that the PLTP-induced changes are not due to activation of Disabled-1 (Dab1), insofar as PLTP reduced levels of total and phosphorylated Dab1 in HCN2 cells. |
| 5373 | 19472218 | We have also shown that inhibition of tyrosine kinase activity of insulin receptor (IR) and/or insulin-like growth factor 1 (IGF1) receptor (IGFR) reverses the PLTP-induced increase in levels of phosphorylated Akt (pAkt(Thr308) and pAkt(Ser473)), suggesting that PLTP-mediated activation of the PI3K/Akt pathway is dependent on IR/IGFR receptor tyrosine kinase activity. |
| 5374 | 19472218 | Phospholipid transfer protein reduces phosphorylation of tau in human neuronal cells. |
| 5375 | 19472218 | In this study we provide evidence that phospholipid transfer protein (PLTP), one of the main lipid transfer proteins in the brain, significantly reduces levels of phosphorylated tau and increases levels of the inactive form of glycogen synthase kinase-3beta (GSK3 beta) in HCN2 cells. |
| 5376 | 19472218 | Furthermore, inhibition of phosphatidylinositol-3 kinase (PI3K) reversed the PLTP-induced increase in levels of GSK3 beta phosphorylated at serine 9 (pGSK3 beta(Ser9)) and partially reversed the PLTP-induced reduction in tau phosphorylation. |
| 5377 | 19472218 | We provide evidence that the PLTP-induced changes are not due to activation of Disabled-1 (Dab1), insofar as PLTP reduced levels of total and phosphorylated Dab1 in HCN2 cells. |
| 5378 | 19472218 | We have also shown that inhibition of tyrosine kinase activity of insulin receptor (IR) and/or insulin-like growth factor 1 (IGF1) receptor (IGFR) reverses the PLTP-induced increase in levels of phosphorylated Akt (pAkt(Thr308) and pAkt(Ser473)), suggesting that PLTP-mediated activation of the PI3K/Akt pathway is dependent on IR/IGFR receptor tyrosine kinase activity. |
| 5379 | 19531636 | Although cutaneous SHH and Patched-1 (Ptc-1 encoded by PTCH, PTCH 1) proteins were increased significantly on day 4 after wounding compared with day 0 in normal mice, both were decreased significantly in STZ-induced diabetic mice. |
| 5380 | 19531636 | Topical application of SHH restored wound healing delay in STZ-induced diabetic mice, with a concomitant augmentation of both cutaneous constitutive nitric oxide synthase (NOS) activity and nitrite level. |
| 5381 | 19531636 | After 24-h treatment in vitro, SHH (5-20 microg/ml) significantly increased cutaneous endothelial NOS protein expression, NOS activity and NO level in normal mice and STZ-induced diabetic mice in a concentration-dependent manner, an effect that was blunted by cyclopamine and NOS inhibitor N(omega)-nitro-L-arginine methyl ester. |
| 5382 | 19531636 | The phosphatidylinositol 3-kinase inhibitor LY-294002 significantly blunted the increase of NOS activity and NO level induced by SHH treatment in human umbilican vein endothelial cells. |
| 5383 | 19541499 | Akt and PTEN: beta-cell mass and pancreas plasticity. |
| 5384 | 19541499 | The insulin receptor substrate (insulin receptor 2/phosphoinositide 3-kinase [PI3K]) pathway plays a crucial part in regulating beta-cell mass and function. |
| 5385 | 19541499 | The serine-threonine kinase Akt, also known as protein kinase B, is one of the major downstream targets of the PI3K pathway and is negatively regulated by phosphatase and tensin homologue deleted on chromosome 10. |
| 5386 | 19541499 | Akt and PTEN: beta-cell mass and pancreas plasticity. |
| 5387 | 19541499 | The insulin receptor substrate (insulin receptor 2/phosphoinositide 3-kinase [PI3K]) pathway plays a crucial part in regulating beta-cell mass and function. |
| 5388 | 19541499 | The serine-threonine kinase Akt, also known as protein kinase B, is one of the major downstream targets of the PI3K pathway and is negatively regulated by phosphatase and tensin homologue deleted on chromosome 10. |
| 5389 | 19574203 | As hyperactivation of the pharmacologically targetable PI3K/mTOR/p70S6K1 axis appears to be central to the occurrence of lapatinib resistance, preclinical data showing enhanced antitumour effects when combining lapatinib with mTOR inhibitors (e.g., rapamycin analogues and NVP-BEZ235) highlight the importance of translational work to yield clinically useful regimens capable of delaying or treating lapatinib resistance. |
| 5390 | 19587264 | The translocation and localization of glucose transporter 4 (GLUT4) to the adipocyte plasma membrane were impaired in TH mice compared to control C57BL6/J (B6) mice. |
| 5391 | 19587264 | These defects were associated with decreased GLUT4 protein, reduced phosphatidylinositol 3-kinase activity, and alterations in the phosphorylation status of insulin receptor substrate 1 (IRS1). |
| 5392 | 19587264 | Activation of c-Jun N-terminal kinase 1/2, which can phosphorylate IRS1 on Ser307, was significantly higher in TH mice compared with B6 controls. |
| 5393 | 19587264 | Immunoprecipitation with anti-ubiquitin and western blot analysis of IRS1 protein revealed increased total IRS1 ubiquitination in adipose tissue of TH mice. |
| 5394 | 19587264 | Suppressor of cytokine signaling 1, known to promote IRS1 ubiquitination and subsequent degradation, was found at significantly higher levels in TH mice compared with B6. |
| 5395 | 19587264 | Our findings suggest that increased IRS1 degradation and subsequent impaired GLUT4 mobilization play a role in the reduced glucose uptake in insulin resistant TH mice. |
| 5396 | 19638643 | We showed that light stimulates various components of the PI cycle in the vertebrate ROS, including diacylglycerol kinase, PI synthetase, phosphatidylinositol phosphate kinase, phospholipase C, and phosphoinositide 3-kinase (PI3K). |
| 5397 | 19639221 | Bis(maltolato)-oxovanadium (IV)-induced phosphorylation of PKB, GSK-3 and FOXO1 contributes to its glucoregulatory responses (review). |
| 5398 | 19639221 | While the precise molecular mechanism by which BMOV exerts its insulin-mimetic effects remains poorly defined, studies have shown that BMOV is a potent activator of several key components of the insulin signaling pathways, such as phosphatidyl-inositol 3-kinase (PI3-K), and its downstream effector, protein kinase B (PKB). |
| 5399 | 19639221 | In addition, BMOV-induced phosphorylation of PKB has also been associated with the enhanced phosphorylation of glycogen synthase kinase-3 (GSK-3) and forkhead box protein 1 (FOXO1). |
| 5400 | 19639221 | Since PKB is instrumental in mediating the effects of insulin on glucose transport, glycogen synthesis and gluconeogenesis, it is reasonable to suggest that activation of this pathway by BMOV serves as a mechanism for its insulin-like effects. |
| 5401 | 19647727 | Moreover, CDCQ-induced nuclear translocation of the transcription factor NF-E2-related factor 2 (Nrf2), which is upstream of CDCQ-induced HO-1 expression, and PI3K/Akt activation, a pathway that is involved in induced Nrf2 nuclear translocation. |
| 5402 | 19647727 | Taken together, these results suggest that the protective effects of CDCQ against t-BHP-induced hepatotoxicity may be due, at least in part, to its ability to scavenge ROS and to regulate the antioxidant enzyme HO-1 via the PI3K/Akt-Nrf2 signaling pathways. |
| 5403 | 19647727 | Moreover, CDCQ-induced nuclear translocation of the transcription factor NF-E2-related factor 2 (Nrf2), which is upstream of CDCQ-induced HO-1 expression, and PI3K/Akt activation, a pathway that is involved in induced Nrf2 nuclear translocation. |
| 5404 | 19647727 | Taken together, these results suggest that the protective effects of CDCQ against t-BHP-induced hepatotoxicity may be due, at least in part, to its ability to scavenge ROS and to regulate the antioxidant enzyme HO-1 via the PI3K/Akt-Nrf2 signaling pathways. |
| 5405 | 19657716 | PEDF inhibits VEGF- and EPO- induced angiogenesis in retinal endothelial cells through interruption of PI3K/Akt phosphorylation. |
| 5406 | 19657716 | The main pathological feature of proliferative diabetic retinopathy (PDR) is hypoxia, and overproduction of growth factors like vascular endothelial growth factor (VEGF) and erythropoietin (Epo). |
| 5407 | 19657716 | Pigment epithelium-derived factor (PEDF), a 50-kDa protein secreted by retinal pigment epithelium, inhibits the growth of new blood vessel induced in the eye in a variety of ways with a yet elusive mechanism. |
| 5408 | 19657716 | Here, we investigated the possible mechanism by which PEDF inhibits VEGF- and Epo-induced angiogenic effects in RECs is mediated through PI3K/Akt pathway. |
| 5409 | 19657716 | PEDF treatment induced the apoptosis in RECs by activating caspase-3 and DNA fragmentation. |
| 5410 | 19657716 | We found a dose-dependent increase in cell survival with VEGF or Epo, which was attenuated in the presence of PEDF. |
| 5411 | 19657716 | In addition, PEDF significantly (P < 0.05) inhibited migration and in vitro tube formation in RECs in the presence of VEGF as like PI3K/Akt inhibitor. |
| 5412 | 19657716 | Of interest, PEDF effectively abrogated VEGF-mediated phosphorylation of PI3K/Akt. |
| 5413 | 19657716 | Further studies using RECs transfected with constitutively active and dominant-negative forms of Akt suggest that PEDF could inhibit VEGF- and also Epo-induced angiogenesis by disruption of PI3K/Akt signaling. |
| 5414 | 19657716 | PEDF inhibits VEGF- and EPO- induced angiogenesis in retinal endothelial cells through interruption of PI3K/Akt phosphorylation. |
| 5415 | 19657716 | The main pathological feature of proliferative diabetic retinopathy (PDR) is hypoxia, and overproduction of growth factors like vascular endothelial growth factor (VEGF) and erythropoietin (Epo). |
| 5416 | 19657716 | Pigment epithelium-derived factor (PEDF), a 50-kDa protein secreted by retinal pigment epithelium, inhibits the growth of new blood vessel induced in the eye in a variety of ways with a yet elusive mechanism. |
| 5417 | 19657716 | Here, we investigated the possible mechanism by which PEDF inhibits VEGF- and Epo-induced angiogenic effects in RECs is mediated through PI3K/Akt pathway. |
| 5418 | 19657716 | PEDF treatment induced the apoptosis in RECs by activating caspase-3 and DNA fragmentation. |
| 5419 | 19657716 | We found a dose-dependent increase in cell survival with VEGF or Epo, which was attenuated in the presence of PEDF. |
| 5420 | 19657716 | In addition, PEDF significantly (P < 0.05) inhibited migration and in vitro tube formation in RECs in the presence of VEGF as like PI3K/Akt inhibitor. |
| 5421 | 19657716 | Of interest, PEDF effectively abrogated VEGF-mediated phosphorylation of PI3K/Akt. |
| 5422 | 19657716 | Further studies using RECs transfected with constitutively active and dominant-negative forms of Akt suggest that PEDF could inhibit VEGF- and also Epo-induced angiogenesis by disruption of PI3K/Akt signaling. |
| 5423 | 19657716 | PEDF inhibits VEGF- and EPO- induced angiogenesis in retinal endothelial cells through interruption of PI3K/Akt phosphorylation. |
| 5424 | 19657716 | The main pathological feature of proliferative diabetic retinopathy (PDR) is hypoxia, and overproduction of growth factors like vascular endothelial growth factor (VEGF) and erythropoietin (Epo). |
| 5425 | 19657716 | Pigment epithelium-derived factor (PEDF), a 50-kDa protein secreted by retinal pigment epithelium, inhibits the growth of new blood vessel induced in the eye in a variety of ways with a yet elusive mechanism. |
| 5426 | 19657716 | Here, we investigated the possible mechanism by which PEDF inhibits VEGF- and Epo-induced angiogenic effects in RECs is mediated through PI3K/Akt pathway. |
| 5427 | 19657716 | PEDF treatment induced the apoptosis in RECs by activating caspase-3 and DNA fragmentation. |
| 5428 | 19657716 | We found a dose-dependent increase in cell survival with VEGF or Epo, which was attenuated in the presence of PEDF. |
| 5429 | 19657716 | In addition, PEDF significantly (P < 0.05) inhibited migration and in vitro tube formation in RECs in the presence of VEGF as like PI3K/Akt inhibitor. |
| 5430 | 19657716 | Of interest, PEDF effectively abrogated VEGF-mediated phosphorylation of PI3K/Akt. |
| 5431 | 19657716 | Further studies using RECs transfected with constitutively active and dominant-negative forms of Akt suggest that PEDF could inhibit VEGF- and also Epo-induced angiogenesis by disruption of PI3K/Akt signaling. |
| 5432 | 19657716 | PEDF inhibits VEGF- and EPO- induced angiogenesis in retinal endothelial cells through interruption of PI3K/Akt phosphorylation. |
| 5433 | 19657716 | The main pathological feature of proliferative diabetic retinopathy (PDR) is hypoxia, and overproduction of growth factors like vascular endothelial growth factor (VEGF) and erythropoietin (Epo). |
| 5434 | 19657716 | Pigment epithelium-derived factor (PEDF), a 50-kDa protein secreted by retinal pigment epithelium, inhibits the growth of new blood vessel induced in the eye in a variety of ways with a yet elusive mechanism. |
| 5435 | 19657716 | Here, we investigated the possible mechanism by which PEDF inhibits VEGF- and Epo-induced angiogenic effects in RECs is mediated through PI3K/Akt pathway. |
| 5436 | 19657716 | PEDF treatment induced the apoptosis in RECs by activating caspase-3 and DNA fragmentation. |
| 5437 | 19657716 | We found a dose-dependent increase in cell survival with VEGF or Epo, which was attenuated in the presence of PEDF. |
| 5438 | 19657716 | In addition, PEDF significantly (P < 0.05) inhibited migration and in vitro tube formation in RECs in the presence of VEGF as like PI3K/Akt inhibitor. |
| 5439 | 19657716 | Of interest, PEDF effectively abrogated VEGF-mediated phosphorylation of PI3K/Akt. |
| 5440 | 19657716 | Further studies using RECs transfected with constitutively active and dominant-negative forms of Akt suggest that PEDF could inhibit VEGF- and also Epo-induced angiogenesis by disruption of PI3K/Akt signaling. |
| 5441 | 19657716 | PEDF inhibits VEGF- and EPO- induced angiogenesis in retinal endothelial cells through interruption of PI3K/Akt phosphorylation. |
| 5442 | 19657716 | The main pathological feature of proliferative diabetic retinopathy (PDR) is hypoxia, and overproduction of growth factors like vascular endothelial growth factor (VEGF) and erythropoietin (Epo). |
| 5443 | 19657716 | Pigment epithelium-derived factor (PEDF), a 50-kDa protein secreted by retinal pigment epithelium, inhibits the growth of new blood vessel induced in the eye in a variety of ways with a yet elusive mechanism. |
| 5444 | 19657716 | Here, we investigated the possible mechanism by which PEDF inhibits VEGF- and Epo-induced angiogenic effects in RECs is mediated through PI3K/Akt pathway. |
| 5445 | 19657716 | PEDF treatment induced the apoptosis in RECs by activating caspase-3 and DNA fragmentation. |
| 5446 | 19657716 | We found a dose-dependent increase in cell survival with VEGF or Epo, which was attenuated in the presence of PEDF. |
| 5447 | 19657716 | In addition, PEDF significantly (P < 0.05) inhibited migration and in vitro tube formation in RECs in the presence of VEGF as like PI3K/Akt inhibitor. |
| 5448 | 19657716 | Of interest, PEDF effectively abrogated VEGF-mediated phosphorylation of PI3K/Akt. |
| 5449 | 19657716 | Further studies using RECs transfected with constitutively active and dominant-negative forms of Akt suggest that PEDF could inhibit VEGF- and also Epo-induced angiogenesis by disruption of PI3K/Akt signaling. |
| 5450 | 19679877 | Risk factors for AF, including aging, obesity, and diabetes, have been associated with insulin resistance that leads to depressed/defective PI3K signaling. |
| 5451 | 19683528 | PANDER binds to the liver cell membrane and inhibits insulin signaling in HepG2 cells. |
| 5452 | 19683528 | PANDER is a cytokine co-secreted with insulin from islet beta-cells. |
| 5453 | 19683528 | In HepG2 cells, pre-treatment with PANDER ranging from 4 pM to 4 nM for 8h resulted in a maximal inhibition of insulin-stimulated activation of insulin receptor and insulin receptor substrate 1 by 52% and 63%, respectively. |
| 5454 | 19683528 | Moreover, PANDER treatment also reduced insulin-stimulated PI3K and pAkt levels by 55% and 48%, respectively. |
| 5455 | 19683528 | In summary, we have identified the liver as a novel target for PANDER, and PANDER may be involved in the progression of diabetes by regulating hepatic insulin signaling pathways. |
| 5456 | 19706599 | A novel pathway of insulin sensitivity in chromogranin A null mice: a crucial role for pancreastatin in glucose homeostasis. |
| 5457 | 19706599 | Thus, PST action may be mediated by suppressing IRS1/2-phosphatidylinositol 3-kinase-Akt-FOXO-1 signaling and insulin-induced maturation of SREBP1c by PKC and a high level of NO. |
| 5458 | 19718675 | Cardiac mitochondrial-dependent apoptotic pathways, such as Bad, cytosolic cytochrome c, activated caspase 9 and 3, and calcineurin-nuclear factor activation transcription 3 (NFAT3) hypertrophic pathway in DM were increased compared to Control and attenuated in DI group after 8 weeks whereas those were not found after 4 weeks. |
| 5459 | 19718675 | Insulin-like growth factor-I receptor (IGFIR), phosphatidylinositol 3'-kinase (PI3K), and the protein kinase B (Akt) were significantly decreased in DM relative to Control and DI after 8 weeks whereas those were not found after 4 weeks. |
| 5460 | 19718675 | Insulin replacement not only prevents activation of the cardiac mitochondrial-dependent apoptotic pathway and calcineurin-related NFAT3 hypertrophic pathway in diabetes but it also enhances the cardiac insulin/IGFIR-PI3K-Akt survival pathway, all of which are attenuated with insulin therapeutic duration-dependent manners. |
| 5461 | 19721352 | In addition, quantitative RT-PCR was used to determine changes in insulin signaling gene (insulin receptor substrate (IRS)-1, IRS-2 and phosphatidylinositol 3-kinase (PI3-K) P85alpha) mRNA levels in peripheral leukocytes. |
| 5462 | 19721352 | In peripheral leukocytes, the IRS-2 and PI3-K p85alpha mRNA levels significantly increased, and a significant increase in pyruvate kinase and pyruvate carboxylase activity, two enzymes involved in cellular energy metabolism, was also observed post treatment. |
| 5463 | 19721352 | In addition, quantitative RT-PCR was used to determine changes in insulin signaling gene (insulin receptor substrate (IRS)-1, IRS-2 and phosphatidylinositol 3-kinase (PI3-K) P85alpha) mRNA levels in peripheral leukocytes. |
| 5464 | 19721352 | In peripheral leukocytes, the IRS-2 and PI3-K p85alpha mRNA levels significantly increased, and a significant increase in pyruvate kinase and pyruvate carboxylase activity, two enzymes involved in cellular energy metabolism, was also observed post treatment. |
| 5465 | 19759515 | These responses were related to increased association of PI3K with the glucocorticoid receptor (GR). |
| 5466 | 19759515 | Fluorescence resonance energy transfer and an in vitro competition assay revealed that activated GRs competed for PI3K, reducing its association with IRS-1. |
| 5467 | 19759515 | These responses were related to increased association of PI3K with the glucocorticoid receptor (GR). |
| 5468 | 19759515 | Fluorescence resonance energy transfer and an in vitro competition assay revealed that activated GRs competed for PI3K, reducing its association with IRS-1. |
| 5469 | 19763973 | We further present examples for the application of biochemical assays to characterize the ligand-induced kinase activation of PI3K, GSK3, and ERK2. |
| 5470 | 19797203 | LL-37 via EGFR transactivation to promote high glucose-attenuated epithelial wound healing in organ-cultured corneas. |
| 5471 | 19797203 | The authors investigated the effects of antimicrobial peptide LL-37 on HG-attenuated corneal epithelial EGFR signaling and wound closure. |
| 5472 | 19797203 | Heparin-binding EGF-like growth factor (HB-EGF) shedding was assessed by measuring the release of alkaline phosphatase (AP) in a stable HCEC line expressing HB-EGF-AP. |
| 5473 | 19797203 | Activation of EGFR, phosphoinositide 3-kinase (PI3K), and extracellular signal-regulated kinases 1/2 (ERK1/2) was determined by Western blot analysis. |
| 5474 | 19797203 | LL-37 induced HB-EGF-AP release and EGFR activation in a dose-dependent manner. |
| 5475 | 19797203 | LL-37 prolonged EGFR signaling in response to wounding. |
| 5476 | 19797203 | LL-37 enhanced the closure of a scratch wound in cultured HCECs and partially rescued HG-attenuated wound healing in an EGFR- and a PI3K-dependent manner and restored HG-impaired EGFR signaling in cultured porcine corneas. |
| 5477 | 19797203 | LL-37 is a tonic factor promoting EGFR signaling and enhancing epithelial wound healing in normal and high glucose conditions. |
| 5478 | 19797203 | LL-37 via EGFR transactivation to promote high glucose-attenuated epithelial wound healing in organ-cultured corneas. |
| 5479 | 19797203 | The authors investigated the effects of antimicrobial peptide LL-37 on HG-attenuated corneal epithelial EGFR signaling and wound closure. |
| 5480 | 19797203 | Heparin-binding EGF-like growth factor (HB-EGF) shedding was assessed by measuring the release of alkaline phosphatase (AP) in a stable HCEC line expressing HB-EGF-AP. |
| 5481 | 19797203 | Activation of EGFR, phosphoinositide 3-kinase (PI3K), and extracellular signal-regulated kinases 1/2 (ERK1/2) was determined by Western blot analysis. |
| 5482 | 19797203 | LL-37 induced HB-EGF-AP release and EGFR activation in a dose-dependent manner. |
| 5483 | 19797203 | LL-37 prolonged EGFR signaling in response to wounding. |
| 5484 | 19797203 | LL-37 enhanced the closure of a scratch wound in cultured HCECs and partially rescued HG-attenuated wound healing in an EGFR- and a PI3K-dependent manner and restored HG-impaired EGFR signaling in cultured porcine corneas. |
| 5485 | 19797203 | LL-37 is a tonic factor promoting EGFR signaling and enhancing epithelial wound healing in normal and high glucose conditions. |
| 5486 | 19800940 | Treadmill exercise improves cognitive function and facilitates nerve growth factor signaling by activating mitogen-activated protein kinase/extracellular signal-regulated kinase1/2 in the streptozotocin-induced diabetic rat hippocampus. |
| 5487 | 19800940 | We investigated the effects of regular treadmill exercise for 6 weeks on NGF, tyrosine kinase receptor A (TrkA), p75 receptor, phosphatidylinositol 3-kinase (PI3-K), mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase 1/2 (Erk1/2), cyclic AMP response element-binding protein (CREB), and caspase-3 protein levels; we also assessed cell survival and cognitive function. |
| 5488 | 19800940 | Increased 5-bromo-2'-deoxyuridine-5'-mono-phosphate (BrdU)-labeled cells (P<0.001) and significant increases in NGF and TrkA protein levels were observed in the hippocampal dentate gyrus in the NEG and DEG (P<0.001 and P<0.01, respectively). |
| 5489 | 19800940 | These results show that treadmill exercise improves cognitive function, increases the number of BrdU-labeled cells, and increases NGF levels, by the activation of the MAPK/Erk1/2 signaling pathway in the hippocampus of diabetic rats. |
| 5490 | 19805130 | In particular, insulin resistance was rapidly reversible upon exposure to agents that act as mitochondrial uncouplers, ETC inhibitors, or mitochondrial superoxide dismutase (MnSOD) mimetics. |
| 5491 | 19805130 | Furthermore, acute induction of mitochondrial superoxide production using the complex III antagonist antimycin A caused rapid attenuation of insulin action independently of changes in the canonical PI3K/Akt pathway. |
| 5492 | 19805130 | These results were validated in vivo in that MnSOD transgenic mice were partially protected against HFD induced insulin resistance and MnSOD+/- mice were glucose intolerant on a standard chow diet. |
| 5493 | 19808019 | In recent years it has become apparent that ROS generation in response to physiological stimuli such as insulin may also facilitate signaling by reversibly oxidizing and inhibiting protein tyrosine phosphatases (PTPs). |
| 5494 | 19808019 | Here we report that mice lacking one of the key enzymes involved in the elimination of physiological ROS, glutathione peroxidase 1 (Gpx1), were protected from high-fat-diet-induced insulin resistance. |
| 5495 | 19808019 | The increased insulin sensitivity in Gpx1(-/-) mice was attributed to insulin-induced phosphatidylinositol-3-kinase/Akt signaling and glucose uptake in muscle and could be reversed by the antioxidant N-acetylcysteine. |
| 5496 | 19808019 | Increased insulin signaling correlated with enhanced oxidation of the PTP family member PTEN, which terminates signals generated by phosphatidylinositol-3-kinase. |
| 5497 | 19808019 | In recent years it has become apparent that ROS generation in response to physiological stimuli such as insulin may also facilitate signaling by reversibly oxidizing and inhibiting protein tyrosine phosphatases (PTPs). |
| 5498 | 19808019 | Here we report that mice lacking one of the key enzymes involved in the elimination of physiological ROS, glutathione peroxidase 1 (Gpx1), were protected from high-fat-diet-induced insulin resistance. |
| 5499 | 19808019 | The increased insulin sensitivity in Gpx1(-/-) mice was attributed to insulin-induced phosphatidylinositol-3-kinase/Akt signaling and glucose uptake in muscle and could be reversed by the antioxidant N-acetylcysteine. |
| 5500 | 19808019 | Increased insulin signaling correlated with enhanced oxidation of the PTP family member PTEN, which terminates signals generated by phosphatidylinositol-3-kinase. |
| 5501 | 19826769 | We have isolated mahanine, a carbazole alkaloid, from the leaves of Murraya koenegii that prevented palmitate-induced inhibition of insulin-stimulated phosphorylation of IRbeta, PI3K, PDK1, and Akt in L6 myotubes. |
| 5502 | 19845509 | Downstream targets of these mediators include diverse signalling molecules such as MAPKs (mitogen-activated protein kinases), PI3K (phosphoinositide 3-kinase) and PKC (protein kinase C). |
| 5503 | 19857065 | Inulin increases glucose transport in C2C12 myotubes and HepG2 cells via activation of AMP-activated protein kinase and phosphatidylinositol 3-kinase pathways. |
| 5504 | 19857065 | In this study, we showed that inulin increased the uptake of glucose in C2C12 myotubes, which was associated with both AMP-activated protein kinase (AMPK) and phosphatidylinositol 3-kinase (PI3-K) signaling pathways, but both of these pathways appeared to transmit their signals in an independent manner. |
| 5505 | 19857065 | Collectively, we report the antidiabetic activity of inulin and further demonstrate for the first time that such activity is associated with AMPK and PI3-K activation. |
| 5506 | 19857065 | Inulin increases glucose transport in C2C12 myotubes and HepG2 cells via activation of AMP-activated protein kinase and phosphatidylinositol 3-kinase pathways. |
| 5507 | 19857065 | In this study, we showed that inulin increased the uptake of glucose in C2C12 myotubes, which was associated with both AMP-activated protein kinase (AMPK) and phosphatidylinositol 3-kinase (PI3-K) signaling pathways, but both of these pathways appeared to transmit their signals in an independent manner. |
| 5508 | 19857065 | Collectively, we report the antidiabetic activity of inulin and further demonstrate for the first time that such activity is associated with AMPK and PI3-K activation. |
| 5509 | 19857065 | Inulin increases glucose transport in C2C12 myotubes and HepG2 cells via activation of AMP-activated protein kinase and phosphatidylinositol 3-kinase pathways. |
| 5510 | 19857065 | In this study, we showed that inulin increased the uptake of glucose in C2C12 myotubes, which was associated with both AMP-activated protein kinase (AMPK) and phosphatidylinositol 3-kinase (PI3-K) signaling pathways, but both of these pathways appeared to transmit their signals in an independent manner. |
| 5511 | 19857065 | Collectively, we report the antidiabetic activity of inulin and further demonstrate for the first time that such activity is associated with AMPK and PI3-K activation. |
| 5512 | 19879746 | Moreover, folic acid caused a reduction in PTEN (phosphatase and tensin homolog deleted on chromosome 10) expression, an increase in the phosphorylation of endothelial nitric oxide synthase (eNOS(Ser1177)) and Akt(Ser473), and an enhanced interaction of heat shock protein 90 (HSP90) with eNOS in both strains, with greater magnitude observed in +db/+db mice. |
| 5513 | 19879746 | The mechanism may be, at least partly, attributed to enhancement of PI3K/HSP90/eNOS/Akt cascade, reduction in plasma resistin level, down-regulation of PTEN and slight modification of oxidative state. |
| 5514 | 19897488 | Cluster analysis of insulin action in adipocytes reveals a key role for Akt at the plasma membrane. |
| 5515 | 19897488 | The phosphatidylinositol 3-kinase/Akt pathway regulates many biological processes, including insulin-regulated GLUT4 insertion into the plasma membrane. |
| 5516 | 19897488 | However, Akt operates well below its capacity to facilitate maximal GLUT4 translocation. |
| 5517 | 19897488 | This revealed a strong relationship between phosphorylation of Akt substrates and GLUT4 translocation but not whole cell Akt phosphorylation. |
| 5518 | 19897488 | In contrast, Akt activity at the plasma membrane strongly correlated with GLUT4 translocation and Akt substrate phosphorylation. |
| 5519 | 19902931 | This method has been tested on human T-cells grown in presence and absence of pervanadate and with or without a PI3-K inhibitor and on human glioblastoma cells (U-87 MG) grown in presence and absence of wortmannin (PI3-K inhibitor).The results of T cells suggest that the levels of Akt phosphorylation in untreated cells were below 1% for both phosphorylation sites. |
| 5520 | 19913855 | In the present study, the influence of leucine supplementation on metabolic parameters, insulin secretion to glucose and to amino acids, as well as the levels of proteins that participate in the phosphatidylinositol 3-phosphate kinase (PI3K) pathway was investigated in malnourished rats. |
| 5521 | 19913855 | Both NPL and LPL rats had higher circulating insulin levels than controls. |
| 5522 | 19913855 | The LPL rats also showed increased insulin secretion by pancreatic islets in response to glucose or arginine compared with those observed in islets from LP animals. |
| 5523 | 19913855 | Western blotting analysis demonstrated increased PI3K and mammalian target protein of rapamycin protein contents in LPL compared with LP islets. |
| 5524 | 19913855 | A significant increase in insulin-induced insulin receptor substrate 1-associated PI3K activation was also observed in LPL compared with LP islets. |
| 5525 | 19913855 | In the present study, the influence of leucine supplementation on metabolic parameters, insulin secretion to glucose and to amino acids, as well as the levels of proteins that participate in the phosphatidylinositol 3-phosphate kinase (PI3K) pathway was investigated in malnourished rats. |
| 5526 | 19913855 | Both NPL and LPL rats had higher circulating insulin levels than controls. |
| 5527 | 19913855 | The LPL rats also showed increased insulin secretion by pancreatic islets in response to glucose or arginine compared with those observed in islets from LP animals. |
| 5528 | 19913855 | Western blotting analysis demonstrated increased PI3K and mammalian target protein of rapamycin protein contents in LPL compared with LP islets. |
| 5529 | 19913855 | A significant increase in insulin-induced insulin receptor substrate 1-associated PI3K activation was also observed in LPL compared with LP islets. |
| 5530 | 19913855 | In the present study, the influence of leucine supplementation on metabolic parameters, insulin secretion to glucose and to amino acids, as well as the levels of proteins that participate in the phosphatidylinositol 3-phosphate kinase (PI3K) pathway was investigated in malnourished rats. |
| 5531 | 19913855 | Both NPL and LPL rats had higher circulating insulin levels than controls. |
| 5532 | 19913855 | The LPL rats also showed increased insulin secretion by pancreatic islets in response to glucose or arginine compared with those observed in islets from LP animals. |
| 5533 | 19913855 | Western blotting analysis demonstrated increased PI3K and mammalian target protein of rapamycin protein contents in LPL compared with LP islets. |
| 5534 | 19913855 | A significant increase in insulin-induced insulin receptor substrate 1-associated PI3K activation was also observed in LPL compared with LP islets. |
| 5535 | 19914265 | Alterations in two components of the brain's insulin signaling pathway, docosahexaenoic acid (DHA) content and phosphoinositide 3-kinase (PI3K) activity, have been implicated in the insulin resistance that is central to type II diabetes mellitus (DM). |
| 5536 | 19914265 | Results of the present study suggest that inhibition of PI3K decreases activity and memory while increasing insulin resistance, depression, and anxiety. |
| 5537 | 19914265 | Alterations in two components of the brain's insulin signaling pathway, docosahexaenoic acid (DHA) content and phosphoinositide 3-kinase (PI3K) activity, have been implicated in the insulin resistance that is central to type II diabetes mellitus (DM). |
| 5538 | 19914265 | Results of the present study suggest that inhibition of PI3K decreases activity and memory while increasing insulin resistance, depression, and anxiety. |
| 5539 | 19917721 | Foxo3a transcription factor is critical for muscle atrophy, since it activates the expression of ubiquitin ligase Atrogin-1. |
| 5540 | 19917721 | In several models of atrophy, inhibition of the phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway induces nuclear import of Foxo3a through an Akt-dependent process. |
| 5541 | 19917721 | We observed that after nuclear import of Foxo3a by PI3K/Akt pathway inhibition, activation of stress-activated protein kinase (SAPK) pathways induced nuclear export of Foxo3a through CRM1. |
| 5542 | 19917721 | This mechanism involved the c-Jun NH(2)-terminal kinase (JNK) signaling pathway and was independent of Akt. |
| 5543 | 19917721 | Likewise, we showed that inhibition of p38 induced a massive nuclear relocalization of Foxo3a. |
| 5544 | 19917721 | Our results thus suggest that SAPKs are involved in the control of Foxo3a nucleocytoplasmic translocation in C2C12 cells. |
| 5545 | 19917721 | Moreover, activation of SAPKs decreases the expression of Atrogin-1, and stable C2C12 myotubes, in which the p38 pathway is constitutively activated, present partial protection against atrophy. |
| 5546 | 19917721 | Foxo3a transcription factor is critical for muscle atrophy, since it activates the expression of ubiquitin ligase Atrogin-1. |
| 5547 | 19917721 | In several models of atrophy, inhibition of the phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway induces nuclear import of Foxo3a through an Akt-dependent process. |
| 5548 | 19917721 | We observed that after nuclear import of Foxo3a by PI3K/Akt pathway inhibition, activation of stress-activated protein kinase (SAPK) pathways induced nuclear export of Foxo3a through CRM1. |
| 5549 | 19917721 | This mechanism involved the c-Jun NH(2)-terminal kinase (JNK) signaling pathway and was independent of Akt. |
| 5550 | 19917721 | Likewise, we showed that inhibition of p38 induced a massive nuclear relocalization of Foxo3a. |
| 5551 | 19917721 | Our results thus suggest that SAPKs are involved in the control of Foxo3a nucleocytoplasmic translocation in C2C12 cells. |
| 5552 | 19917721 | Moreover, activation of SAPKs decreases the expression of Atrogin-1, and stable C2C12 myotubes, in which the p38 pathway is constitutively activated, present partial protection against atrophy. |
| 5553 | 19938874 | Moreover, by using two specific inhibitors for PI3K and MAPK signaling, we found that FoxO1 might be the downstream transcription factor of these two pathways. |
| 5554 | 19938874 | Collectively, our findings indicated that FoxO1 modulated by both MAPK and PI3K signaling pathways was prone to cause the proliferation, but not the apoptosis, of pancreatic beta cells exposed to low nutrition, at least partially, by regulating the expression of Ccnd1 at the transcription level. |
| 5555 | 19938874 | Moreover, by using two specific inhibitors for PI3K and MAPK signaling, we found that FoxO1 might be the downstream transcription factor of these two pathways. |
| 5556 | 19938874 | Collectively, our findings indicated that FoxO1 modulated by both MAPK and PI3K signaling pathways was prone to cause the proliferation, but not the apoptosis, of pancreatic beta cells exposed to low nutrition, at least partially, by regulating the expression of Ccnd1 at the transcription level. |
| 5557 | 19955252 | This study demonstrated altered mRNA expression of insulin receptor substrate (IRS)-1, IRS-2, glucose transporter (GLUT)-1, GLUT-4 and glycogen synthase kinase (GSK)-3 isoforms genes in adipose tissue in GDM women in comparison to NGT pregnant controls. |
| 5558 | 19955252 | In skeletal muscle, insulin-controlled GDM was associated with decreased IRS-1, phosphatidylinositol-3-kinase (PI3-K) p85alpha, GLUT-1 and -4, GSK-3 isoforms and phosphoinositide-dependent kinase-1. |
| 5559 | 19955252 | Both adipose tissue and skeletal muscle from women with GDM displayed decreased IRS-1 and GLUT-4 and increased PI3-K p85alpha protein expression. |
| 5560 | 19955252 | Both skeletal muscle and adipose tissue from obese women demonstrated lower GLUT-1 and -4 mRNA expression and diminished GLUT-4 protein expression in skeletal muscle only. |
| 5561 | 19955252 | This study demonstrated altered mRNA expression of insulin receptor substrate (IRS)-1, IRS-2, glucose transporter (GLUT)-1, GLUT-4 and glycogen synthase kinase (GSK)-3 isoforms genes in adipose tissue in GDM women in comparison to NGT pregnant controls. |
| 5562 | 19955252 | In skeletal muscle, insulin-controlled GDM was associated with decreased IRS-1, phosphatidylinositol-3-kinase (PI3-K) p85alpha, GLUT-1 and -4, GSK-3 isoforms and phosphoinositide-dependent kinase-1. |
| 5563 | 19955252 | Both adipose tissue and skeletal muscle from women with GDM displayed decreased IRS-1 and GLUT-4 and increased PI3-K p85alpha protein expression. |
| 5564 | 19955252 | Both skeletal muscle and adipose tissue from obese women demonstrated lower GLUT-1 and -4 mRNA expression and diminished GLUT-4 protein expression in skeletal muscle only. |
| 5565 | 20021289 | SGK1 is activated by insulin and growth factors via the phosphatidylinositol-3-kinase pathway. |
| 5566 | 20021289 | SGK1 regulates ion channels (including ENaC, KCNE1/KCNQ1), carriers (including NCC, NHE3, SGLT1), Na(+)/K(+)-ATPase, enzymes (including glycogen-synthase-kinase-3) and transcription factors (including FOXO3a, ss-catenin, NF-kappaB). |
| 5567 | 20022950 | Dissecting the mechanism of insulin resistance using a novel heterodimerization strategy to activate Akt. |
| 5568 | 20022950 | To explore the mechanism of insulin resistance, we have developed a novel system to activate Akt independently of its upstream effectors as well as other insulin-responsive pathways such as mitogen-activated protein kinase. 3T3-L1 adipocytes were rendered insulin-resistant either with chronic insulin or dexamethasone treatment, but conditional activation of Akt2 stimulated hemagglutinin-tagged glucose transporter 4 translocation to the same extent in these insulin-resistant and control cells. |
| 5569 | 20022950 | However, addition of insulin to cells in which Akt was conditionally activated resulted in a reversion to the insulin-resistant state, indicating a feedforward inhibitory mechanism activated by insulin itself. |
| 5570 | 20022950 | We conclude that in chronic insulin- and dexamethasone-treated cells, acute activation with insulin itself is required to activate a feedforward inhibitory pathway likely emanating from phosphatidylinositol 3-kinase that converges on a target downstream of Akt to cause insulin resistance. |
| 5571 | 20043882 | The death effector domain-containing DEDD forms a complex with Akt and Hsp90, and supports their stability. |
| 5572 | 20043882 | Recently, we found that the death effector domain-containing DEDD inhibits cyclin-dependent kinase-1 (Cdk1) function, thereby preventing Cdk1-dependent inhibitory phosphorylation of S6 kinase-1 (S6K1), downstream of phosphatidylinositol 3-kinase (PI3K), which overall results in maintenance of S6K1 activity. |
| 5573 | 20043882 | Here we newly show that DEDD forms a complex with Akt and heat-shock protein 90 (Hsp90), and supports the stability of both proteins. |
| 5574 | 20043882 | Hence, in DEDD(-/-) mice, Akt protein levels are diminished in skeletal muscles and adipose tissues, which interferes with the translocation of glucose-transporter 4 (GLUT4) upon insulin stimulation, leading to inefficient incorporation of glucose in these organs. |
| 5575 | 20043882 | Interestingly, as for the activation of S6K1, suppression of Cdk1 is involved in the stabilization of Akt protein by DEDD, since diminishment of Cdk1 in DEDD(-/-) cells via siRNA expression or treatment with a Cdk1-inhibitor, increases both Akt and Hsp90 protein levels. |
| 5576 | 20043882 | Such multifaceted involvement of DEDD in glucose homeostasis by supporting both insulin secretion (via maintenance of S6K1 activity) and glucose uptake (via stabilizing Akt protein), may suggest an association of DEDD-deficiency with the pathogenesis of type 2 diabetes mellitus. |
| 5577 | 20051463 | Global phosphoproteomics identifies a major role for AKT and 14-3-3 in regulating EDC3. |
| 5578 | 20051463 | Insulin plays an essential role in metabolic homeostasis in mammals, and many of the underlying biochemical pathways are regulated via the canonical phosphatidylinositol 3-kinase/AKT pathway. |
| 5579 | 20051463 | EDC3, a component of the mRNA decay and translation repression pathway associated with mRNA processing bodies, was shown to be phosphorylated by AKT downstream of insulin signaling. |
| 5580 | 20051961 | A novel inhibitor of the PI3K/Akt pathway based on the structure of inositol 1,3,4,5,6-pentakisphosphate. |
| 5581 | 20061534 | Insulin-feedback via PI3K-C2alpha activated PKBalpha/Akt1 is required for glucose-stimulated insulin secretion. |
| 5582 | 20061534 | Phosphatidylinositide 3-kinases (PI3Ks) play central roles in insulin signal transduction. |
| 5583 | 20061534 | By applying pharmacological inhibitors, transient overexpression and small-interfering RNA-based knockdown of PI3K and PKB/Akt isoforms, together with PI-lipid profiling and live-cell confocal and total internal reflection fluorescence microscopy, we now demonstrate that in response to insulin, PI3K-C2alpha generates PI(3,4)P(2), which allows the selective activation of PKBalpha/Akt1. |
| 5584 | 20061534 | Knockdown of PI3K-C2alpha expression and subsequent reduction of PKBalpha/Akt1 activity in the pancreatic beta-cell impaired glucose-stimulated insulin release, at least in part, due to reduced glucokinase expression and increased AS160 activity. |
| 5585 | 20061534 | Hence, our results identify signal transduction via PI3K-C2alpha as a novel pathway whereby insulin activates PKB/Akt and thus discloses PI3K-C2alpha as a potential drugable target in type 2 diabetes. |
| 5586 | 20061534 | The high degree of codistribution of PI3K-C2alpha and PKBalpha/Akt1 with insulin receptor B type, but not A type, in the same plasma membrane microdomains lends further support to the concept that selectivity in insulin signaling is achieved by the spatial segregation of signaling events. |
| 5587 | 20061534 | Insulin-feedback via PI3K-C2alpha activated PKBalpha/Akt1 is required for glucose-stimulated insulin secretion. |
| 5588 | 20061534 | Phosphatidylinositide 3-kinases (PI3Ks) play central roles in insulin signal transduction. |
| 5589 | 20061534 | By applying pharmacological inhibitors, transient overexpression and small-interfering RNA-based knockdown of PI3K and PKB/Akt isoforms, together with PI-lipid profiling and live-cell confocal and total internal reflection fluorescence microscopy, we now demonstrate that in response to insulin, PI3K-C2alpha generates PI(3,4)P(2), which allows the selective activation of PKBalpha/Akt1. |
| 5590 | 20061534 | Knockdown of PI3K-C2alpha expression and subsequent reduction of PKBalpha/Akt1 activity in the pancreatic beta-cell impaired glucose-stimulated insulin release, at least in part, due to reduced glucokinase expression and increased AS160 activity. |
| 5591 | 20061534 | Hence, our results identify signal transduction via PI3K-C2alpha as a novel pathway whereby insulin activates PKB/Akt and thus discloses PI3K-C2alpha as a potential drugable target in type 2 diabetes. |
| 5592 | 20061534 | The high degree of codistribution of PI3K-C2alpha and PKBalpha/Akt1 with insulin receptor B type, but not A type, in the same plasma membrane microdomains lends further support to the concept that selectivity in insulin signaling is achieved by the spatial segregation of signaling events. |
| 5593 | 20079380 | Exposure of MIN6 cells to ghrelin caused a rapid activation of protein kinase B (PKB) and inhibition of c-Jun N-terminal kinase (JNK) under lipotoxic state. |
| 5594 | 20079380 | Furthermore, LY294002, a PI3K inhibitor, abolished the anti-lipotoxic effect of ghrelin, as well as ghrelin-induced inhibition of JNK, while JNK inhibitor, SP600125 enhanced protective effect of ghrelin on MIN6 cells. |
| 5595 | 20079380 | Ghrelin also inhibited the mitochondrial pathway of apoptosis and it down-regulated Bax in MIN6 cells. |
| 5596 | 20079380 | For secretion experiment, ghrelin suppressed insulin release under palmitate-incubated state. |
| 5597 | 20079380 | Our findings suggest that ghrelin may prevent lipotoxicity-induced apoptosis in MIN6 cells through activation of PKB, inhibition of JNK and mitochondrial pathway. |
| 5598 | 20109524 | Key role of the ERK1/2 MAPK pathway in the transcriptional regulation of the Stearoyl-CoA Desaturase (SCD1) gene expression in response to leptin. |
| 5599 | 20109524 | In liver, many factors regulate SCD1 expression including dietary and hormonal factors such as insulin and leptin. |
| 5600 | 20109524 | We previously showed in hepatic cells that insulin acts through the PI3K and mTOR pathways to upregulate SCD1 expression. |
| 5601 | 20109524 | In the present study, using HepG2 cells, we characterized the signaling pathway mediating the leptin inhibitory response on SCD1 gene expression. |
| 5602 | 20109524 | We showed that leptin inhibits SCD1 at the transcriptional level. |
| 5603 | 20109524 | Inhibition of the ERK1/2 MAPK pathway with the PD98059 reverses the effect of leptin on SCD1 expression. |
| 5604 | 20109524 | Using the pharmaceutical inhibitors Ag490 and SL0101, we showed that the inhibitory effect of leptin is also mediated by the Janus Kinase 2 (Jak2) and p90RSK. |
| 5605 | 20109524 | EMSA and transfection experiments suggest a key role for the Sp1 transcription factor, which in turn may compete for the binding of other transcription factors such as AP-1, leading to the inhibition of SCD1 transcription. |
| 5606 | 20109524 | Taken together, our observations showed that, independently of insulin action, leptin exerts an inhibitory effect on SCD1 transcription via a signaling pathway implicating Jak2, ERK1/2, and p90RSK which probably targets the downstream transcription factor Sp1 on the SCD1 promoter. |
| 5607 | 20117946 | Phosphatidylinositol 3'-kinase (PI3K) and Akt are signaling kinases involved in cell survival and proliferation. |
| 5608 | 20117946 | Recent evidence suggests that PI3K/Akt activates the sterol-regulatory element-binding proteins (SREBPs), master transcriptional regulators of lipid metabolism. |
| 5609 | 20117946 | Phosphatidylinositol 3'-kinase (PI3K) and Akt are signaling kinases involved in cell survival and proliferation. |
| 5610 | 20117946 | Recent evidence suggests that PI3K/Akt activates the sterol-regulatory element-binding proteins (SREBPs), master transcriptional regulators of lipid metabolism. |
| 5611 | 20118282 | Insulin modulates protease-activated receptor 2 signaling: implications for the innate immune response. |
| 5612 | 20118282 | Given the anti-inflammatory effects of insulin in human and animal studies done in vivo and given the signaling pathways in common between insulin and the protease-activated receptor 2 (PAR(2)), a G protein-coupled receptor, we hypothesized that insulin would have an impact on the inflammatory actions of PAR(2). |
| 5613 | 20118282 | We found that low doses or concentrations of insulin in the subnanomolar range reduced PAR(2)-induced inflammation in a murine paw edema model, attenuated PAR(2)-induced leukocyte trafficking in mouse intestinal venules, and reduced PAR(2) calcium signaling in cultured dorsal root ganglion neurons and endothelial cells. |
| 5614 | 20118282 | This effect of insulin to attenuate PAR(2)-mediated inflammation was reversed when cells were preincubated with LY294002 (a PI3K inhibitor) and GF 109203X (a pan-protein kinase C inhibitor). |
| 5615 | 20118282 | The enhanced inflammatory effect of PAR(2) observed in vivo in an insulin-deficient murine type 1 diabetes model was attenuated by the local administration of insulin at the inflammatory site. |
| 5616 | 20118282 | Our data point to an anti-inflammatory action of insulin that targets the acute innate inflammatory response triggered by PAR(2). |
| 5617 | 20132476 | Insulin inhibits Abeta fibrillogenesis through a decrease of the GM1 ganglioside-rich microdomain in neuronal membranes. |
| 5618 | 20132476 | To investigate whether insulin is associated with the assembly of amyloid beta-protein from the cell surface, we treated nerve growth factor (NGF)-treated rat pheochromocytoma 12 (PC12) cells with insulin, which is related to the development of diabetes. |
| 5619 | 20132476 | Insulin treatment induced a decrease in GM1 ganglioside (GM1) levels in detergent-resistant membrane microdomains of NGF-treated PC12 cells. |
| 5620 | 20132476 | The insulin-induced effects on GM1 levels were regulated by a phosphatidylinositol 3-kinase inhibitor, but not by an extracellular signal-regulated kinase inhibitor. |
| 5621 | 20132476 | In addition, insulin failed to induce formation of fibrils from soluble amyloid beta-protein or to accelerate GM1-induced fibril formation. |
| 5622 | 20132476 | Furthermore, assembly of amyloid beta-protein in cultures of NGF-treated PC12 cells was significantly decreased by insulin. |
| 5623 | 20132476 | These results suggest that insulin inhibits amyloid beta-protein assembly by decreasing GM1 expression in detergent-resistant membrane microdomains of neuronal membranes. |
| 5624 | 20140848 | In this short review, an overview over the insulin signalling cascade is given paying special attention to the mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI 3-K)/mammalian target of rapamycin (mTOR) pathways which are involved in protein synthesis and cell growth. |
| 5625 | 20153001 | In addition, phosphatidylinositol-3 kinase and Akt protein expressions were increased when C2C12 myotubes were exposed to IH-901 for up to 3 hours; and these effects including glucose uptake were attenuated by pretreatment with LY294002, a selective phosphatidylinositol-3 kinase inhibitor. |
| 5626 | 20153001 | Protein and gene expression patterns for adenosine monophosphate-activated protein kinase, sterol regulatory element binding protein-1a, and glucose transporter 4 in the liver and skeletal muscles were similar to those in cell studies. |
| 5627 | 20175116 | Further studies revealed that HG treatment resulted in phosphorylation and membrane translocation of Rac1, p47phox, and p67phox subunits leading to NADPH oxidase activation. |
| 5628 | 20175116 | GSPs treatment remarkably disrupted the phosphorylation and membrane translocation of Rac1, p47phox, and p67phox subunits. |
| 5629 | 20175116 | More importantly, our data further revealed that GSPs significantly disrupted HG-induced activation of ERK1/2, JNK1/2, and PI3K/AKT/GSK3beta as well as NF-kappaB signalings, which were dependent on reactive oxygen species (ROS) generation and Rac1 activation. |
| 5630 | 20175116 | In addition, our results also demonstrated that HG-induced cell proliferation and excess ROS production was dependent on the activation of PI3 kinase subunit p110alpha. |
| 5631 | 20175116 | Further studies revealed that HG treatment resulted in phosphorylation and membrane translocation of Rac1, p47phox, and p67phox subunits leading to NADPH oxidase activation. |
| 5632 | 20175116 | GSPs treatment remarkably disrupted the phosphorylation and membrane translocation of Rac1, p47phox, and p67phox subunits. |
| 5633 | 20175116 | More importantly, our data further revealed that GSPs significantly disrupted HG-induced activation of ERK1/2, JNK1/2, and PI3K/AKT/GSK3beta as well as NF-kappaB signalings, which were dependent on reactive oxygen species (ROS) generation and Rac1 activation. |
| 5634 | 20175116 | In addition, our results also demonstrated that HG-induced cell proliferation and excess ROS production was dependent on the activation of PI3 kinase subunit p110alpha. |
| 5635 | 20201383 | We demonstrated the inhibitory property of genipin on INOS expression that possibly occurs via protein kinase A inhibition and stabilization of I-kappaB-NF-kappaB complex. |
| 5636 | 20201383 | Genipin stimulated cNOS activity seemingly activating PI3K/Akt signaling pathway. |
| 5637 | 20212113 | Direct positive regulation of PTEN by the p85 subunit of phosphatidylinositol 3-kinase. |
| 5638 | 20212113 | PI3K consists of a p110 catalytic protein and a p85alpha regulatory protein, required for the stabilization and localization of p110-PI3K activity. |
| 5639 | 20212113 | Here we show another function for the p85alpha regulatory protein: it binds directly to and enhances PTEN lipid phosphatase activity. |
| 5640 | 20212113 | We demonstrate that ectopically expressed FLAG-tagged p85 coimmunoprecipitates endogenous PTEN in an epidermal growth factor dependent manner. |
| 5641 | 20212113 | We also show epidermal growth factor dependent coimmunoprecipitation of endogenous p85 and PTEN proteins in HeLa cells. |
| 5642 | 20212113 | Thus p85 regulates both p110-PI3K and PTEN-phosphatase enzymes through direct interaction. |
| 5643 | 20212113 | This finding underscores the need for caution in analyzing PI3K activity because anti-p85 immunoprecipitations may contain both p85:p110-PI3K and p85:PTEN-phosphatase enzymes and thus measure net PI3K activity. |
| 5644 | 20212113 | We identify the N-terminal SH3-BH region of p85alpha, absent in the smaller p55alpha and p50alpha isoforms, as the region that mediates PTEN binding and regulation. |
| 5645 | 20212113 | The ability of p85 to bind and directly regulate both p110-PI3K and PTEN-PI3-phosphatase allows us to explain the paradoxical insulin signaling phenotypes observed in mice with reduced PI3K or PTEN proteins. |
| 5646 | 20212113 | This discovery will impact ongoing studies using therapeutics targeting the PI3K/PTEN/Akt pathway. |
| 5647 | 20212113 | Direct positive regulation of PTEN by the p85 subunit of phosphatidylinositol 3-kinase. |
| 5648 | 20212113 | PI3K consists of a p110 catalytic protein and a p85alpha regulatory protein, required for the stabilization and localization of p110-PI3K activity. |
| 5649 | 20212113 | Here we show another function for the p85alpha regulatory protein: it binds directly to and enhances PTEN lipid phosphatase activity. |
| 5650 | 20212113 | We demonstrate that ectopically expressed FLAG-tagged p85 coimmunoprecipitates endogenous PTEN in an epidermal growth factor dependent manner. |
| 5651 | 20212113 | We also show epidermal growth factor dependent coimmunoprecipitation of endogenous p85 and PTEN proteins in HeLa cells. |
| 5652 | 20212113 | Thus p85 regulates both p110-PI3K and PTEN-phosphatase enzymes through direct interaction. |
| 5653 | 20212113 | This finding underscores the need for caution in analyzing PI3K activity because anti-p85 immunoprecipitations may contain both p85:p110-PI3K and p85:PTEN-phosphatase enzymes and thus measure net PI3K activity. |
| 5654 | 20212113 | We identify the N-terminal SH3-BH region of p85alpha, absent in the smaller p55alpha and p50alpha isoforms, as the region that mediates PTEN binding and regulation. |
| 5655 | 20212113 | The ability of p85 to bind and directly regulate both p110-PI3K and PTEN-PI3-phosphatase allows us to explain the paradoxical insulin signaling phenotypes observed in mice with reduced PI3K or PTEN proteins. |
| 5656 | 20212113 | This discovery will impact ongoing studies using therapeutics targeting the PI3K/PTEN/Akt pathway. |
| 5657 | 20212113 | Direct positive regulation of PTEN by the p85 subunit of phosphatidylinositol 3-kinase. |
| 5658 | 20212113 | PI3K consists of a p110 catalytic protein and a p85alpha regulatory protein, required for the stabilization and localization of p110-PI3K activity. |
| 5659 | 20212113 | Here we show another function for the p85alpha regulatory protein: it binds directly to and enhances PTEN lipid phosphatase activity. |
| 5660 | 20212113 | We demonstrate that ectopically expressed FLAG-tagged p85 coimmunoprecipitates endogenous PTEN in an epidermal growth factor dependent manner. |
| 5661 | 20212113 | We also show epidermal growth factor dependent coimmunoprecipitation of endogenous p85 and PTEN proteins in HeLa cells. |
| 5662 | 20212113 | Thus p85 regulates both p110-PI3K and PTEN-phosphatase enzymes through direct interaction. |
| 5663 | 20212113 | This finding underscores the need for caution in analyzing PI3K activity because anti-p85 immunoprecipitations may contain both p85:p110-PI3K and p85:PTEN-phosphatase enzymes and thus measure net PI3K activity. |
| 5664 | 20212113 | We identify the N-terminal SH3-BH region of p85alpha, absent in the smaller p55alpha and p50alpha isoforms, as the region that mediates PTEN binding and regulation. |
| 5665 | 20212113 | The ability of p85 to bind and directly regulate both p110-PI3K and PTEN-PI3-phosphatase allows us to explain the paradoxical insulin signaling phenotypes observed in mice with reduced PI3K or PTEN proteins. |
| 5666 | 20212113 | This discovery will impact ongoing studies using therapeutics targeting the PI3K/PTEN/Akt pathway. |
| 5667 | 20212113 | Direct positive regulation of PTEN by the p85 subunit of phosphatidylinositol 3-kinase. |
| 5668 | 20212113 | PI3K consists of a p110 catalytic protein and a p85alpha regulatory protein, required for the stabilization and localization of p110-PI3K activity. |
| 5669 | 20212113 | Here we show another function for the p85alpha regulatory protein: it binds directly to and enhances PTEN lipid phosphatase activity. |
| 5670 | 20212113 | We demonstrate that ectopically expressed FLAG-tagged p85 coimmunoprecipitates endogenous PTEN in an epidermal growth factor dependent manner. |
| 5671 | 20212113 | We also show epidermal growth factor dependent coimmunoprecipitation of endogenous p85 and PTEN proteins in HeLa cells. |
| 5672 | 20212113 | Thus p85 regulates both p110-PI3K and PTEN-phosphatase enzymes through direct interaction. |
| 5673 | 20212113 | This finding underscores the need for caution in analyzing PI3K activity because anti-p85 immunoprecipitations may contain both p85:p110-PI3K and p85:PTEN-phosphatase enzymes and thus measure net PI3K activity. |
| 5674 | 20212113 | We identify the N-terminal SH3-BH region of p85alpha, absent in the smaller p55alpha and p50alpha isoforms, as the region that mediates PTEN binding and regulation. |
| 5675 | 20212113 | The ability of p85 to bind and directly regulate both p110-PI3K and PTEN-PI3-phosphatase allows us to explain the paradoxical insulin signaling phenotypes observed in mice with reduced PI3K or PTEN proteins. |
| 5676 | 20212113 | This discovery will impact ongoing studies using therapeutics targeting the PI3K/PTEN/Akt pathway. |
| 5677 | 20212113 | Direct positive regulation of PTEN by the p85 subunit of phosphatidylinositol 3-kinase. |
| 5678 | 20212113 | PI3K consists of a p110 catalytic protein and a p85alpha regulatory protein, required for the stabilization and localization of p110-PI3K activity. |
| 5679 | 20212113 | Here we show another function for the p85alpha regulatory protein: it binds directly to and enhances PTEN lipid phosphatase activity. |
| 5680 | 20212113 | We demonstrate that ectopically expressed FLAG-tagged p85 coimmunoprecipitates endogenous PTEN in an epidermal growth factor dependent manner. |
| 5681 | 20212113 | We also show epidermal growth factor dependent coimmunoprecipitation of endogenous p85 and PTEN proteins in HeLa cells. |
| 5682 | 20212113 | Thus p85 regulates both p110-PI3K and PTEN-phosphatase enzymes through direct interaction. |
| 5683 | 20212113 | This finding underscores the need for caution in analyzing PI3K activity because anti-p85 immunoprecipitations may contain both p85:p110-PI3K and p85:PTEN-phosphatase enzymes and thus measure net PI3K activity. |
| 5684 | 20212113 | We identify the N-terminal SH3-BH region of p85alpha, absent in the smaller p55alpha and p50alpha isoforms, as the region that mediates PTEN binding and regulation. |
| 5685 | 20212113 | The ability of p85 to bind and directly regulate both p110-PI3K and PTEN-PI3-phosphatase allows us to explain the paradoxical insulin signaling phenotypes observed in mice with reduced PI3K or PTEN proteins. |
| 5686 | 20212113 | This discovery will impact ongoing studies using therapeutics targeting the PI3K/PTEN/Akt pathway. |
| 5687 | 20347724 | Diabetes induces changes in ILK, PINCH and components of related pathways in the spinal cord of rats. |
| 5688 | 20347724 | Expression of ILK, PINCH, PI3K, GSK-3beta, tau, MAP2, synaptophysin and drebrin in the lumbar spinal cord of non-diabetic and streptozotocin-diabetic rats was assessed by Western-blot analysis and immunocytochemistry after 8 and 20weeks of diabetes. |
| 5689 | 20347724 | ILK and PINCH proteins levels were significantly decreased and both colocalized to neurons and oligodendrocytes. |
| 5690 | 20347724 | Phosphorylation of tau and MAP2A/B protein expression were significantly increased, and expression of synaptophysin and drebrin were reduced in diabetic rats. |
| 5691 | 20347724 | Decreased ILK and PINCH as well as alterations of components of related signaling pathways are associated with tau hyperphosphorylation, MAP2 overexpression and reduction of synaptic proteins in the spinal cord of diabetic rats, suggesting that ILK and PINCH contribute to stabilization of axonal and dendritic structures. |
| 5692 | 20348923 | Class Ia phosphoinositide 3-kinase (PI3K), an essential mediator of the metabolic actions of insulin, is composed of a catalytic (p110alpha or p110beta) and regulatory (p85alphaalpha, p85betaalpha or p55alpha) subunit. |
| 5693 | 20348923 | Thus, p85alphaalpha forms a previously unrecognized link between the PI3K pathway, which is central to insulin action, and the regulation of the cellular response to ER stress, a state that when unresolved leads to insulin resistance. |
| 5694 | 20348923 | Class Ia phosphoinositide 3-kinase (PI3K), an essential mediator of the metabolic actions of insulin, is composed of a catalytic (p110alpha or p110beta) and regulatory (p85alphaalpha, p85betaalpha or p55alpha) subunit. |
| 5695 | 20348923 | Thus, p85alphaalpha forms a previously unrecognized link between the PI3K pathway, which is central to insulin action, and the regulation of the cellular response to ER stress, a state that when unresolved leads to insulin resistance. |
| 5696 | 20354339 | Physiologic implications of phosphoinositides and phospholipase C in the regulation of insulin secretion. |
| 5697 | 20354339 | These events include the cation calcium, which gains access to the beta-cell via the opening of voltage-regulated channels, cAMP and phosphoinositide-derived second messenger molecules, generated as a consequence of phospholipase C (PLC) activation. |
| 5698 | 20354339 | In this review, we focused on phosphoinositides, PLC/Phosphokinase C (PKC) and phosphatidylinositol 3-kinase (PI3K) cascade in the regulation of insulin secretion. |
| 5699 | 20354339 | We suggested that the failure of PLC activation can be attributed in the impairment of insulin secretion by chronic sustained glucose exposure. |
| 5700 | 20356977 | Abundance of FAS was higher in malignant cells than in non-malignant cells, and was up-regulated by IGF1 in both cell types. |
| 5701 | 20356977 | However, when the phosphatidylinositol 3-kinase pathway was inhibited, oleate enhanced IGF1-induced growth in both cell types. |
| 5702 | 20368287 | Interactome mapping of the phosphatidylinositol 3-kinase-mammalian target of rapamycin pathway identifies deformed epidermal autoregulatory factor-1 as a new glycogen synthase kinase-3 interactor. |
| 5703 | 20368287 | In particular, we identified the deformed epidermal autoregulatory factor-1 (DEAF1) transcription factor as an interactor and in vitro substrate of GSK3A and GSK3B. |
| 5704 | 20368287 | Moreover, GSK3 inhibitors increased DEAF1 transcriptional activity on the 5-HT1A serotonin receptor promoter. |
| 5705 | 20371624 | FOXO3a mediates signaling crosstalk that coordinates ubiquitin and atrogin-1/MAFbx expression during glucocorticoid-induced skeletal muscle atrophy. |
| 5706 | 20371624 | Muscle atrophy is a consequence of chronic diseases (e.g., diabetes) and glucocorticoid-induced insulin resistance that results from enhanced activity of the ubiquitin-proteasome pathway. |
| 5707 | 20371624 | The PI3K/Akt pathway inhibits the FOXO-mediated transcription of the muscle-specific E3 ligase atrogin-1/MAFbx (AT-1), whereas the MEK/ERK pathway increases Sp1 activity and ubiquitin (UbC) expression. |
| 5708 | 20371624 | We tested a signaling model in which FOXO3a mediates crosstalk between the PI3K/Akt and MEK/ERK pathways to coordinate AT-1 and UbC expression. |
| 5709 | 20371624 | In rat L6 myotubes, dexamethasone (> or = 24 h) reduced insulin receptor substrate (IRS)-1 protein and PI3K/Akt signaling and increased AT-1 mRNA. |
| 5710 | 20371624 | IRS-2 protein, MEK/ERK signaling, Sp1 phosphorylation, and UbC transcription were simultaneously increased. |
| 5711 | 20371624 | Knockdown of IRS-1 using small interfering RNA or adenovirus-mediated expression of constitutively activated FOXO3a increased IRS-2 protein, MEK/ERK signaling, and UbC expression. |
| 5712 | 20371624 | Changes in PI3K/Akt and MEK/ERK signaling were recapitulated in rat muscles undergoing atrophy due to streptozotocin-induced insulin deficiency and concurrently elevated glucocorticoid production. |
| 5713 | 20371624 | IRS-1 and Akt phosphorylation were decreased, whereas MEK/ERK signaling and expression of IRS-2, UbC and AT-1 were increased. |
| 5714 | 20371624 | We conclude that FOXO3a mediates a reciprocal communication between the IRS-1/PI3K/Akt and IRS-2/MEK/ERK pathways that coordinates AT-1 and ubiquitin expression during muscle atrophy. |
| 5715 | 20371624 | FOXO3a mediates signaling crosstalk that coordinates ubiquitin and atrogin-1/MAFbx expression during glucocorticoid-induced skeletal muscle atrophy. |
| 5716 | 20371624 | Muscle atrophy is a consequence of chronic diseases (e.g., diabetes) and glucocorticoid-induced insulin resistance that results from enhanced activity of the ubiquitin-proteasome pathway. |
| 5717 | 20371624 | The PI3K/Akt pathway inhibits the FOXO-mediated transcription of the muscle-specific E3 ligase atrogin-1/MAFbx (AT-1), whereas the MEK/ERK pathway increases Sp1 activity and ubiquitin (UbC) expression. |
| 5718 | 20371624 | We tested a signaling model in which FOXO3a mediates crosstalk between the PI3K/Akt and MEK/ERK pathways to coordinate AT-1 and UbC expression. |
| 5719 | 20371624 | In rat L6 myotubes, dexamethasone (> or = 24 h) reduced insulin receptor substrate (IRS)-1 protein and PI3K/Akt signaling and increased AT-1 mRNA. |
| 5720 | 20371624 | IRS-2 protein, MEK/ERK signaling, Sp1 phosphorylation, and UbC transcription were simultaneously increased. |
| 5721 | 20371624 | Knockdown of IRS-1 using small interfering RNA or adenovirus-mediated expression of constitutively activated FOXO3a increased IRS-2 protein, MEK/ERK signaling, and UbC expression. |
| 5722 | 20371624 | Changes in PI3K/Akt and MEK/ERK signaling were recapitulated in rat muscles undergoing atrophy due to streptozotocin-induced insulin deficiency and concurrently elevated glucocorticoid production. |
| 5723 | 20371624 | IRS-1 and Akt phosphorylation were decreased, whereas MEK/ERK signaling and expression of IRS-2, UbC and AT-1 were increased. |
| 5724 | 20371624 | We conclude that FOXO3a mediates a reciprocal communication between the IRS-1/PI3K/Akt and IRS-2/MEK/ERK pathways that coordinates AT-1 and ubiquitin expression during muscle atrophy. |
| 5725 | 20371624 | FOXO3a mediates signaling crosstalk that coordinates ubiquitin and atrogin-1/MAFbx expression during glucocorticoid-induced skeletal muscle atrophy. |
| 5726 | 20371624 | Muscle atrophy is a consequence of chronic diseases (e.g., diabetes) and glucocorticoid-induced insulin resistance that results from enhanced activity of the ubiquitin-proteasome pathway. |
| 5727 | 20371624 | The PI3K/Akt pathway inhibits the FOXO-mediated transcription of the muscle-specific E3 ligase atrogin-1/MAFbx (AT-1), whereas the MEK/ERK pathway increases Sp1 activity and ubiquitin (UbC) expression. |
| 5728 | 20371624 | We tested a signaling model in which FOXO3a mediates crosstalk between the PI3K/Akt and MEK/ERK pathways to coordinate AT-1 and UbC expression. |
| 5729 | 20371624 | In rat L6 myotubes, dexamethasone (> or = 24 h) reduced insulin receptor substrate (IRS)-1 protein and PI3K/Akt signaling and increased AT-1 mRNA. |
| 5730 | 20371624 | IRS-2 protein, MEK/ERK signaling, Sp1 phosphorylation, and UbC transcription were simultaneously increased. |
| 5731 | 20371624 | Knockdown of IRS-1 using small interfering RNA or adenovirus-mediated expression of constitutively activated FOXO3a increased IRS-2 protein, MEK/ERK signaling, and UbC expression. |
| 5732 | 20371624 | Changes in PI3K/Akt and MEK/ERK signaling were recapitulated in rat muscles undergoing atrophy due to streptozotocin-induced insulin deficiency and concurrently elevated glucocorticoid production. |
| 5733 | 20371624 | IRS-1 and Akt phosphorylation were decreased, whereas MEK/ERK signaling and expression of IRS-2, UbC and AT-1 were increased. |
| 5734 | 20371624 | We conclude that FOXO3a mediates a reciprocal communication between the IRS-1/PI3K/Akt and IRS-2/MEK/ERK pathways that coordinates AT-1 and ubiquitin expression during muscle atrophy. |
| 5735 | 20371624 | FOXO3a mediates signaling crosstalk that coordinates ubiquitin and atrogin-1/MAFbx expression during glucocorticoid-induced skeletal muscle atrophy. |
| 5736 | 20371624 | Muscle atrophy is a consequence of chronic diseases (e.g., diabetes) and glucocorticoid-induced insulin resistance that results from enhanced activity of the ubiquitin-proteasome pathway. |
| 5737 | 20371624 | The PI3K/Akt pathway inhibits the FOXO-mediated transcription of the muscle-specific E3 ligase atrogin-1/MAFbx (AT-1), whereas the MEK/ERK pathway increases Sp1 activity and ubiquitin (UbC) expression. |
| 5738 | 20371624 | We tested a signaling model in which FOXO3a mediates crosstalk between the PI3K/Akt and MEK/ERK pathways to coordinate AT-1 and UbC expression. |
| 5739 | 20371624 | In rat L6 myotubes, dexamethasone (> or = 24 h) reduced insulin receptor substrate (IRS)-1 protein and PI3K/Akt signaling and increased AT-1 mRNA. |
| 5740 | 20371624 | IRS-2 protein, MEK/ERK signaling, Sp1 phosphorylation, and UbC transcription were simultaneously increased. |
| 5741 | 20371624 | Knockdown of IRS-1 using small interfering RNA or adenovirus-mediated expression of constitutively activated FOXO3a increased IRS-2 protein, MEK/ERK signaling, and UbC expression. |
| 5742 | 20371624 | Changes in PI3K/Akt and MEK/ERK signaling were recapitulated in rat muscles undergoing atrophy due to streptozotocin-induced insulin deficiency and concurrently elevated glucocorticoid production. |
| 5743 | 20371624 | IRS-1 and Akt phosphorylation were decreased, whereas MEK/ERK signaling and expression of IRS-2, UbC and AT-1 were increased. |
| 5744 | 20371624 | We conclude that FOXO3a mediates a reciprocal communication between the IRS-1/PI3K/Akt and IRS-2/MEK/ERK pathways that coordinates AT-1 and ubiquitin expression during muscle atrophy. |
| 5745 | 20371624 | FOXO3a mediates signaling crosstalk that coordinates ubiquitin and atrogin-1/MAFbx expression during glucocorticoid-induced skeletal muscle atrophy. |
| 5746 | 20371624 | Muscle atrophy is a consequence of chronic diseases (e.g., diabetes) and glucocorticoid-induced insulin resistance that results from enhanced activity of the ubiquitin-proteasome pathway. |
| 5747 | 20371624 | The PI3K/Akt pathway inhibits the FOXO-mediated transcription of the muscle-specific E3 ligase atrogin-1/MAFbx (AT-1), whereas the MEK/ERK pathway increases Sp1 activity and ubiquitin (UbC) expression. |
| 5748 | 20371624 | We tested a signaling model in which FOXO3a mediates crosstalk between the PI3K/Akt and MEK/ERK pathways to coordinate AT-1 and UbC expression. |
| 5749 | 20371624 | In rat L6 myotubes, dexamethasone (> or = 24 h) reduced insulin receptor substrate (IRS)-1 protein and PI3K/Akt signaling and increased AT-1 mRNA. |
| 5750 | 20371624 | IRS-2 protein, MEK/ERK signaling, Sp1 phosphorylation, and UbC transcription were simultaneously increased. |
| 5751 | 20371624 | Knockdown of IRS-1 using small interfering RNA or adenovirus-mediated expression of constitutively activated FOXO3a increased IRS-2 protein, MEK/ERK signaling, and UbC expression. |
| 5752 | 20371624 | Changes in PI3K/Akt and MEK/ERK signaling were recapitulated in rat muscles undergoing atrophy due to streptozotocin-induced insulin deficiency and concurrently elevated glucocorticoid production. |
| 5753 | 20371624 | IRS-1 and Akt phosphorylation were decreased, whereas MEK/ERK signaling and expression of IRS-2, UbC and AT-1 were increased. |
| 5754 | 20371624 | We conclude that FOXO3a mediates a reciprocal communication between the IRS-1/PI3K/Akt and IRS-2/MEK/ERK pathways that coordinates AT-1 and ubiquitin expression during muscle atrophy. |
| 5755 | 20385725 | In this review, we will attempt to clarify the functions of these agents in in vitro differentiation strategies by focusing on the intracellular signaling pathways through which they operate - phosphatidylinositol 3-kinase, transforming growth factor beta, Wnt/beta-catenin, Hedgehog, and Notch. |
| 5756 | 20452396 | Incubation of HCAECs with exendin-4 resulted in a dose-dependent increase in DNA synthesis and an increased cell number, associated with an enhanced eNOS and Akt activation, which were inhibited by PKA, PI3K, Akt or eNOS inhibitors and abolished by a GLP-1 receptor antagonist. |
| 5757 | 20466847 | Glycogen synthase kinase 3 beta mediates high glucose-induced ubiquitination and proteasome degradation of insulin receptor substrate 1. |
| 5758 | 20466847 | Genetic and biological studies have shown that reductions in IRS1 and/or IRS2 protein levels are associated with insulin resistance. |
| 5759 | 20466847 | In this study we have shown that proteasome degradation of IRS1, but not of IRS2, is involved in HG-induced insulin resistance in Chinese hamster ovary (CHO) cells as well as in primary hepatocytes. |
| 5760 | 20466847 | To further investigate the molecular mechanism by which HG induces insulin resistance, we examined various molecular candidates with respect to their involvement in the reduction in IRS1 protein levels. |
| 5761 | 20466847 | In contrast to the insulin-induced degradation of IRS1, HG-induced degradation of IRS1 did not require IR signaling or phosphatidylinositol 3-kinase/Akt activity. |
| 5762 | 20466847 | We have identified glycogen synthase kinase 3beta (GSK3 beta or GSK3B as listed in the MGI Database) as a kinase required for HG-induced serine(332) phosphorylation, ubiquitination, and degradation of IRS1. |
| 5763 | 20466847 | Our data reveal the molecular mechanism of HG-induced insulin resistance, and support the notion that activation of GSK3 beta contributes to the induction of insulin resistance via phosphorylation of IRS1, triggering the ubiquitination and degradation of IRS1. |
| 5764 | 20512309 | Differential aetiology and impact of phosphoinositide 3-kinase (PI3K) and Akt signalling in skeletal muscle on in vivo insulin action. |
| 5765 | 20517721 | The Insulin Receptor/PI 3-kinase (INSR/PI3K) signalling pathway is a key regulator of cell and organismal metabolism. |
| 5766 | 20526383 | Phosphorylation of IRSs leads to activation of phosphatidylinositol 3-kinase (PI3K) and, subsequently, to activation of Akt and its downstream mediator AS160, all of which are important steps for stimulating glucose transport induced by insulin. |
| 5767 | 20526383 | Although the mechanisms underlying insulin resistance are not completely understood in skeletal muscle, it is thought to result, at least in part, from impaired insulin-dependent PI3K activation and downstream signaling. |
| 5768 | 20526383 | Phosphorylation of IRSs leads to activation of phosphatidylinositol 3-kinase (PI3K) and, subsequently, to activation of Akt and its downstream mediator AS160, all of which are important steps for stimulating glucose transport induced by insulin. |
| 5769 | 20526383 | Although the mechanisms underlying insulin resistance are not completely understood in skeletal muscle, it is thought to result, at least in part, from impaired insulin-dependent PI3K activation and downstream signaling. |
| 5770 | 20530665 | Phosphoinositide 3-kinase (PI3K) plays a critical role in tumorigenesis, and the PI3K p85 regulatory subunit exerts both positive and negative effects on signaling. |
| 5771 | 20530665 | Together, these results substantiate the concept that the p85 subunit of PI3K has a tumor-suppressive role in the liver and possibly other tissues. |
| 5772 | 20530665 | Phosphoinositide 3-kinase (PI3K) plays a critical role in tumorigenesis, and the PI3K p85 regulatory subunit exerts both positive and negative effects on signaling. |
| 5773 | 20530665 | Together, these results substantiate the concept that the p85 subunit of PI3K has a tumor-suppressive role in the liver and possibly other tissues. |
| 5774 | 20538496 | PTEN is an important control element of PI3K/AKT signaling involved in controlling the processes of embryonic development, cell migration and apoptosis. |
| 5775 | 20563709 | Most of the cellular responses to phosphatidylinositol 3-kinase activation and phosphatidylinositol 3,4,5-trisphosphate production are mediated by the activation of a group of AGC kinases comprising PKB, S6K, RSK, SGK and PKC isoforms, which play essential roles in regulating physiological processes related to cell growth, proliferation, survival and metabolism. |
| 5776 | 20570489 | EFAs and their metabolites activate phosphatidylinositol 3-kinase/murine thymoma viral oncogene homolog 1 (Akt) and p44/42 mitogen-activated protein kinases and stimulate gluconeogenesis and cell proliferation by Ca(2+), phospholipase C/protein kinase, events that are also necessary for stem cell proliferation. |
| 5777 | 20573722 | Glucagon secretion, insulin and IGF-IR autophosphorylation, and insulin receptor substrate (IRS)-1, IRS-2, phosphatidylinositol kinase (PI3K) (p85 alpha), and serine-threonine protein kinase (Akt) phosphorylated (active) forms were measured. |
| 5778 | 20573722 | Because MAPK can regulate Pax6, a transcription factor that controls glucagon expression, paired box gene 6 (Pax6) and glucagon gene and protein expression were also measured. |
| 5779 | 20573722 | Insulin-stimulated insulin receptor phosphorylation was greatly reduced by exposure to palmitate. |
| 5780 | 20573722 | Similar results were observed with IRS-1-P, PI3K (p85 alpha), and Akt-P. |
| 5781 | 20573722 | In these cells cultured, specifics MAPKs inhibitors were able to reduce both Pax6 and glucagon gene and protein expression. |
| 5782 | 20573722 | These results indicate that alpha-cells exposed to palmitate show insulin resistance of the IRS-1/PI3K/Akt pathway that likely controls glucagon secretion. |
| 5783 | 20573722 | In contrast, the IRS-2/MAPKs pathway is stimulated, through an activation of the IGF-IR, leading to increased Pax6 and glucagon expression. |
| 5784 | 20573722 | Glucagon secretion, insulin and IGF-IR autophosphorylation, and insulin receptor substrate (IRS)-1, IRS-2, phosphatidylinositol kinase (PI3K) (p85 alpha), and serine-threonine protein kinase (Akt) phosphorylated (active) forms were measured. |
| 5785 | 20573722 | Because MAPK can regulate Pax6, a transcription factor that controls glucagon expression, paired box gene 6 (Pax6) and glucagon gene and protein expression were also measured. |
| 5786 | 20573722 | Insulin-stimulated insulin receptor phosphorylation was greatly reduced by exposure to palmitate. |
| 5787 | 20573722 | Similar results were observed with IRS-1-P, PI3K (p85 alpha), and Akt-P. |
| 5788 | 20573722 | In these cells cultured, specifics MAPKs inhibitors were able to reduce both Pax6 and glucagon gene and protein expression. |
| 5789 | 20573722 | These results indicate that alpha-cells exposed to palmitate show insulin resistance of the IRS-1/PI3K/Akt pathway that likely controls glucagon secretion. |
| 5790 | 20573722 | In contrast, the IRS-2/MAPKs pathway is stimulated, through an activation of the IGF-IR, leading to increased Pax6 and glucagon expression. |
| 5791 | 20573722 | Glucagon secretion, insulin and IGF-IR autophosphorylation, and insulin receptor substrate (IRS)-1, IRS-2, phosphatidylinositol kinase (PI3K) (p85 alpha), and serine-threonine protein kinase (Akt) phosphorylated (active) forms were measured. |
| 5792 | 20573722 | Because MAPK can regulate Pax6, a transcription factor that controls glucagon expression, paired box gene 6 (Pax6) and glucagon gene and protein expression were also measured. |
| 5793 | 20573722 | Insulin-stimulated insulin receptor phosphorylation was greatly reduced by exposure to palmitate. |
| 5794 | 20573722 | Similar results were observed with IRS-1-P, PI3K (p85 alpha), and Akt-P. |
| 5795 | 20573722 | In these cells cultured, specifics MAPKs inhibitors were able to reduce both Pax6 and glucagon gene and protein expression. |
| 5796 | 20573722 | These results indicate that alpha-cells exposed to palmitate show insulin resistance of the IRS-1/PI3K/Akt pathway that likely controls glucagon secretion. |
| 5797 | 20573722 | In contrast, the IRS-2/MAPKs pathway is stimulated, through an activation of the IGF-IR, leading to increased Pax6 and glucagon expression. |
| 5798 | 20584641 | [Effects of exercise on expression and phosphorylation of PI3K and PKB in insulin signaling in the skeletal muscles of type 2 diabetic rats]. |
| 5799 | 20610572 | PDGF beta-receptor kinase activity and ERK1/2 mediate glycosaminoglycan elongation on biglycan and increases binding to LDL. |
| 5800 | 20610572 | Structural characteristics of glycosaminoglycan (GAG) chains on PGs influence lipoprotein binding and are altered adversely by platelet-derived growth factor (PDGF). |
| 5801 | 20610572 | The signaling pathway for PDGF-mediated GAG elongation via the PDGF receptor (PDGFR) was investigated. |
| 5802 | 20610572 | Knockdown of PDGFRbeta using small interfering RNA demonstrated that PDGF mediated changes in PGs via PDGFRbeta. |
| 5803 | 20610572 | Downstream signaling to GAG hyperelongation was mediated through ERK MAPK and not phosphatidylinositol-3 kinase or phospholipase Cgamma. |
| 5804 | 20610572 | In high-fat-fed apolipoprotein E(-/-) mice, inhibition of PDGFRbeta activity by imatinib reduced aortic total lipid staining area by 35% (P < 0.05). |
| 5805 | 20613712 | Phosphorylation of the H2A histone variant, H2AX, at the serine-139 residue, in the highly conserved C-terminal SQEY motif, forming gammaH2AX, is an early response to DNA double-strand breaks. |
| 5806 | 20613712 | This phosphorylation event is mediated by the phosphatidyl-inosito 3-kinase (PI3K) family of proteins, ataxia telangiectasia mutated (ATM), DNA-protein kinase catalytic subunit and ATM and RAD3-related (ATR). |
| 5807 | 20658573 | Since the insulin-stimulated antidiabetic activities of natural bioactive compounds are mediated by GLUT4 via the phosphatidylinositol-3-kinase (PI3K) and/or p38 mitogen activated protein kinase (p38-MAPK) pathway, the effects of pycnogenol were examined on the molecular mechanism of glucose uptake by the glucose transport system. 3T3-L1 adipocytes were treated with various concentrations of pycnogenol, and glucose uptake was examined using a non-radioisotope enzymatic assay and by molecular events associated with the glucose transport system using semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR). |
| 5808 | 20658573 | The results show that pycnogenol increased glucose uptake in fully differentiated 3T3-L1 adipocytes and increased the relative abundance of both GLUT4 and Akt mRNAs through the PI3K pathway in a dose dependent manner. |
| 5809 | 20658573 | Overall, these results indicate that pycnogenol may stimulate glucose uptake via the PI3K dependent tyrosine kinase pathways involving Akt. |
| 5810 | 20658573 | Since the insulin-stimulated antidiabetic activities of natural bioactive compounds are mediated by GLUT4 via the phosphatidylinositol-3-kinase (PI3K) and/or p38 mitogen activated protein kinase (p38-MAPK) pathway, the effects of pycnogenol were examined on the molecular mechanism of glucose uptake by the glucose transport system. 3T3-L1 adipocytes were treated with various concentrations of pycnogenol, and glucose uptake was examined using a non-radioisotope enzymatic assay and by molecular events associated with the glucose transport system using semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR). |
| 5811 | 20658573 | The results show that pycnogenol increased glucose uptake in fully differentiated 3T3-L1 adipocytes and increased the relative abundance of both GLUT4 and Akt mRNAs through the PI3K pathway in a dose dependent manner. |
| 5812 | 20658573 | Overall, these results indicate that pycnogenol may stimulate glucose uptake via the PI3K dependent tyrosine kinase pathways involving Akt. |
| 5813 | 20658573 | Since the insulin-stimulated antidiabetic activities of natural bioactive compounds are mediated by GLUT4 via the phosphatidylinositol-3-kinase (PI3K) and/or p38 mitogen activated protein kinase (p38-MAPK) pathway, the effects of pycnogenol were examined on the molecular mechanism of glucose uptake by the glucose transport system. 3T3-L1 adipocytes were treated with various concentrations of pycnogenol, and glucose uptake was examined using a non-radioisotope enzymatic assay and by molecular events associated with the glucose transport system using semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR). |
| 5814 | 20658573 | The results show that pycnogenol increased glucose uptake in fully differentiated 3T3-L1 adipocytes and increased the relative abundance of both GLUT4 and Akt mRNAs through the PI3K pathway in a dose dependent manner. |
| 5815 | 20658573 | Overall, these results indicate that pycnogenol may stimulate glucose uptake via the PI3K dependent tyrosine kinase pathways involving Akt. |
| 5816 | 20683642 | SOCS3 inhibits insulin signaling in porcine primary adipocytes. |
| 5817 | 20683642 | SOCS3 plays an important role in the development of insulin resistance. |
| 5818 | 20683642 | To investigate the role of SOCS3 in porcine adipocyte insulin signaling, we first detected the effect of insulin on SOCS3 mRNA and protein expression in porcine primary adipocytes by real-time RT-PCR and Western blotting. |
| 5819 | 20683642 | The results showed that 100 nM insulin could induce SOCS3 mRNA expression but not protein expression, and overexpression of SOCS3 decreased IRS1 protein level, insulin-stimulated IRS1 tyrosine phosphorylation, PI3K activation, and Akt phosphorylation, but increased IRS1 serine phosphorylation in porcine primary adipocytes. |
| 5820 | 20683642 | These results indicate that SOCS3 is an important negative regulator of insulin signaling in porcine adipocytes. |
| 5821 | 20683642 | Thus, SOCS3 may be a novel therapeutic target for the prevention or treatment of insulin resistance and type II diabetes. |
| 5822 | 20692412 | Compared with untreated cells the differentiation of human nonendocrine pancreatic cells into insulin-producing elements was increased after treatment with IGF-1, EGF, and Exendin-4, growth factors known to be activators of the PI3K pathway (12.2 +/- 3.2% vs 9.1 +/- 3.2%). |
| 5823 | 20692412 | Reverse transcriptase polymerase chain reaction (RT-PCR) analysis revealed that insulin-like growth factor-1 (IGF-1), epidermal growth factor (EGF), and Exendin-4 significantly increased the expression of the transcription factor neurogenin-3, whereas the expressions of pancreatic and duodenal homeobox 1 (PDX-1), neurogenic differentiation 1 (NeuroD) were increased only among samples treated with ZnCl2 and not significantly affected by treatment with the tested growth factors. |
| 5824 | 20692412 | Successful differentiation of IGF-1, EGF-, and Exendin-4-treated cells into functional beta cells was confirmed by C-peptide secretion in response to 5 versus 20 mmol glucose stimulation (0.24 vs 0.91 pmol C-peptide/microg DNA). |
| 5825 | 20692412 | These results showed that activation of the PI3K signaling pathway might be used to stimulate the differentiation of nonendocrine pancreatic cells into insulin-producing elements. |
| 5826 | 20692412 | Compared with untreated cells the differentiation of human nonendocrine pancreatic cells into insulin-producing elements was increased after treatment with IGF-1, EGF, and Exendin-4, growth factors known to be activators of the PI3K pathway (12.2 +/- 3.2% vs 9.1 +/- 3.2%). |
| 5827 | 20692412 | Reverse transcriptase polymerase chain reaction (RT-PCR) analysis revealed that insulin-like growth factor-1 (IGF-1), epidermal growth factor (EGF), and Exendin-4 significantly increased the expression of the transcription factor neurogenin-3, whereas the expressions of pancreatic and duodenal homeobox 1 (PDX-1), neurogenic differentiation 1 (NeuroD) were increased only among samples treated with ZnCl2 and not significantly affected by treatment with the tested growth factors. |
| 5828 | 20692412 | Successful differentiation of IGF-1, EGF-, and Exendin-4-treated cells into functional beta cells was confirmed by C-peptide secretion in response to 5 versus 20 mmol glucose stimulation (0.24 vs 0.91 pmol C-peptide/microg DNA). |
| 5829 | 20692412 | These results showed that activation of the PI3K signaling pathway might be used to stimulate the differentiation of nonendocrine pancreatic cells into insulin-producing elements. |
| 5830 | 20693566 | GIP increases human adipocyte LPL expression through CREB and TORC2-mediated trans-activation of the LPL gene. |
| 5831 | 20693566 | Additionally, emerging evidence suggests an important physiological role for GIP in the regulation of adipocyte metabolism. |
| 5832 | 20693566 | In previous studies on the lipogenic effects of GIP, it was shown to increase adipocyte lipoprotein lipase (LPL) activity in both differentiated 3T3-L1 cells and human adipocytes through a pathway involving activation of protein kinase B (PKB)/Akt. |
| 5833 | 20693566 | In the current study, we examined the effects of GIP on LPL gene expression. |
| 5834 | 20693566 | GIP in the presence of insulin increased LPL gene expression in human adipocytes and LPL promoter activity in GIP receptor-expressing HEK-293 cells, and both effects were greatly reduced by the transcription inhibitor actinomycin D. |
| 5835 | 20693566 | Subsequent studies established that GIP increased phosphorylation of Serine 133 in cAMP-response element binding protein (CREB) and the nuclear localization of cAMP-responsive CREB coactivator 2 (TORC2) through a pathway involving phosphatidylinositol 3-kinase (PI3-K), PKB, and AMP-activated protein kinase (AMPK). |
| 5836 | 20693566 | However, in the presence of insulin, GIP failed to activate the cAMP/PKA pathway. |
| 5837 | 20693566 | Knockdown of CREB and TORC2 using RNA interference reduced LPL expression, supporting a functional regulatory role. |
| 5838 | 20693566 | GIP-induced phospho-CREB and TORC2 were shown to bind to a cAMP-response element (-II) site in the human LPL promoter and GIP increased protein-protein interactions of these two factors. |
| 5839 | 20693566 | The lipogenic effects of GIP in the presence of insulin are therefore at least partially mediated by upregulation of adipocyte LPL gene transcription through a pathway involving PI3-K/PKB/AMPK-dependent CREB/TORC2 activation. |
| 5840 | 20693566 | GIP increases human adipocyte LPL expression through CREB and TORC2-mediated trans-activation of the LPL gene. |
| 5841 | 20693566 | Additionally, emerging evidence suggests an important physiological role for GIP in the regulation of adipocyte metabolism. |
| 5842 | 20693566 | In previous studies on the lipogenic effects of GIP, it was shown to increase adipocyte lipoprotein lipase (LPL) activity in both differentiated 3T3-L1 cells and human adipocytes through a pathway involving activation of protein kinase B (PKB)/Akt. |
| 5843 | 20693566 | In the current study, we examined the effects of GIP on LPL gene expression. |
| 5844 | 20693566 | GIP in the presence of insulin increased LPL gene expression in human adipocytes and LPL promoter activity in GIP receptor-expressing HEK-293 cells, and both effects were greatly reduced by the transcription inhibitor actinomycin D. |
| 5845 | 20693566 | Subsequent studies established that GIP increased phosphorylation of Serine 133 in cAMP-response element binding protein (CREB) and the nuclear localization of cAMP-responsive CREB coactivator 2 (TORC2) through a pathway involving phosphatidylinositol 3-kinase (PI3-K), PKB, and AMP-activated protein kinase (AMPK). |
| 5846 | 20693566 | However, in the presence of insulin, GIP failed to activate the cAMP/PKA pathway. |
| 5847 | 20693566 | Knockdown of CREB and TORC2 using RNA interference reduced LPL expression, supporting a functional regulatory role. |
| 5848 | 20693566 | GIP-induced phospho-CREB and TORC2 were shown to bind to a cAMP-response element (-II) site in the human LPL promoter and GIP increased protein-protein interactions of these two factors. |
| 5849 | 20693566 | The lipogenic effects of GIP in the presence of insulin are therefore at least partially mediated by upregulation of adipocyte LPL gene transcription through a pathway involving PI3-K/PKB/AMPK-dependent CREB/TORC2 activation. |
| 5850 | 20711845 | This effect is at least in part due to increase in the expression of proteins involved in the secretion process, and the activation of the PI3K/PKB/mTOR pathway seems also to contribute. |
| 5851 | 20714510 | Residues 762-801 of PLD1 mediate the interaction with PED/PEA15. |
| 5852 | 20714510 | The interaction of Phospholipase D1 (PLD1) by its C-terminal domain D4 with PED/PEA15 has been indicated as a target for type 2 diabetes. |
| 5853 | 20714510 | PED/PEA15 is overexpressed in several tissues of individuals affected by type 2 diabetes and its overexpression in intact cells and in transgenic animal models impairs insulin regulation of glucose transport by a mechanism mediated by the interaction with D4 and the consequent increase of protein kinase C-alpha activity. |
| 5854 | 20714510 | Expression of D4 or administration of a peptide mimicking the PED/PEA15 region involved in this interaction to cells stably overexpressing PED/PEA15 reduces its interaction with PLD1, thereby lowering PKC-alpha activation and restoring normal glucose transport mediated by PKC-zeta. |
| 5855 | 20714510 | By using D4 deletion mutants, we have restricted the PLD1 region involved in PED/PEA15 interaction to an N-terminal fragment named D4alpha (residues 712-818). |
| 5856 | 20714510 | This region binds PED/PEA15 with the same efficacy as D4 (K(D) approximately 0.7 microM) and, when transfected in different PED/PEA15-overexpressing cells, it is able to reduce PKC-alpha activity and to restore the sensitivity of PKC-zeta to insulin stimulation, independently of the PI3K/Akt signalling. |
| 5857 | 20714510 | We also show that the effective disruption of the PED/PEA15-PLD1 interaction can restore the normal ERK1/2 signalling. |
| 5858 | 20714879 | Analysis of phosphatidylinositol 3-kinase activation in the adipose tissue of gestational diabetes mellitus patients and insulin resistance. |
| 5859 | 20714879 | The P85 regulatory subunit protein and gene expression and P110 catalylic subunit activity of phosphatidylinositol 3-kinase (PI-3K) were investigated in adipose tissue of patients with gestational diabetes mellitus (GDM) in order to explore the molecular mechanisms of insulin resistance (IR) of GDM. |
| 5860 | 20714879 | Western blot technique was used to detect the levels of PI-3K P85 subunit in adipose tissues of patients with GDM. |
| 5861 | 20714879 | The mRNA expression of PI-3K P85 subunit was detected by reverse transcription polymerase chain reaction (RT-PCR) method in the adipose tissue. |
| 5862 | 20714879 | There was no significant difference in the protein and gene expression of PI-3K P85 subunit between GDM group and control group (P>0.05). |
| 5863 | 20714879 | It was concluded that PI-3K in GDM patients may be involved in the insulin signaling pathway, resulting in IR of GDM. |
| 5864 | 20714879 | Analysis of phosphatidylinositol 3-kinase activation in the adipose tissue of gestational diabetes mellitus patients and insulin resistance. |
| 5865 | 20714879 | The P85 regulatory subunit protein and gene expression and P110 catalylic subunit activity of phosphatidylinositol 3-kinase (PI-3K) were investigated in adipose tissue of patients with gestational diabetes mellitus (GDM) in order to explore the molecular mechanisms of insulin resistance (IR) of GDM. |
| 5866 | 20714879 | Western blot technique was used to detect the levels of PI-3K P85 subunit in adipose tissues of patients with GDM. |
| 5867 | 20714879 | The mRNA expression of PI-3K P85 subunit was detected by reverse transcription polymerase chain reaction (RT-PCR) method in the adipose tissue. |
| 5868 | 20714879 | There was no significant difference in the protein and gene expression of PI-3K P85 subunit between GDM group and control group (P>0.05). |
| 5869 | 20714879 | It was concluded that PI-3K in GDM patients may be involved in the insulin signaling pathway, resulting in IR of GDM. |
| 5870 | 20714879 | Analysis of phosphatidylinositol 3-kinase activation in the adipose tissue of gestational diabetes mellitus patients and insulin resistance. |
| 5871 | 20714879 | The P85 regulatory subunit protein and gene expression and P110 catalylic subunit activity of phosphatidylinositol 3-kinase (PI-3K) were investigated in adipose tissue of patients with gestational diabetes mellitus (GDM) in order to explore the molecular mechanisms of insulin resistance (IR) of GDM. |
| 5872 | 20714879 | Western blot technique was used to detect the levels of PI-3K P85 subunit in adipose tissues of patients with GDM. |
| 5873 | 20714879 | The mRNA expression of PI-3K P85 subunit was detected by reverse transcription polymerase chain reaction (RT-PCR) method in the adipose tissue. |
| 5874 | 20714879 | There was no significant difference in the protein and gene expression of PI-3K P85 subunit between GDM group and control group (P>0.05). |
| 5875 | 20714879 | It was concluded that PI-3K in GDM patients may be involved in the insulin signaling pathway, resulting in IR of GDM. |
| 5876 | 20714879 | Analysis of phosphatidylinositol 3-kinase activation in the adipose tissue of gestational diabetes mellitus patients and insulin resistance. |
| 5877 | 20714879 | The P85 regulatory subunit protein and gene expression and P110 catalylic subunit activity of phosphatidylinositol 3-kinase (PI-3K) were investigated in adipose tissue of patients with gestational diabetes mellitus (GDM) in order to explore the molecular mechanisms of insulin resistance (IR) of GDM. |
| 5878 | 20714879 | Western blot technique was used to detect the levels of PI-3K P85 subunit in adipose tissues of patients with GDM. |
| 5879 | 20714879 | The mRNA expression of PI-3K P85 subunit was detected by reverse transcription polymerase chain reaction (RT-PCR) method in the adipose tissue. |
| 5880 | 20714879 | There was no significant difference in the protein and gene expression of PI-3K P85 subunit between GDM group and control group (P>0.05). |
| 5881 | 20714879 | It was concluded that PI-3K in GDM patients may be involved in the insulin signaling pathway, resulting in IR of GDM. |
| 5882 | 20714879 | Analysis of phosphatidylinositol 3-kinase activation in the adipose tissue of gestational diabetes mellitus patients and insulin resistance. |
| 5883 | 20714879 | The P85 regulatory subunit protein and gene expression and P110 catalylic subunit activity of phosphatidylinositol 3-kinase (PI-3K) were investigated in adipose tissue of patients with gestational diabetes mellitus (GDM) in order to explore the molecular mechanisms of insulin resistance (IR) of GDM. |
| 5884 | 20714879 | Western blot technique was used to detect the levels of PI-3K P85 subunit in adipose tissues of patients with GDM. |
| 5885 | 20714879 | The mRNA expression of PI-3K P85 subunit was detected by reverse transcription polymerase chain reaction (RT-PCR) method in the adipose tissue. |
| 5886 | 20714879 | There was no significant difference in the protein and gene expression of PI-3K P85 subunit between GDM group and control group (P>0.05). |
| 5887 | 20714879 | It was concluded that PI-3K in GDM patients may be involved in the insulin signaling pathway, resulting in IR of GDM. |
| 5888 | 20714879 | Analysis of phosphatidylinositol 3-kinase activation in the adipose tissue of gestational diabetes mellitus patients and insulin resistance. |
| 5889 | 20714879 | The P85 regulatory subunit protein and gene expression and P110 catalylic subunit activity of phosphatidylinositol 3-kinase (PI-3K) were investigated in adipose tissue of patients with gestational diabetes mellitus (GDM) in order to explore the molecular mechanisms of insulin resistance (IR) of GDM. |
| 5890 | 20714879 | Western blot technique was used to detect the levels of PI-3K P85 subunit in adipose tissues of patients with GDM. |
| 5891 | 20714879 | The mRNA expression of PI-3K P85 subunit was detected by reverse transcription polymerase chain reaction (RT-PCR) method in the adipose tissue. |
| 5892 | 20714879 | There was no significant difference in the protein and gene expression of PI-3K P85 subunit between GDM group and control group (P>0.05). |
| 5893 | 20714879 | It was concluded that PI-3K in GDM patients may be involved in the insulin signaling pathway, resulting in IR of GDM. |
| 5894 | 20733001 | Insulin regulates adipocyte lipolysis via an Akt-independent signaling pathway. |
| 5895 | 20733001 | After a meal, insulin suppresses lipolysis through the activation of its downstream kinase, Akt, resulting in the inhibition of protein kinase A (PKA), the main positive effector of lipolysis. |
| 5896 | 20733001 | Here, we describe a noncanonical Akt-independent, phosphoinositide-3 kinase (PI3K)-dependent pathway that regulates adipocyte lipolysis using restricted subcellular signaling. |
| 5897 | 20733001 | In contrast, the phosphorylation of another PKA substrate, hormone-sensitive lipase (HSL), remains Akt dependent. |
| 5898 | 20802235 | Tropomyosin-related kinase (Trk) C, a member of the Trk family of neurotrophin receptors, has been implicated in the growth and survival of human cancer tissues. |
| 5899 | 20802235 | Ectopic expression of TrkC in non-malignant mammary epithelial cells suppressed anoikis, which correlated with activation of the Ras-mitogen-activated protein kinase and phosphatidylinositol-3-OH kinase (PI3K)/Akt pathways, and reduced expression of the metastatic regulator Twist. |
| 5900 | 20807190 | Recent data suggest that insulin resistance is directly implicated in atherosclerosis/restenosis, because of the unresponsiveness to the vasculoprotective action of insulin, including its phosphoinositide 3-kinase (PI3K)-Akt-endothelial nitric oxide synthase mediated enhancement of endothelial function. |
| 5901 | 20807190 | These 'atherogenic' actions are less affected by insulin resistance, which mainly involves the PI3K pathway. |
| 5902 | 20807190 | Recent data suggest that insulin resistance is directly implicated in atherosclerosis/restenosis, because of the unresponsiveness to the vasculoprotective action of insulin, including its phosphoinositide 3-kinase (PI3K)-Akt-endothelial nitric oxide synthase mediated enhancement of endothelial function. |
| 5903 | 20807190 | These 'atherogenic' actions are less affected by insulin resistance, which mainly involves the PI3K pathway. |
| 5904 | 20816670 | On molecular assay, 8-OHdG antagonized the action of GTP on Rac, a small GTP binding protein, without affecting Rac-guanosine exchange factor (GEF) or phosphoinositide 3-kinases (PI3K) activity. |
| 5905 | 20816670 | In Raw264.7 cells, 8-OHdG was found to be associated with marked attenuations of NOX1, NOXO1, and NOXA1 accompanied with the decreased expressions of LPS-induced inflammatory mediators including COX-2, iNOS, IL-1β, and IL-6. |
| 5906 | 20816670 | Similarly, 8-OHdG attenuated hypoxia-induced angiogenesis and platelet endothelial cell adhesion molecule-1 (PECAM-1), COX-2, iNOS, IL-8, and VEGF expressions in HUVEC cells. |
| 5907 | 20823563 | Moreover, 7-O-MA stimulated the reactivation of insulin-mediated phosphorylation of phosphatidylinositol 3-kinase (PI3K)-linked protein kinase B (Akt/PKB) and adenosine 5'-monophosphate-activated protein kinase (AMPK) in high glucose-induced, insulin-resistant HepG2 cells, and this effect was blocked by either LY294002, a PI3K inhibitor, or compound C, an AMPK inhibitor. |
| 5908 | 20823563 | Therefore, these results suggest that 7-O-MA might stimulate glucose uptake via PPARgamma2 activation and improve insulin resistance via PI3K and AMPK-dependent pathways, and be a potential candidate for the management of type 2 DM. |
| 5909 | 20823563 | Moreover, 7-O-MA stimulated the reactivation of insulin-mediated phosphorylation of phosphatidylinositol 3-kinase (PI3K)-linked protein kinase B (Akt/PKB) and adenosine 5'-monophosphate-activated protein kinase (AMPK) in high glucose-induced, insulin-resistant HepG2 cells, and this effect was blocked by either LY294002, a PI3K inhibitor, or compound C, an AMPK inhibitor. |
| 5910 | 20823563 | Therefore, these results suggest that 7-O-MA might stimulate glucose uptake via PPARgamma2 activation and improve insulin resistance via PI3K and AMPK-dependent pathways, and be a potential candidate for the management of type 2 DM. |
| 5911 | 20833210 | TGFβ1 treatment of HK-2 and RPTEC cells for 24h increased Jagged1 (a Notch ligand) and Hes1 (a Notch target) mRNA. |
| 5912 | 20833210 | In both cell types, TGFβ1-responsive genes associated with epithelial-mesenchymal transition such as E-cadherin and vimentin were also affected by γ-secretase inhibition, but other TGFβ1 targets such as connective tissue growth factor (CTGF) and thrombospondin-1 (THBS1) were not. |
| 5913 | 20833210 | TGFβ1-induced changes in Jagged1 expression preceded EMT-associated gene changes, and co-incubation with GSI altered TGFβ1-induced changes in cell shape and cytoskeleton. |
| 5914 | 20833210 | Increased Jagged1 expression upon TGFβ1 exposure required Smad3 signalling, and was also regulated by PI3K and ERK. |
| 5915 | 20833961 | Kinin B1 receptor upregulation by angiotensin II and endothelin-1 in rat vascular smooth muscle cells: receptors and mechanisms. |
| 5916 | 20833961 | Since angiotensin II (ANG II) and endothelin-1 (ET-1) are increased in these disorders, this study aims at determining the role of these two prooxidative peptides in B(1)R expression in rat vascular smooth muscle cells (VSMC). |
| 5917 | 20833961 | In A10 cells, ANG II (1 μM) also increased B(1)R mRNA expression at 3 h and the activation of induced B(1)R with the agonist [Sar-d-Phe(8)]-des-Arg(9)-BK (10 nM, 5 min) significantly enhanced mitogen-activated protein kinase (MAPK1/2) phosphorylation. |
| 5918 | 20833961 | The enhancing effect of ANG II on B(1)R protein expression in A10 cells was normalized by the AT(1) (losartan) but not by the AT(2) (PD123319) receptor antagonist. |
| 5919 | 20833961 | Furthermore, it was inhibited by inhibitors of phosphatidylinositol 3-kinase (wortmannin) and NF-κB (MG132) but not of MAPK (PD098059). |
| 5920 | 20833961 | The effect of ANG II is mediated by the AT(1) receptor and the subsequent activation of ET(A) through ET-1 release. |
| 5921 | 20872961 | The phosphoinositide 3-kinase (PI3K)/phosphatase and tensin homolog (PTEN)/Akt axis is a key signal transduction node that regulates crucial cellular functions, including insulin and other growth factors signaling, lipid and glucose metabolism, as well as cell survival and apoptosis. |
| 5922 | 20872961 | In this pathway, PTEN acts as a phosphoinositide phosphatase, which terminates PI3K-propagated signaling by dephosphorylating PtdIns(3,4)P(2) and PtdIns(3,4,5)P(3). |
| 5923 | 20872961 | However, the role of PTEN does not appear to be restricted only to PI3K signaling antagonism, and new functions have been recently discovered for this protein. |
| 5924 | 20872961 | Dysregulated PTEN expression/activity is observed with obesity, insulin resistance, diabetes, hepatitis B virus/hepatitis C virus infections, and abusive alcohol consumption, whereas mutations/deletions have also been associated with the occurrence of hepatocellular carcinoma. |
| 5925 | 20872961 | The phosphoinositide 3-kinase (PI3K)/phosphatase and tensin homolog (PTEN)/Akt axis is a key signal transduction node that regulates crucial cellular functions, including insulin and other growth factors signaling, lipid and glucose metabolism, as well as cell survival and apoptosis. |
| 5926 | 20872961 | In this pathway, PTEN acts as a phosphoinositide phosphatase, which terminates PI3K-propagated signaling by dephosphorylating PtdIns(3,4)P(2) and PtdIns(3,4,5)P(3). |
| 5927 | 20872961 | However, the role of PTEN does not appear to be restricted only to PI3K signaling antagonism, and new functions have been recently discovered for this protein. |
| 5928 | 20872961 | Dysregulated PTEN expression/activity is observed with obesity, insulin resistance, diabetes, hepatitis B virus/hepatitis C virus infections, and abusive alcohol consumption, whereas mutations/deletions have also been associated with the occurrence of hepatocellular carcinoma. |
| 5929 | 20872961 | The phosphoinositide 3-kinase (PI3K)/phosphatase and tensin homolog (PTEN)/Akt axis is a key signal transduction node that regulates crucial cellular functions, including insulin and other growth factors signaling, lipid and glucose metabolism, as well as cell survival and apoptosis. |
| 5930 | 20872961 | In this pathway, PTEN acts as a phosphoinositide phosphatase, which terminates PI3K-propagated signaling by dephosphorylating PtdIns(3,4)P(2) and PtdIns(3,4,5)P(3). |
| 5931 | 20872961 | However, the role of PTEN does not appear to be restricted only to PI3K signaling antagonism, and new functions have been recently discovered for this protein. |
| 5932 | 20872961 | Dysregulated PTEN expression/activity is observed with obesity, insulin resistance, diabetes, hepatitis B virus/hepatitis C virus infections, and abusive alcohol consumption, whereas mutations/deletions have also been associated with the occurrence of hepatocellular carcinoma. |
| 5933 | 20880397 | Effects of nominally selective inhibitors of the kinases PI3K, SGK1 and PKB on the insulin-dependent control of epithelial Na+ absorption. |
| 5934 | 20886413 | To examine its effect on insulin resistance, we treated high-glucose-induced, insulin-resistant HepG2 cells with scopoletin and measured phosphatidylinositol 3-kinase (PI3 K)-linked protein kinase B (Akt/PKB) phosphorylation. |
| 5935 | 20886413 | Scopoletin significantly stimulated the reactivation of insulin-mediated Akt/PKB phosphorylation. |
| 5936 | 20886413 | The ability of scopoletin to activate insulin-mediated Akt/PKB was greater than that of rosiglitazone, a thiazolidinedione, and scopoletin was less adipogenic than rosiglitazone, as shown by the extent of lipid accumulation in differentiated adipocytes. |
| 5937 | 20889126 | Examination of "normal" insulin-responsive podocytes in vivo and in vitro demonstrates that insulin signals through the MAPK and PI3K pathways via the insulin receptor and directly remodels the actin cytoskeleton of this cell. |
| 5938 | 20924498 | In addition, to the complexes the protein expression of AKT and PI3K were assayed. |
| 5939 | 20924498 | The expressions of PI3K and AKT also increased in the skeletal muscle. |
| 5940 | 20924498 | In addition, to the complexes the protein expression of AKT and PI3K were assayed. |
| 5941 | 20924498 | The expressions of PI3K and AKT also increased in the skeletal muscle. |
| 5942 | 20929506 | Cinnamic acid, from the bark of Cinnamomum cassia, regulates glucose transport via activation of GLUT4 on L6 myotubes in a phosphatidylinositol 3-kinase-independent manner. |
| 5943 | 20943662 | We found that tacrolimus decreased Akt phosphorylation, suggesting that calcineurin could regulate replication and survival via the PI3K/Akt pathway. |
| 5944 | 20943662 | We identify insulin receptor substrate-2 (Irs2), a known cAMP-responsive element-binding protein target and upstream regulator of the PI3K/Akt pathway, as a novel calcineurin target in β-cells. |
| 5945 | 20943662 | We found that tacrolimus decreased Akt phosphorylation, suggesting that calcineurin could regulate replication and survival via the PI3K/Akt pathway. |
| 5946 | 20943662 | We identify insulin receptor substrate-2 (Irs2), a known cAMP-responsive element-binding protein target and upstream regulator of the PI3K/Akt pathway, as a novel calcineurin target in β-cells. |
| 5947 | 20954077 | The 10% IS group, compared to control, showed that 15 genes including glucokinase (Gk-rs1) and LDL receptor relating protein 1 were upregulated and 12 genes including cell translocation gene2 (antiproliferative) and hydroxyprostaglandin dehydrogenase (Hpgd 15) were downregulated. |
| 5948 | 20954077 | With ML, Lepr (leptin receptor), Pik3cb (phosphatidylinositol 3-kinase), and Prodh (proline dehydrogenase), related to suppression of diabetes, were upregulated. |
| 5949 | 20954077 | In the case of SW, the enzymes (G2an, alpha glucosidase 2) and Mmp9 (matrix metalloproteinase 9) involved in elevation of blood glucose levels were both downregulated. |
| 5950 | 20954077 | Data suggest that I. sinclarii is effective in lowering blood glucose due to the upregulation of glucokinase (Gk-rs1) and downregulation of hydroxyprostaglandin dehydrogenase (Hpgd 15), both associated with suppression of diabetes, indicating that microarray analysis is a useful tool to assess pharmacological potency of therapeutic compounds. |
| 5951 | 20979575 | Compared with the subcutaneous arterioles of lean subjects, obesity activated the endothelium, enhanced the accumulation of collagen within vascular wall and increased the sensitivity of adrenergic response; obesity also diminished eNOS (endothelial NO synthase) protein expression, NO production, and endothelium-dependent and insulin-induced vasodilatation, as well as the protein expression of both IRS (insulin receptor substrates)-1 and IRS-2 and of the downstream molecules in the insulin signalling pathway, such as PI3K (phosphoinositide 3-kinase), phospho-Akt and Akt. |
| 5952 | 20979575 | In conclusion, obesity alone or obesity associated with Type 2 diabetes alters human periumbilical adipose tissue arterioles in terms of structure, function and biochemsitry, including diminished eNOS expression and reduced levels of IRS-1, IRS-2, PI3K and Akt in the insulin signalling pathway. |
| 5953 | 20979575 | Compared with the subcutaneous arterioles of lean subjects, obesity activated the endothelium, enhanced the accumulation of collagen within vascular wall and increased the sensitivity of adrenergic response; obesity also diminished eNOS (endothelial NO synthase) protein expression, NO production, and endothelium-dependent and insulin-induced vasodilatation, as well as the protein expression of both IRS (insulin receptor substrates)-1 and IRS-2 and of the downstream molecules in the insulin signalling pathway, such as PI3K (phosphoinositide 3-kinase), phospho-Akt and Akt. |
| 5954 | 20979575 | In conclusion, obesity alone or obesity associated with Type 2 diabetes alters human periumbilical adipose tissue arterioles in terms of structure, function and biochemsitry, including diminished eNOS expression and reduced levels of IRS-1, IRS-2, PI3K and Akt in the insulin signalling pathway. |
| 5955 | 21051417 | Moreover, insulin is the key component of glucose-insulin-potassium cocktail and exerts significant cardiovascular protective effect via a phosphatidylinositol 3'-kinase-protein kinase B-endothelial nitric oxide synthase (PI3K-Akt-eNOS)-dependent signalling mechanism in addition to its metabolic modulation, which renders it a potent organ protector in multiple clinical applications. |
| 5956 | 21051417 | This review focuses on insulin-initiated PI3K-Akt-eNOS survival signalling, with nitric oxide as an 'end effector' delivering cardioprotection in health and disease (especially in ischaemic heart disease), and highlights the impairment of this survival signalling as a key link between insulin resistance and cardiovascular disease. |
| 5957 | 21051417 | Moreover, insulin is the key component of glucose-insulin-potassium cocktail and exerts significant cardiovascular protective effect via a phosphatidylinositol 3'-kinase-protein kinase B-endothelial nitric oxide synthase (PI3K-Akt-eNOS)-dependent signalling mechanism in addition to its metabolic modulation, which renders it a potent organ protector in multiple clinical applications. |
| 5958 | 21051417 | This review focuses on insulin-initiated PI3K-Akt-eNOS survival signalling, with nitric oxide as an 'end effector' delivering cardioprotection in health and disease (especially in ischaemic heart disease), and highlights the impairment of this survival signalling as a key link between insulin resistance and cardiovascular disease. |
| 5959 | 21072680 | Over-expression of LYRM1 inhibits glucose transport in rat skeletal muscles via attenuated phosphorylation of PI3K (p85) and Akt. |
| 5960 | 21072680 | Western blotting was performed to assess the translocation of insulin-sensitive glucose transporter 4 (GLUT4). |
| 5961 | 21072680 | It was also used to measure the phosphorylation and total protein contents of insulin-signaling proteins, such as the insulin receptor (IR), insulin receptor substrate (IRS)-1, phosphatidylinositol-3-kinase (PI3K) p85, Akt, ERK1/2, P38, and JNK. |
| 5962 | 21072680 | LYRM1 over-expression in L6 myotubes reduced insulin-stimulated glucose uptake and impaired insulin-stimulated GLUT4 translocation. |
| 5963 | 21072680 | It also diminished insulin-stimulated tyrosine phosphorylation of IRS-1, PI3K (p85), and serine phosphorylation of Akt without affecting the phosphorylation of IR, ERK1/2, P38, and JNK. |
| 5964 | 21072680 | LYRM1 regulates the function of IRS-1, PI3K, and Akt, and decreases GLUT4 translocation and glucose uptake in response to insulin. |
| 5965 | 21072680 | Over-expression of LYRM1 inhibits glucose transport in rat skeletal muscles via attenuated phosphorylation of PI3K (p85) and Akt. |
| 5966 | 21072680 | Western blotting was performed to assess the translocation of insulin-sensitive glucose transporter 4 (GLUT4). |
| 5967 | 21072680 | It was also used to measure the phosphorylation and total protein contents of insulin-signaling proteins, such as the insulin receptor (IR), insulin receptor substrate (IRS)-1, phosphatidylinositol-3-kinase (PI3K) p85, Akt, ERK1/2, P38, and JNK. |
| 5968 | 21072680 | LYRM1 over-expression in L6 myotubes reduced insulin-stimulated glucose uptake and impaired insulin-stimulated GLUT4 translocation. |
| 5969 | 21072680 | It also diminished insulin-stimulated tyrosine phosphorylation of IRS-1, PI3K (p85), and serine phosphorylation of Akt without affecting the phosphorylation of IR, ERK1/2, P38, and JNK. |
| 5970 | 21072680 | LYRM1 regulates the function of IRS-1, PI3K, and Akt, and decreases GLUT4 translocation and glucose uptake in response to insulin. |
| 5971 | 21072680 | Over-expression of LYRM1 inhibits glucose transport in rat skeletal muscles via attenuated phosphorylation of PI3K (p85) and Akt. |
| 5972 | 21072680 | Western blotting was performed to assess the translocation of insulin-sensitive glucose transporter 4 (GLUT4). |
| 5973 | 21072680 | It was also used to measure the phosphorylation and total protein contents of insulin-signaling proteins, such as the insulin receptor (IR), insulin receptor substrate (IRS)-1, phosphatidylinositol-3-kinase (PI3K) p85, Akt, ERK1/2, P38, and JNK. |
| 5974 | 21072680 | LYRM1 over-expression in L6 myotubes reduced insulin-stimulated glucose uptake and impaired insulin-stimulated GLUT4 translocation. |
| 5975 | 21072680 | It also diminished insulin-stimulated tyrosine phosphorylation of IRS-1, PI3K (p85), and serine phosphorylation of Akt without affecting the phosphorylation of IR, ERK1/2, P38, and JNK. |
| 5976 | 21072680 | LYRM1 regulates the function of IRS-1, PI3K, and Akt, and decreases GLUT4 translocation and glucose uptake in response to insulin. |
| 5977 | 21072680 | Over-expression of LYRM1 inhibits glucose transport in rat skeletal muscles via attenuated phosphorylation of PI3K (p85) and Akt. |
| 5978 | 21072680 | Western blotting was performed to assess the translocation of insulin-sensitive glucose transporter 4 (GLUT4). |
| 5979 | 21072680 | It was also used to measure the phosphorylation and total protein contents of insulin-signaling proteins, such as the insulin receptor (IR), insulin receptor substrate (IRS)-1, phosphatidylinositol-3-kinase (PI3K) p85, Akt, ERK1/2, P38, and JNK. |
| 5980 | 21072680 | LYRM1 over-expression in L6 myotubes reduced insulin-stimulated glucose uptake and impaired insulin-stimulated GLUT4 translocation. |
| 5981 | 21072680 | It also diminished insulin-stimulated tyrosine phosphorylation of IRS-1, PI3K (p85), and serine phosphorylation of Akt without affecting the phosphorylation of IR, ERK1/2, P38, and JNK. |
| 5982 | 21072680 | LYRM1 regulates the function of IRS-1, PI3K, and Akt, and decreases GLUT4 translocation and glucose uptake in response to insulin. |
| 5983 | 21094196 | Ghrelin inhibits insulin resistance induced by glucotoxicity and lipotoxicity in cardiomyocyte. |
| 5984 | 21094196 | The aims of this study are to investigate the direct damage effect of high glucose and high palmitate on cardiomyocyte, and to study the effect of ghrelin on insulin resistance induced by glucotoxicity/lipotoxicity in cardiomyocyte and the possible mechanism underlying the cardioprotective activities of ghrelin. |
| 5985 | 21094196 | In addition, the phosphorylation of AKT occurred in 10min and was the highest in 30min after the stimulation with ghrelin, which can be blocked by phosphoinositide 3-kinase (PI3K) inhibitor, LY2940002. |
| 5986 | 21094196 | Ghrelin also increased the mRNA levels of glucose transporter 4 (GLUT4), peroxisome proliferators (PPARr) and AMP activated protein kinase (AMPK) genes in insulin signal transduction pathway. |
| 5987 | 21094196 | Ghrelin can inhibit gluco/lipotoxicity induced insulin resistance by PI3K/AKT pathway. |
| 5988 | 21094196 | Ghrelin inhibits insulin resistance induced by glucotoxicity and lipotoxicity in cardiomyocyte. |
| 5989 | 21094196 | The aims of this study are to investigate the direct damage effect of high glucose and high palmitate on cardiomyocyte, and to study the effect of ghrelin on insulin resistance induced by glucotoxicity/lipotoxicity in cardiomyocyte and the possible mechanism underlying the cardioprotective activities of ghrelin. |
| 5990 | 21094196 | In addition, the phosphorylation of AKT occurred in 10min and was the highest in 30min after the stimulation with ghrelin, which can be blocked by phosphoinositide 3-kinase (PI3K) inhibitor, LY2940002. |
| 5991 | 21094196 | Ghrelin also increased the mRNA levels of glucose transporter 4 (GLUT4), peroxisome proliferators (PPARr) and AMP activated protein kinase (AMPK) genes in insulin signal transduction pathway. |
| 5992 | 21094196 | Ghrelin can inhibit gluco/lipotoxicity induced insulin resistance by PI3K/AKT pathway. |
| 5993 | 21103795 | Many obesity-related factors are responsible, including increased blood levels of insulin/IGF, IL-6, TNF-alpha, and leptin, and decreased blood levels of adiponectin. |
| 5994 | 21103795 | IL-17 could activate Src/PI3K, MAPK, Stat3, and PKC, resulting in carcinogenesis. |
| 5995 | 21113666 | Ginsenoside Rb1 exerts cardioprotective effects against MI/R injury in diabetic rats, which is partly through activation of phosphatidylinositol 3-kinase (PI3 K)/Akt pathway. |
| 5996 | 21123564 | Leptin rapidly improves glucose homeostasis in obese mice by increasing hypothalamic insulin sensitivity. |
| 5997 | 21123564 | Obesity is associated with resistance to the actions of both leptin and insulin via mechanisms that remain incompletely understood. |
| 5998 | 21123564 | To investigate whether leptin resistance per se contributes to insulin resistance and impaired glucose homeostasis, we investigated the effect of acute leptin administration on glucose homeostasis in normal as well as leptin- or leptin receptor-deficient mice. |
| 5999 | 21123564 | In hyperglycemic, leptin-deficient Lep(ob/ob) mice, leptin acutely and potently improved glucose metabolism, before any change of body fat mass, via a mechanism involving the p110α and β isoforms of phosphatidylinositol-3-kinase (PI3K). |
| 6000 | 21123564 | Unlike insulin, however, the anti-diabetic effect of leptin occurred independently of phospho-AKT, a major downstream target of PI3K, and instead involved enhanced sensitivity of the hypothalamus to insulin action upstream of PI3K, through modulation of IRS1 (insulin receptor substrate 1) phosphorylation. |
| 6001 | 21123564 | These data suggest that leptin resistance, as occurs in obesity, reduces the hypothalamic response to insulin and thereby impairs peripheral glucose homeostasis, contributing to the development of type 2 diabetes. |
| 6002 | 21123564 | Leptin rapidly improves glucose homeostasis in obese mice by increasing hypothalamic insulin sensitivity. |
| 6003 | 21123564 | Obesity is associated with resistance to the actions of both leptin and insulin via mechanisms that remain incompletely understood. |
| 6004 | 21123564 | To investigate whether leptin resistance per se contributes to insulin resistance and impaired glucose homeostasis, we investigated the effect of acute leptin administration on glucose homeostasis in normal as well as leptin- or leptin receptor-deficient mice. |
| 6005 | 21123564 | In hyperglycemic, leptin-deficient Lep(ob/ob) mice, leptin acutely and potently improved glucose metabolism, before any change of body fat mass, via a mechanism involving the p110α and β isoforms of phosphatidylinositol-3-kinase (PI3K). |
| 6006 | 21123564 | Unlike insulin, however, the anti-diabetic effect of leptin occurred independently of phospho-AKT, a major downstream target of PI3K, and instead involved enhanced sensitivity of the hypothalamus to insulin action upstream of PI3K, through modulation of IRS1 (insulin receptor substrate 1) phosphorylation. |
| 6007 | 21123564 | These data suggest that leptin resistance, as occurs in obesity, reduces the hypothalamic response to insulin and thereby impairs peripheral glucose homeostasis, contributing to the development of type 2 diabetes. |
| 6008 | 21127054 | Phosphoinositide 3-kinases (PI3Ks) are critical regulators of pancreatic β cell mass and survival, whereas their involvement in insulin secretion is more controversial. |
| 6009 | 21127054 | Here we show that down-regulation of the class II PI3K isoform PI3K-C2α specifically impairs insulin granule exocytosis in rat insulinoma cells without affecting insulin content, the number of insulin granules at the plasma membrane, or the expression levels of key proteins involved in insulin secretion. |
| 6010 | 21127054 | Proteolysis of synaptosomal-associated protein of 25 kDa, a process involved in insulin granule exocytosis, is impaired in cells lacking PI3K-C2α. |
| 6011 | 21127054 | Phosphoinositide 3-kinases (PI3Ks) are critical regulators of pancreatic β cell mass and survival, whereas their involvement in insulin secretion is more controversial. |
| 6012 | 21127054 | Here we show that down-regulation of the class II PI3K isoform PI3K-C2α specifically impairs insulin granule exocytosis in rat insulinoma cells without affecting insulin content, the number of insulin granules at the plasma membrane, or the expression levels of key proteins involved in insulin secretion. |
| 6013 | 21127054 | Proteolysis of synaptosomal-associated protein of 25 kDa, a process involved in insulin granule exocytosis, is impaired in cells lacking PI3K-C2α. |
| 6014 | 21151615 | Shen-Fu injection preconditioning inhibits myocardial ischemia-reperfusion injury in diabetic rats: activation of eNOS via the PI3K/Akt pathway. |
| 6015 | 21151615 | SFI preconditioning significantly decreased infarct size, apoptosis, caspase-3 protein expression, MDA level in myocardial tissues, and plasma level of CK and LDH but increased p-Akt, p-eNOS, bcl-2 protein expression, and SOD activity compared to I/R group. |
| 6016 | 21153603 | ANG II type I receptor antagonism improved nitric oxide production and enhanced eNOS and PKB/Akt expression in hearts from a rat model of insulin resistance. |
| 6017 | 21153603 | Exogenous insulin therapy improves endothelial function in insulin resistant patients, indirectly indicating that nitric oxide synthase activity and NO production may be impaired. |
| 6018 | 21153603 | Insulin stimulates production of NO by activating a signaling pathway including insulin receptor substrate-1, phosphatidylinositol-3-kinase and protein kinase B (PKB/Akt). |
| 6019 | 21153603 | Angiotensin II type I (AT1) receptor-evoked oxidative stress is implicated in the inactivation of NO, impairing endothelium-dependent vasodilatation. |
| 6020 | 21153603 | Blocking the actions of Angiotensin II with an AT1 receptor antagonist (Losartan), has beneficial effects in patients with insulin resistance or type 2 diabetes mellitus. |
| 6021 | 21153603 | This study investigated whether elevated Angiotensin II influences myocardial insulin resistance, insulin signaling and NO production in a rat model of diet-induced obesity (DIO) by antagonizing the actions of the AT1 receptor with Losartan. |
| 6022 | 21153603 | Results showed that hearts from DIO rats are insulin resistant (higher serine phosphorylation of IRS-1, lower insulin-stimulated phosphorylation of PKB/Akt and eNOS, lower NO production) and had poorer functional recovery and larger infarct development after ischaemia/reperfusion. |
| 6023 | 21153603 | Data obtained from Losartan treatment also revealed that Angiotensin II signaling modulates myocardial PKB/Akt expression. |
| 6024 | 21153603 | We conclude that Angiotensin II signaling exacerbates inhibition of NO production in insulin resistance and that this can be improved by AT1 antagonism. |
| 6025 | 21170869 | It is activated by insulin and growth factors via phosphatidylinositol-3-kinase and the 3-phosphoinositide-dependent kinase PDK1. |
| 6026 | 21170869 | SGK1 enhances the activity of a variety of ion channels such as ENaC, TRPV5, ROMK, KCNE1/KCNQ1 and ClCKb; carriers such as NHE3, NKCC2, NCC and SGLT1; as well as the Na+/K+-ATPase. |
| 6027 | 21170869 | Thus, SGK1 may participate in the pathogenesis of metabolic syndrome or syndrome X, a condition characterized by the coincidence of essential hypertension, procoagulant state, obesity, insulin resistance and hyperinsulinemia. |
| 6028 | 21177833 | Integrin {alpha}3, but not {beta}1, regulates islet cell survival and function via PI3K/Akt signaling pathways. |
| 6029 | 21177833 | Previously, we have shown that human fetal islet and INS-1 cells highly express α3β1-integrin and that collagens I and IV significantly enhance their survival and function; in addition, blocking β1 function in the fetal islet cells decreased adhesion on collagen I and increased apoptosis. |
| 6030 | 21177833 | Perturbing α3 function in human islet or INS-1 cells resulted in significant decreases in cell function (adhesion, spreading, proliferation and Pdx1 and insulin expression/secretion), primarily on collagen IV. |
| 6031 | 21177833 | A significant decrease in focal adhesion kinase and ERK1/2 phosphorylation and increased caspase3 cleavage were observed on both collagens. |
| 6032 | 21177833 | Interestingly, only α3 blockade reduced expression of phospho-Akt and members of its downstream signaling cascades (glycogen synthase kinase β and X-linked inhibitor of apoptosis), demonstrating a specific effect of α3 on the phosphatidylinositol 3-kinase/Akt pathway. |
| 6033 | 21177833 | Integrin {alpha}3, but not {beta}1, regulates islet cell survival and function via PI3K/Akt signaling pathways. |
| 6034 | 21177833 | Previously, we have shown that human fetal islet and INS-1 cells highly express α3β1-integrin and that collagens I and IV significantly enhance their survival and function; in addition, blocking β1 function in the fetal islet cells decreased adhesion on collagen I and increased apoptosis. |
| 6035 | 21177833 | Perturbing α3 function in human islet or INS-1 cells resulted in significant decreases in cell function (adhesion, spreading, proliferation and Pdx1 and insulin expression/secretion), primarily on collagen IV. |
| 6036 | 21177833 | A significant decrease in focal adhesion kinase and ERK1/2 phosphorylation and increased caspase3 cleavage were observed on both collagens. |
| 6037 | 21177833 | Interestingly, only α3 blockade reduced expression of phospho-Akt and members of its downstream signaling cascades (glycogen synthase kinase β and X-linked inhibitor of apoptosis), demonstrating a specific effect of α3 on the phosphatidylinositol 3-kinase/Akt pathway. |
| 6038 | 21177856 | Protein kinase A-alpha directly phosphorylates FoxO1 in vascular endothelial cells to regulate expression of vascular cellular adhesion molecule-1 mRNA. |
| 6039 | 21177856 | FoxO1, a forkhead box O class transcription factor, is abundant in insulin-responsive tissues. |
| 6040 | 21177856 | Akt, downstream from phosphatidylinositol 3-kinase in insulin signaling, phosphorylates FoxO1 at Thr(24), Ser(256), and Ser(319), negatively regulating its function. |
| 6041 | 21177856 | We previously reported that dehydroepiandrosterone-stimulated phosphorylation of FoxO1 in endothelial cells requires cAMP-dependent protein kinase α (PKA-α). |
| 6042 | 21177856 | Using an immune complex kinase assay with [γ-(32)P]ATP, purified PKA-α directly phosphorylated wild-type FoxO1 but not FoxO1-AAA (mutant with alanine substitutions at known Akt phosphorylation sites). |
| 6043 | 21186102 | Evidence has been reported that chemokine CXCL16, rather than CD36, is the main scavenger receptor in human podocytes mediating the uptake of ox-LDL. |
| 6044 | 21186102 | It has been recently shown that nephrin once phosphorilated associates with PI3K and stimulates the Akt dependent signaling. |
| 6045 | 21186102 | Notably CXCL16 are the main receptors for the uptake of ox-LDL in podocytes, whereas CD36 plays this role in tubular renal cells. |
| 6046 | 21207218 | Treadmill exercise suppresses muscle cell apoptosis by increasing nerve growth factor levels and stimulating p-phosphatidylinositol 3-kinase activation in the soleus of diabetic rats. |
| 6047 | 21207218 | We investigated the effects of treadmill exercise performed regularly for 6 weeks on the levels of nerve growth factor (NGF), tyrosine kinase A and p75 receptors, phosphatidylinositol 3-kinase (PI3-K), mitogen-activated protein kinase/extracellular signal-regulated kinase (Erk) 1,2, cyclic AMP response element-binding protein (CREB), and caspase-3 in the soleus of rats with streptozotocin (STZ)-induced diabetes. |
| 6048 | 21207218 | The protein level of NGF significantly increased in the NEG and DEG (p < 0.001), whereas the levels of tyrosine kinase A and p75 receptors significantly increased in the NEG (p < 0.001). |
| 6049 | 21207218 | Treadmill exercise suppresses muscle cell apoptosis by increasing nerve growth factor levels and stimulating p-phosphatidylinositol 3-kinase activation in the soleus of diabetic rats. |
| 6050 | 21207218 | We investigated the effects of treadmill exercise performed regularly for 6 weeks on the levels of nerve growth factor (NGF), tyrosine kinase A and p75 receptors, phosphatidylinositol 3-kinase (PI3-K), mitogen-activated protein kinase/extracellular signal-regulated kinase (Erk) 1,2, cyclic AMP response element-binding protein (CREB), and caspase-3 in the soleus of rats with streptozotocin (STZ)-induced diabetes. |
| 6051 | 21207218 | The protein level of NGF significantly increased in the NEG and DEG (p < 0.001), whereas the levels of tyrosine kinase A and p75 receptors significantly increased in the NEG (p < 0.001). |
| 6052 | 21234858 | Serine-1177-specific phosphorylation of NOS type 3 (NOS-3) and phosphorylation of protein kinase Akt were determined in platelets by Western blotting. |
| 6053 | 21234858 | Western blotting studies revealed that AGEs decreased NOS-3 phosphorylation on serine-1177, increased NOS-3 O-glycosylation, and decreased serine phosphorylation of protein kinase Akt; all of these changes were abrogated by pyridoxine. |
| 6054 | 21234858 | We conclude that pyridoxine is effective in ameliorating the dysfunction of platelet NO signaling in response to AGEs, through improving PI3K activity, and hence downstream Akt phosphorylation and in turn serine-1177 phosphorylation of NOS-3. |
| 6055 | 21289260 | Insulin- and leptin-mediated control of aquaglyceroporins in human adipocytes and hepatocytes is mediated via the PI3K/Akt/mTOR signaling cascade. |
| 6056 | 21304221 | After binding to its receptor and activating the β-subunit, insulin is faced with two divergent pathways: one is phosphatidylinositol 3-kinase (PI 3-K) dependent, while another is dependent upon activation of mitogen-activated protein kinase (MAP-K). |
| 6057 | 21304221 | In obese patients, especially with type 2 diabetes mellitus (DM2), only the PI 3-K, but not the MAP-K, is resistant to insulin stimulation: hence insulin resistance is better defined as metabolic insulin resistance. |
| 6058 | 21304221 | The resulting 'compensatory hyperinsulinemia' is an unsuccessful attempt to overcome the inhibition of the metabolic pathway at the price of unopposed stimulation of the MAP-K pathway, and the administration of exogenous insulin might worsen the metabolic dysfunction. |
| 6059 | 21304221 | As the preferential activation of the MAP-K pathway in insulin-resistant patients has atherogenic and mitogenic properties, this leads to atherosclerosis and cancer. |
| 6060 | 21305025 | The signaling mechanisms involved several proteins that include 7 major functional proteins such as INS, INSR, IRS1, IRS2, PIK3CA, Akt2, and GLUT4. |
| 6061 | 21321093 | We found levels of adiponectin, leptin, and TSHR mRNA to be increased in GO cultures treated for 10 days with either M22 (2.6 mean fold ± 0.7; P=0.03) or TSH (13.2 ± 5.8-fold, P=0.048). |
| 6062 | 21321093 | Inhibition of PI3K activity during 10 days in culture decreased the levels of M22-stimulated mRNA encoding adiponectin (67 ± 12%; P=0.021), as well as adiponectin and CCAAT/enhancer-binding protein α protein levels. |
| 6063 | 21335550 | FoxO1 activity is tightly controlled by phosphatidylinositol 3-kinase (PI3K) signaling, resulting in its phosphorylation and nuclear exclusion. |
| 6064 | 21335550 | We sought here to determine the mechanisms involved in glucose and insulin-stimulated nuclear shuttling of FoxO1 in pancreatic β cells and its consequences for preproinsulin (Ins1, Ins2) gene expression. |
| 6065 | 21335550 | Constitutively active PI3K or protein kinase B/Akt exerted similar effects, while inhibitors of PI3K, but not of glycogen synthase kinase-3 or p70 S6 kinase, blocked nuclear export. |
| 6066 | 21335550 | FoxO1 overexpression reversed the activation by glucose of pancreatic duodenum homeobox-1 (Pdx1) transcription. |
| 6067 | 21335550 | A 915-bp glucose-responsive Ins2 promoter was inhibited by constitutively active FoxO1, an effect unaltered by simultaneous overexpression of PDX1. |
| 6068 | 21335550 | We conclude that nuclear import of FoxO1 contributes to the suppression of Pdx1 and Ins2 gene expression at low glucose, the latter via a previously unsuspected and direct physical interaction with the Ins2 promoter. |
| 6069 | 21335550 | FoxO1 activity is tightly controlled by phosphatidylinositol 3-kinase (PI3K) signaling, resulting in its phosphorylation and nuclear exclusion. |
| 6070 | 21335550 | We sought here to determine the mechanisms involved in glucose and insulin-stimulated nuclear shuttling of FoxO1 in pancreatic β cells and its consequences for preproinsulin (Ins1, Ins2) gene expression. |
| 6071 | 21335550 | Constitutively active PI3K or protein kinase B/Akt exerted similar effects, while inhibitors of PI3K, but not of glycogen synthase kinase-3 or p70 S6 kinase, blocked nuclear export. |
| 6072 | 21335550 | FoxO1 overexpression reversed the activation by glucose of pancreatic duodenum homeobox-1 (Pdx1) transcription. |
| 6073 | 21335550 | A 915-bp glucose-responsive Ins2 promoter was inhibited by constitutively active FoxO1, an effect unaltered by simultaneous overexpression of PDX1. |
| 6074 | 21335550 | We conclude that nuclear import of FoxO1 contributes to the suppression of Pdx1 and Ins2 gene expression at low glucose, the latter via a previously unsuspected and direct physical interaction with the Ins2 promoter. |
| 6075 | 21347618 | To clarify the mechanisms underlying this cardioprotection, we explored Epo treatment of coronary artery endothelial cells and Epo cardioprotection in a Mus musculus model with Epo receptor expression restricted to hematopoietic and endothelial cells (ΔEpoR). |
| 6076 | 21347618 | Epo stimulation of coronary artery endothelial cells upregulated endothelial nitric oxide synthase (eNOS) activity in vitro and in vivo, and enhanced nitric oxide (NO) production that was determined directly by real-time measurements of gaseous NO release. |
| 6077 | 21347618 | Epo stimulated phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) and mitogen-activated protein kinase kinase (MEK)/extracellular signal regulated kinase (ERK) signaling pathways, and inhibition of PI3K, but not MEK activity, blocked Epo-induced NO production. |
| 6078 | 21368653 | Diabetes blockade of sevoflurane postconditioning is not restored by insulin in the rat heart: phosphorylated signal transducer and activator of transcription 3- and phosphatidylinositol 3-kinase-mediated inhibition. |
| 6079 | 21372207 | Mesangial cells in diabetic mice and human kidneys with diabetic nephropathy exhibit increased type VIII collagen, a nonfibrillar protein that exists as a heterodimer composed of α1(VIII) and α2(VIII), encoded by Col8a1 and Col8a2, respectively. |
| 6080 | 21372207 | We obtained primary cultures of mesangial cells from wild-type, doubly heterozygous (Col8a1(+/-)/Col8a2(+/-)), and double-knockout (Col8a1(-/-)/Col8a2(-/-)) mice. |
| 6081 | 21372207 | Furthermore, in wild-type cells, TGF-β1 mainly stimulated the Smad pathways, whereas in double-knockout cells, it activated the MAPK and PI3K/Akt pathways and induced expression of fibroblast growth factor 21 (FGF21). |
| 6082 | 21372207 | Inhibiting FGF21 expression by either interfering with activation of the MAPK and PI3K/Akt pathways or by FGF21 siRNA attenuated the TGF-β1-induced proliferation of double-knockout mesangial cells. |
| 6083 | 21372207 | Mesangial cells in diabetic mice and human kidneys with diabetic nephropathy exhibit increased type VIII collagen, a nonfibrillar protein that exists as a heterodimer composed of α1(VIII) and α2(VIII), encoded by Col8a1 and Col8a2, respectively. |
| 6084 | 21372207 | We obtained primary cultures of mesangial cells from wild-type, doubly heterozygous (Col8a1(+/-)/Col8a2(+/-)), and double-knockout (Col8a1(-/-)/Col8a2(-/-)) mice. |
| 6085 | 21372207 | Furthermore, in wild-type cells, TGF-β1 mainly stimulated the Smad pathways, whereas in double-knockout cells, it activated the MAPK and PI3K/Akt pathways and induced expression of fibroblast growth factor 21 (FGF21). |
| 6086 | 21372207 | Inhibiting FGF21 expression by either interfering with activation of the MAPK and PI3K/Akt pathways or by FGF21 siRNA attenuated the TGF-β1-induced proliferation of double-knockout mesangial cells. |
| 6087 | 21376236 | Active mTORC2 was physically associated with the ribosome, and insulin-stimulated PI3K signaling promoted mTORC2-ribosome binding, suggesting that ribosomes activate mTORC2 directly. |
| 6088 | 21382660 | These studies have provided evidence that carnosol targets multiple deregulated pathways associated with inflammation and cancer that include nuclear factor kappa B (NFκB), apoptotic related proteins, phosphatidylinositol-3-kinase (PI3 K)/Akt, androgen and estrogen receptors, as well as molecular targets. |
| 6089 | 21416924 | Estrogen could regulate the expressions of anorexia and hyperphagic neuropeptide in the hypothalamus by genomic actions via nuclear ER, or via membrane ER linking to the phosphatidylinositol 3-kinase (PI3-K)/Akt and ERK1/2 mitogen-activated protein kinase (MAPK) pathways. |
| 6090 | 21416924 | Further studies showed that the central ERalpha interacts with both insulin and leptin signaling pathways. |
| 6091 | 21475143 | Examined were the effects of intravenously infused glucose and/or lipids on proximal ER stress sensor activation (PERK, eIF2-α, ATF4, Xbox protein 1 (XBP1s)), unfolded protein response (UPR) proteins (GRP78, calnexin, calreticulin, protein disulphide isomerase (PDI), stress kinases (JNK, p38 MAPK) and insulin signaling (insulin/receptor substrate (IRS) 1/2 associated phosphoinositol-3-kinase (PI3K)) in rat liver. |
| 6092 | 21475143 | Glucose and/or lipid infusions, ranging from 23.8 to 69.5 kJ/4 h (equivalent to between ~17% and ~50% of normal daily energy intake), activated the proximal ER stress sensor PERK and ATF6 increased the protein abundance of calnexin, calreticulin and PDI and increased two GRP78 isoforms. |
| 6093 | 21475143 | Glucose and glucose plus lipid infusions induced comparable degrees of ER stress, but only infusions containing lipid activated stress kinases (JNK and p38 MAPK) and inhibited insulin signaling (PI3K). |
| 6094 | 21475143 | Examined were the effects of intravenously infused glucose and/or lipids on proximal ER stress sensor activation (PERK, eIF2-α, ATF4, Xbox protein 1 (XBP1s)), unfolded protein response (UPR) proteins (GRP78, calnexin, calreticulin, protein disulphide isomerase (PDI), stress kinases (JNK, p38 MAPK) and insulin signaling (insulin/receptor substrate (IRS) 1/2 associated phosphoinositol-3-kinase (PI3K)) in rat liver. |
| 6095 | 21475143 | Glucose and/or lipid infusions, ranging from 23.8 to 69.5 kJ/4 h (equivalent to between ~17% and ~50% of normal daily energy intake), activated the proximal ER stress sensor PERK and ATF6 increased the protein abundance of calnexin, calreticulin and PDI and increased two GRP78 isoforms. |
| 6096 | 21475143 | Glucose and glucose plus lipid infusions induced comparable degrees of ER stress, but only infusions containing lipid activated stress kinases (JNK and p38 MAPK) and inhibited insulin signaling (PI3K). |
| 6097 | 21478266 | TGF-β1/ALK5-induced monocyte migration involves PI3K and p38 pathways and is not negatively affected by diabetes mellitus. |
| 6098 | 21484150 | The expression of protein kinase B (Akt), glucose transporter 4 (GLUT4), hormone sensitive lipase (HSL), and phosphatidylinositol-3-kinase (PI3 K) genes in SIT-treated adipocytes were assessed by real-time reverse transcription polymerase chain reaction (RT-PCR). |
| 6099 | 21484150 | Interestingly, although SIT displayed general insulin-mimetic activity by stimulating glucose uptake and adipogenesis, it also induced lipolysis in adipocytes. |
| 6100 | 21484150 | Furthermore, the SIT-induced lipolysis was not attenuated by insulin and co-incubation of SIT with epinephrine improved epinephrine-induced lipolysis. |
| 6101 | 21484150 | GLUT4 gene expression was highly down-regulated in SIT-treated adipocytes, compared to insulin-treated adipocytes, which was up-regulated. |
| 6102 | 21484150 | Insulin- and SIT-treated adipocytes showed similar levels of Akt, HSL, and PI3 K gene down-regulation. |
| 6103 | 21484150 | These observations suggest that the elevation of glucose uptake in SIT-treated adipocytes was unrelated to de novo synthesis of GLUT4 and the SIT-induced lipolysis is associated with the down-regulation of Akt and PI3K genes. |
| 6104 | 21484150 | The expression of protein kinase B (Akt), glucose transporter 4 (GLUT4), hormone sensitive lipase (HSL), and phosphatidylinositol-3-kinase (PI3 K) genes in SIT-treated adipocytes were assessed by real-time reverse transcription polymerase chain reaction (RT-PCR). |
| 6105 | 21484150 | Interestingly, although SIT displayed general insulin-mimetic activity by stimulating glucose uptake and adipogenesis, it also induced lipolysis in adipocytes. |
| 6106 | 21484150 | Furthermore, the SIT-induced lipolysis was not attenuated by insulin and co-incubation of SIT with epinephrine improved epinephrine-induced lipolysis. |
| 6107 | 21484150 | GLUT4 gene expression was highly down-regulated in SIT-treated adipocytes, compared to insulin-treated adipocytes, which was up-regulated. |
| 6108 | 21484150 | Insulin- and SIT-treated adipocytes showed similar levels of Akt, HSL, and PI3 K gene down-regulation. |
| 6109 | 21484150 | These observations suggest that the elevation of glucose uptake in SIT-treated adipocytes was unrelated to de novo synthesis of GLUT4 and the SIT-induced lipolysis is associated with the down-regulation of Akt and PI3K genes. |
| 6110 | 21487310 | Intranasal delivery of insulin was associated with greater preservation of the phosphatidylinositol 3-kinase signaling pathway involving Akt, cyclic AMP response element binding protein,and glycogen synthase kinase 3β but did not alter extracellular signal-regulated kinase, mitogen-activated protein kinase/extracellular signal-regulated kinase, or c-Jun amino-terminal kinase. |
| 6111 | 21487310 | Thus, direct delivery of insulin to the nervous system might prevent motor deficit in human type 1 diabetes by preservation of the phosphatidylinositol 3-kinase-Akt pathway rather than only affecting glycemic levels; the effects of insulin on other signaling pathways may, however, play additional roles. |
| 6112 | 21487310 | Intranasal delivery of insulin was associated with greater preservation of the phosphatidylinositol 3-kinase signaling pathway involving Akt, cyclic AMP response element binding protein,and glycogen synthase kinase 3β but did not alter extracellular signal-regulated kinase, mitogen-activated protein kinase/extracellular signal-regulated kinase, or c-Jun amino-terminal kinase. |
| 6113 | 21487310 | Thus, direct delivery of insulin to the nervous system might prevent motor deficit in human type 1 diabetes by preservation of the phosphatidylinositol 3-kinase-Akt pathway rather than only affecting glycemic levels; the effects of insulin on other signaling pathways may, however, play additional roles. |
| 6114 | 21491265 | The molecular targets involved in chemoprevention like the inhibition of NF-κB activation via impairing nuclear translocation, suppresses cIAP1 expression, increases caspase-3/7 activation, arrests cell cycle in G2 + M phases, up-regulates Cytochrome-c, Apaf-1, activates PI3K/Akt/I kappaB kinases IKK, suppresses cell proliferation, and inducts apoptosis and chromatin condensation. |
| 6115 | 21491265 | Furthermore, inhibition of phosphorylation of three mitogen-activated protein kinases (MAPKs), extracellular signal-regulated kinases 1 and 2 (ERK1/2), and c-Jun N-terminal kinase (JNK) are also discussed. |
| 6116 | 21520470 | It was further confirmed in a series of experiments that ginsenosides Rg3 and Re stimulated the mRNA expression of insulin receptor substrate (IRS-1) and the expression of phosphatidylinositol 3-kinase (PI3K)-110α protein, which is involved in downstream events in the insulin signaling pathway. |
| 6117 | 21520470 | These findings demonstrate that ginsenosides Rg3 and Re may stimulate glucose uptake via the PI3K pathways involving IRS-1. |
| 6118 | 21520470 | It was further confirmed in a series of experiments that ginsenosides Rg3 and Re stimulated the mRNA expression of insulin receptor substrate (IRS-1) and the expression of phosphatidylinositol 3-kinase (PI3K)-110α protein, which is involved in downstream events in the insulin signaling pathway. |
| 6119 | 21520470 | These findings demonstrate that ginsenosides Rg3 and Re may stimulate glucose uptake via the PI3K pathways involving IRS-1. |
| 6120 | 21586696 | In cultured hepatocytes, we observed that expressions of ACSL1 and -5 were stimulated by insulin signaling. |
| 6121 | 21586696 | Results in cultured cells also showed that blunting insulin signaling by the PI3K inhibitor LY-294002 prevented fat accumulation, oxidative stress, and insulin resistance induced by the prolonged exposure to either insulin or oleate plus sera that normally contain insulin. |
| 6122 | 21600934 | Regulation of heparanase by albumin and advanced glycation end products in proximal tubular cells. |
| 6123 | 21600934 | Albumin and advanced glycation end-product, but not high glucose levels, increased heparanase expression in adult tubular cells via the AKT/PI3K signaling pathway. |
| 6124 | 21600934 | In fact, heparanase regulates the gene expression of syndecan-1, the most abundant heparan sulfate-proteoglycans in tubular cells. |
| 6125 | 21600934 | We showed that heparanase is a target gene of the diabetic nephropathy mediators albumin and advanced glycation end-product, so it may be relevant to the progression of diabetic nephropathy. |
| 6126 | 21600934 | It could take part in several processes, e.g. extracellular-matrix remodeling and cell-cell crosstalk, via its heparan sulfate endoglycosidase activity and capacity to regulate the expression of the heparan sulfate-proteoglycan syndecan-1. |
| 6127 | 21608432 | Effect of insulin in combination with selenium on blood glucose and PI3K-mediated GLUT4 expression in skeletal muscle of streptozotocin-induced diabetic rats. |
| 6128 | 21620963 | Erythropoietin protects retinal pigment epithelial cells against the increase of permeability induced by diabetic conditions: essential role of JAK2/ PI3K signaling. |
| 6129 | 21620963 | The experiments were repeated in the presence of an Epo neutralizing antibody and specific inhibitors of JAK2 and PI3K (AG490 and LY294002, respectively). |
| 6130 | 21620963 | Epo treatment was able to prevent but not to restore the increase of permeability induced by high glucose plus IL-1β. |
| 6131 | 21620963 | In addition, Epo was able to increase cytosolic Ca(2+) with dependence on extracellular calcium influx and this effect was blocked by either JAK2 or PI3K inhibition. |
| 6132 | 21620963 | We conclude that RPE disruption induced by high glucose plus IL-1β is prevented by Epo through the downstream signaling of JAK2 and PI3K/AKT pathways. |
| 6133 | 21620963 | Erythropoietin protects retinal pigment epithelial cells against the increase of permeability induced by diabetic conditions: essential role of JAK2/ PI3K signaling. |
| 6134 | 21620963 | The experiments were repeated in the presence of an Epo neutralizing antibody and specific inhibitors of JAK2 and PI3K (AG490 and LY294002, respectively). |
| 6135 | 21620963 | Epo treatment was able to prevent but not to restore the increase of permeability induced by high glucose plus IL-1β. |
| 6136 | 21620963 | In addition, Epo was able to increase cytosolic Ca(2+) with dependence on extracellular calcium influx and this effect was blocked by either JAK2 or PI3K inhibition. |
| 6137 | 21620963 | We conclude that RPE disruption induced by high glucose plus IL-1β is prevented by Epo through the downstream signaling of JAK2 and PI3K/AKT pathways. |
| 6138 | 21620963 | Erythropoietin protects retinal pigment epithelial cells against the increase of permeability induced by diabetic conditions: essential role of JAK2/ PI3K signaling. |
| 6139 | 21620963 | The experiments were repeated in the presence of an Epo neutralizing antibody and specific inhibitors of JAK2 and PI3K (AG490 and LY294002, respectively). |
| 6140 | 21620963 | Epo treatment was able to prevent but not to restore the increase of permeability induced by high glucose plus IL-1β. |
| 6141 | 21620963 | In addition, Epo was able to increase cytosolic Ca(2+) with dependence on extracellular calcium influx and this effect was blocked by either JAK2 or PI3K inhibition. |
| 6142 | 21620963 | We conclude that RPE disruption induced by high glucose plus IL-1β is prevented by Epo through the downstream signaling of JAK2 and PI3K/AKT pathways. |
| 6143 | 21620963 | Erythropoietin protects retinal pigment epithelial cells against the increase of permeability induced by diabetic conditions: essential role of JAK2/ PI3K signaling. |
| 6144 | 21620963 | The experiments were repeated in the presence of an Epo neutralizing antibody and specific inhibitors of JAK2 and PI3K (AG490 and LY294002, respectively). |
| 6145 | 21620963 | Epo treatment was able to prevent but not to restore the increase of permeability induced by high glucose plus IL-1β. |
| 6146 | 21620963 | In addition, Epo was able to increase cytosolic Ca(2+) with dependence on extracellular calcium influx and this effect was blocked by either JAK2 or PI3K inhibition. |
| 6147 | 21620963 | We conclude that RPE disruption induced by high glucose plus IL-1β is prevented by Epo through the downstream signaling of JAK2 and PI3K/AKT pathways. |
| 6148 | 21625639 | Sphingosine kinase 1 regulates the Akt/FOXO3a/Bim pathway and contributes to apoptosis resistance in glioma cells. |
| 6149 | 21625639 | Further mechanistic study examined the expression of Bcl-2 family members, including Bcl-2, Mcl-1, Bax and Bim, in SPHK1-overexpressing glioma cells and revealed that only pro-apoptotic Bim was downregulated by SPHK1. |
| 6150 | 21625639 | Moreover, the transcriptional level of Bim was also altered by SPHK1 in glioma cells. |
| 6151 | 21625639 | We next confirmed the correlation between SPHK1 and Bim expression in primary glioma specimens. |
| 6152 | 21625639 | Importantly, increasing SPHK1 expression in glioma cells markedly elevated Akt activity and phosphorylated inactivation of FOXO3a, which led to downregulation of Bim. |
| 6153 | 21625639 | A pharmacological approach showed that these effects of SPHK1 were dependent on phosphatidylinositol 3-kinase (PI3K). |
| 6154 | 21625639 | Furthermore, effects of SPHK1 on Akt/FOXO3a/Bim pathway could be reversed by SPHK1 specific RNA interference or SPHK1 inhibitor. |
| 6155 | 21625639 | Collectively, our results indicate that regulation of the Akt/FOXO3a/Bim pathway may be a novel mechanism by which SPHK1 protects glioma cells from apoptosis, thereby involved in glioma tumorigenesis. |
| 6156 | 21626780 | The levels of PI3K and GLUT4 in cardiac muscle were examined by immunoblotting and immunohistochemistry. |
| 6157 | 21626780 | The result showed that insulin in combination with selenium could significantly lower blood glucose and blood lipid levels and markedly restored the PI3K and GLUT4 levels in cardiac muscle. |
| 6158 | 21626780 | It could be concluded that there was cooperation between insulin and selenium, and that treatment of diabetic rats with combined doses of insulin and selenium increased cardiac glucose uptake by upregulating the level of PI3K-mediated GLUT4 in cardiac muscle, eventually ameliorating myocardial dysfunction. |
| 6159 | 21626780 | The levels of PI3K and GLUT4 in cardiac muscle were examined by immunoblotting and immunohistochemistry. |
| 6160 | 21626780 | The result showed that insulin in combination with selenium could significantly lower blood glucose and blood lipid levels and markedly restored the PI3K and GLUT4 levels in cardiac muscle. |
| 6161 | 21626780 | It could be concluded that there was cooperation between insulin and selenium, and that treatment of diabetic rats with combined doses of insulin and selenium increased cardiac glucose uptake by upregulating the level of PI3K-mediated GLUT4 in cardiac muscle, eventually ameliorating myocardial dysfunction. |
| 6162 | 21626780 | The levels of PI3K and GLUT4 in cardiac muscle were examined by immunoblotting and immunohistochemistry. |
| 6163 | 21626780 | The result showed that insulin in combination with selenium could significantly lower blood glucose and blood lipid levels and markedly restored the PI3K and GLUT4 levels in cardiac muscle. |
| 6164 | 21626780 | It could be concluded that there was cooperation between insulin and selenium, and that treatment of diabetic rats with combined doses of insulin and selenium increased cardiac glucose uptake by upregulating the level of PI3K-mediated GLUT4 in cardiac muscle, eventually ameliorating myocardial dysfunction. |
| 6165 | 21647634 | Monoclonal antibody to six transmembrane epithelial antigen of prostate-4 influences insulin sensitivity by attenuating phosphorylation of P13K (P85) and Akt: possible mitochondrial mechanism. |
| 6166 | 21647634 | We examined the effects of anti-six-transmembrane epithelial antigen of the prostate-4 (STEAP4) antibodies on glucose transport in mature adipocytes and determined the mechanism of insulin resistance in obesity. |
| 6167 | 21647634 | Western blotting was performed to determine STEAP4 expression, to assess translocation of insulin-sensitive glucose transporter 4 (GLUT4), and to measure phosphorylation and total protein content of insulin-signaling proteins. |
| 6168 | 21647634 | After the application of anti-STEAP4 antibodies at 0.002 mg/mL, adipocytes exhibited reduced insulin-stimulated glucose transport by attenuating the phosphorylation of IRS-1, PI3K (p85), and Akt. |
| 6169 | 21647634 | In conclusion, (i) STEAP4 regulates the function of IRS-1, PI3K, and Akt and decreases insulin-induced GLUT4 translocation and glucose uptake; (ii) ROS-related mitochondrial dysfunction may be related to a reduced IRS-1 correlation with the PI3K signaling pathway, leading to insulin resistance. |
| 6170 | 21647634 | These observations highlight the potential role of STEAP4 in glucose homeostasis and possibly in the pathophysiology of type 2 diabetes related to obesity and may provide new insights into the mechanisms of insulin resistance in obesity. |
| 6171 | 21647634 | Monoclonal antibody to six transmembrane epithelial antigen of prostate-4 influences insulin sensitivity by attenuating phosphorylation of P13K (P85) and Akt: possible mitochondrial mechanism. |
| 6172 | 21647634 | We examined the effects of anti-six-transmembrane epithelial antigen of the prostate-4 (STEAP4) antibodies on glucose transport in mature adipocytes and determined the mechanism of insulin resistance in obesity. |
| 6173 | 21647634 | Western blotting was performed to determine STEAP4 expression, to assess translocation of insulin-sensitive glucose transporter 4 (GLUT4), and to measure phosphorylation and total protein content of insulin-signaling proteins. |
| 6174 | 21647634 | After the application of anti-STEAP4 antibodies at 0.002 mg/mL, adipocytes exhibited reduced insulin-stimulated glucose transport by attenuating the phosphorylation of IRS-1, PI3K (p85), and Akt. |
| 6175 | 21647634 | In conclusion, (i) STEAP4 regulates the function of IRS-1, PI3K, and Akt and decreases insulin-induced GLUT4 translocation and glucose uptake; (ii) ROS-related mitochondrial dysfunction may be related to a reduced IRS-1 correlation with the PI3K signaling pathway, leading to insulin resistance. |
| 6176 | 21647634 | These observations highlight the potential role of STEAP4 in glucose homeostasis and possibly in the pathophysiology of type 2 diabetes related to obesity and may provide new insights into the mechanisms of insulin resistance in obesity. |
| 6177 | 21673097 | Mechanisms of estradiol-induced insulin secretion by the G protein-coupled estrogen receptor GPR30/GPER in pancreatic beta-cells. |
| 6178 | 21673097 | Because little is known regarding the signaling mechanisms involved in estradiol-mediated insulin secretion, we investigated the role of the G protein-coupled receptor 30, now designated G protein-coupled estrogen receptor (GPER), in activating signal transduction cascades in β-cells, leading to secretion of insulin. |
| 6179 | 21673097 | GPER function in estradiol-induced signaling in the pancreatic β-cell line MIN6 was assessed using small interfering RNA and GPER-selective ligands (G-1 and G15) and in islets isolated from wild-type and GPER knockout mice. |
| 6180 | 21673097 | GPER is expressed in MIN6 cells, where estradiol and the GPER-selective agonist G-1 mediate calcium mobilization and activation of ERK and phosphatidylinositol 3-kinase. |
| 6181 | 21673097 | Both estradiol and G-1 induced insulin secretion under low- and high-glucose conditions, which was inhibited by pretreatment with GPER antagonist G15 as well as depletion of GPER by small interfering RNA. |
| 6182 | 21673097 | Insulin secretion in response to estradiol and G-1 was dependent on epidermal growth factor receptor and ERK activation and further modulated by phosphatidylinositol 3-kinase activity. |
| 6183 | 21673097 | In islets isolated from wild-type mice, the GPER antagonist G15 inhibited insulin secretion induced by estradiol and G-1, both of which failed to induce insulin secretion in islets obtained from GPER knockout mice. |
| 6184 | 21673097 | Our results indicate that GPER activation of the epidermal growth factor receptor and ERK in response to estradiol treatment plays a critical role in the secretion of insulin from β-cells. |
| 6185 | 21673097 | Mechanisms of estradiol-induced insulin secretion by the G protein-coupled estrogen receptor GPR30/GPER in pancreatic beta-cells. |
| 6186 | 21673097 | Because little is known regarding the signaling mechanisms involved in estradiol-mediated insulin secretion, we investigated the role of the G protein-coupled receptor 30, now designated G protein-coupled estrogen receptor (GPER), in activating signal transduction cascades in β-cells, leading to secretion of insulin. |
| 6187 | 21673097 | GPER function in estradiol-induced signaling in the pancreatic β-cell line MIN6 was assessed using small interfering RNA and GPER-selective ligands (G-1 and G15) and in islets isolated from wild-type and GPER knockout mice. |
| 6188 | 21673097 | GPER is expressed in MIN6 cells, where estradiol and the GPER-selective agonist G-1 mediate calcium mobilization and activation of ERK and phosphatidylinositol 3-kinase. |
| 6189 | 21673097 | Both estradiol and G-1 induced insulin secretion under low- and high-glucose conditions, which was inhibited by pretreatment with GPER antagonist G15 as well as depletion of GPER by small interfering RNA. |
| 6190 | 21673097 | Insulin secretion in response to estradiol and G-1 was dependent on epidermal growth factor receptor and ERK activation and further modulated by phosphatidylinositol 3-kinase activity. |
| 6191 | 21673097 | In islets isolated from wild-type mice, the GPER antagonist G15 inhibited insulin secretion induced by estradiol and G-1, both of which failed to induce insulin secretion in islets obtained from GPER knockout mice. |
| 6192 | 21673097 | Our results indicate that GPER activation of the epidermal growth factor receptor and ERK in response to estradiol treatment plays a critical role in the secretion of insulin from β-cells. |
| 6193 | 21684255 | We have recently shown that in macrophages proper operation of the survival pathways phosphatidylinositol-3-kinase (PI3K)/AKT and nuclear factor kappa B (NFkB) has an obligatory requirement for constitutive, non-regulated Ca(2+) influx. |
| 6194 | 21684255 | Treatment of TRPC3(+/+) macrophages with the pro-apoptotic cytokine TNFα induced time-dependent phosphorylation of IκBα, AKT and BAD, and this was drastically reduced in TRPC3(-/-) macrophages. |
| 6195 | 21693679 | Apolipoprotein CIII reduces proinflammatory cytokine-induced apoptosis in rat pancreatic islets via the Akt prosurvival pathway. |
| 6196 | 21693679 | Apolipoprotein CIII (ApoCIII) is mainly synthesized in the liver and is important for triglyceride metabolism. |
| 6197 | 21693679 | In the presence of the islet-cytotoxic cytokines IL-1β + interferon-γ, ApoCIII reduced cytokine-mediated islet cell death and impairment of β-cell function. |
| 6198 | 21693679 | ApoCIII had no effects on mitogen-activated protein kinases (c-Jun N-terminal kinase, p38, and ERK) and had no impact on IL-1β-induced c-Jun N-terminal kinase activation. |
| 6199 | 21693679 | Further, ApoCIII caused degradation of the nuclear factor κB-inhibitor inhibitor of κB and stimulated Ser473-phosphorylation of the survival serine-threonine kinase Akt. |
| 6200 | 21693679 | Inhibition of the Akt signaling pathway by the phosphatidylinositol 3 kinase inhibitor LY294002 counteracted the antiapoptotic effect of ApoCIII on cytokine-induced apoptosis. |
| 6201 | 21693679 | We conclude that ApoCIII in the presence of T1D-relevant proinflammatory cytokines reduces rat pancreatic islet cell apoptosis via Akt. |
| 6202 | 21753738 | Here, we demonstrate that a reduction in phosphoinositide 3-kinase (PI3K) signaling is a major contributor to the altered function of CaV1.2 in db/db cardiac myocytes. |
| 6203 | 21753738 | Akt1 and Akt2 were as effective as PIP3 in restoring the ICa,L density in db/db myocytes but did not affect the voltage dependence of current activation. |
| 6204 | 21753738 | These results indicate that a defect in PI3K/PIP3/Akt/PKC-λ signaling is mainly responsible for the depressed CaV1.2 function in the hearts of db/db mice with type 2 diabetes. |
| 6205 | 21753738 | Here, we demonstrate that a reduction in phosphoinositide 3-kinase (PI3K) signaling is a major contributor to the altered function of CaV1.2 in db/db cardiac myocytes. |
| 6206 | 21753738 | Akt1 and Akt2 were as effective as PIP3 in restoring the ICa,L density in db/db myocytes but did not affect the voltage dependence of current activation. |
| 6207 | 21753738 | These results indicate that a defect in PI3K/PIP3/Akt/PKC-λ signaling is mainly responsible for the depressed CaV1.2 function in the hearts of db/db mice with type 2 diabetes. |
| 6208 | 21765243 | Human placental lactogen (hPL-A) activates signaling pathways linked to cell survival and improves insulin secretion in human pancreatic islets. |
| 6209 | 21765243 | Among factors with mitogenic activity on pancreatic β-cells, human placental lactogen (hPL) showed stronger activity when compared to the other lactogen hormones: growth hormone (GH) and prolactin (PRL). |
| 6210 | 21765243 | Indeed, the antiapoptotic role of hPL-A was mediated by PI3K, p38 and it was independent by PKA, Erk1/2. |
| 6211 | 21765243 | Moreover, hPL-A induced PDX-1 intracellular expression, improving beta cell activity and ameliorating insulin secretion in response to high glucose stimulation. |
| 6212 | 21776823 | Molecular and cellular studies indicated that metformin significantly elevated p53 and Bax levels and reduced STAT3 and Bcl-2. |
| 6213 | 21776823 | Receptor inhibitor studies indicated that p53 activation was mediated through insulin receptor (IR), not insulin-like growth factor-1 receptor (IGF-IR). |
| 6214 | 21776823 | Furthermore, MEK inhibitor significantly suppressed metformin-induced p53 and Bax elevation while ERK inhibitor generated a slight reduction in p53 levels. |
| 6215 | 21776823 | In contrast, PI3K inhibitor did not produce any effect on the metformin-elevated p53 levels. |
| 6216 | 21776823 | Finally, SAPK/JNK, known to be involved in apoptosis, was activated in cells treated with metformin and the activation appeared to occur downstream of ERK. |
| 6217 | 21776823 | All these results suggested that metformin activated p53, Bax, and induced tumor cell apoptosis through the ERK signaling pathway. |
| 6218 | 21776823 | This pathway has not been previously described for IR, p53, Bax activation, or apoptosis. |
| 6219 | 21803028 | Des-aspartate-angiotensin-I and angiotensin IV improve glucose tolerance and insulin signalling in diet-induced hyperglycaemic mice. |
| 6220 | 21803028 | Insulin-induced activation of IR, IRS-1, IRS-1-PI3K coupling, phosphorylation of Akt, and GLUT4 translocation were attenuated in skeletal muscles of HFD animals. |
| 6221 | 21803028 | In corresponding Ang-IV treated animals, insulin induced IRAP and PI3K interaction, activation of pAkt and GLUT4 translocation, but no corresponding activation of IR, IRS-1 and IRS-1-PI3K coupling were observed. |
| 6222 | 21803028 | DAA-I acts via the angiotensin AT(1) receptor and activates the insulin pathway. |
| 6223 | 21803028 | Ang-IV acts via IRAP, which couples PI3K and activates the later part of the insulin pathway. |
| 6224 | 21803028 | Des-aspartate-angiotensin-I and angiotensin IV improve glucose tolerance and insulin signalling in diet-induced hyperglycaemic mice. |
| 6225 | 21803028 | Insulin-induced activation of IR, IRS-1, IRS-1-PI3K coupling, phosphorylation of Akt, and GLUT4 translocation were attenuated in skeletal muscles of HFD animals. |
| 6226 | 21803028 | In corresponding Ang-IV treated animals, insulin induced IRAP and PI3K interaction, activation of pAkt and GLUT4 translocation, but no corresponding activation of IR, IRS-1 and IRS-1-PI3K coupling were observed. |
| 6227 | 21803028 | DAA-I acts via the angiotensin AT(1) receptor and activates the insulin pathway. |
| 6228 | 21803028 | Ang-IV acts via IRAP, which couples PI3K and activates the later part of the insulin pathway. |
| 6229 | 21809954 | Prunus yedoensis Matsum. stimulates glucose uptake in L6 rat skeletal muscle cells by activating AMP-activated protein kinase and phosphatidylinositol 3-kinase/Akt pathways. |
| 6230 | 21809954 | Prunus yedoensis leaf extract (PLE) increased the glucose uptake of phosphorylatinginsulin receptor substrate (IRS)-1, 3'-phosphoinositide-dependent kinase (PDK)-1 and Akt PLE, and also increased the phosphorylation of AMP-activated protein kinase (AMPK) and p38 mitogen-activated protein kinase (p38 MAPK). |
| 6231 | 21809954 | PLE-stimulated glucose uptake was blocked by an AMPK inhibitor (Compound C) and a p38 MAPK inhibitor (SB203580). |
| 6232 | 21809954 | Inhibition of AMPK activity reduced p38 MAPK phosphorylation, whereas the inhibition of p38 MAPK activity did not affect AMPK phosphorylation. |
| 6233 | 21809954 | Our results demonstrate that PLE stimulated glucose uptake by activating both insulin signalling and AMPK-p38 MAPK pathways. |
| 6234 | 21810948 | Acute insulin treatment resulted in time- and concentration-dependent activation of the signaling cascade, including phosphorylation of the insulin receptor, Akt, p70S6K, and glycogen synthase kinase-3β. |
| 6235 | 21810948 | Chronic insulin treatment resulted in increased basal Akt phosphorylation. |
| 6236 | 21810948 | More importantly, acute insulin stimulation after chronic insulin treatment resulted in blunted phosphorylation of Akt, p70S6K, and glycogen synthase kinase-3β. |
| 6237 | 21810948 | Interestingly, when the cells were treated with phosphatidylinositol 3-kinase pathway inhibitor, but not MAPK pathway inhibitor, chronic insulin treatment did not block acute insulin treatment-induced Akt phosphorylation. |
| 6238 | 21810948 | Insulin-induced Akt phosphorylation was lower in dorsal root ganglion neurons from BKS-db/db compared with control BKS-db+ mice. |
| 6239 | 21822424 | Both IPC- and Ipost-mediated myocardial protection is predominantly mediated by stimulating PI3K/Akt and associated GSK-3β pathway while diabetes-mediated pathogenic effects are found to be mediated by inhibiting PI3K/Akt and associated GSK-3β pathway. |
| 6240 | 21822424 | Increasing evidence implies that diabetic inhibition of IPC- and Ipost-mediated myocardial protection may be mediated by inhibiting PI3K/Akt and associated GSK-3β pathway. |
| 6241 | 21822424 | Therefore any strategy to activate PI3K/Akt and associated GSK-3β pathway to release the diabetic inhibition of both IPC and Ipost-mediated myocardial protection may provide the protective effect against ischemia/reperfusion injuries. |
| 6242 | 21822424 | Both IPC- and Ipost-mediated myocardial protection is predominantly mediated by stimulating PI3K/Akt and associated GSK-3β pathway while diabetes-mediated pathogenic effects are found to be mediated by inhibiting PI3K/Akt and associated GSK-3β pathway. |
| 6243 | 21822424 | Increasing evidence implies that diabetic inhibition of IPC- and Ipost-mediated myocardial protection may be mediated by inhibiting PI3K/Akt and associated GSK-3β pathway. |
| 6244 | 21822424 | Therefore any strategy to activate PI3K/Akt and associated GSK-3β pathway to release the diabetic inhibition of both IPC and Ipost-mediated myocardial protection may provide the protective effect against ischemia/reperfusion injuries. |
| 6245 | 21822424 | Both IPC- and Ipost-mediated myocardial protection is predominantly mediated by stimulating PI3K/Akt and associated GSK-3β pathway while diabetes-mediated pathogenic effects are found to be mediated by inhibiting PI3K/Akt and associated GSK-3β pathway. |
| 6246 | 21822424 | Increasing evidence implies that diabetic inhibition of IPC- and Ipost-mediated myocardial protection may be mediated by inhibiting PI3K/Akt and associated GSK-3β pathway. |
| 6247 | 21822424 | Therefore any strategy to activate PI3K/Akt and associated GSK-3β pathway to release the diabetic inhibition of both IPC and Ipost-mediated myocardial protection may provide the protective effect against ischemia/reperfusion injuries. |
| 6248 | 21829168 | Egr-1 decreases adipocyte insulin sensitivity by tilting PI3K/Akt and MAPK signal balance in mice. |
| 6249 | 21829168 | It is well known that insulin can activate both PI3K/Akt pathway, which is responsible for glucose uptake, and MAPK pathway, which is crucial for insulin resistance formation. |
| 6250 | 21829168 | Here, we show that an early response transcription factor Egr-1 could tilt the signalling balance by blocking PI3K/Akt signalling through PTEN and augmenting Erk/MAPK signalling through GGPPS, resulting in insulin resistance in adipocytes. |
| 6251 | 21829168 | Egr-1, PTEN and GGPPS are upregulated in the fat tissue of T2DM patients and db/db mice. |
| 6252 | 21829168 | Egr-1 overexpression in epididymal fat induced systematic insulin resistance in wild-type mice, and loss of Egr-1 function improved whole-body insulin sensitivity in diabetic mice, which is mediated by Egr-1 controlled PI3K/Akt and Erk/MAPK signalling balance. |
| 6253 | 21829168 | Therefore, we have revealed, for the first time, the mechanism by which Egr-1 induces insulin resistance under hyperinsulinism stress, which provides an ideal pharmacological target since inhibiting Egr-1 can simultaneously block MAPK and augment PI3K/Akt activation during insulin stimulation. |
| 6254 | 21829168 | Egr-1 decreases adipocyte insulin sensitivity by tilting PI3K/Akt and MAPK signal balance in mice. |
| 6255 | 21829168 | It is well known that insulin can activate both PI3K/Akt pathway, which is responsible for glucose uptake, and MAPK pathway, which is crucial for insulin resistance formation. |
| 6256 | 21829168 | Here, we show that an early response transcription factor Egr-1 could tilt the signalling balance by blocking PI3K/Akt signalling through PTEN and augmenting Erk/MAPK signalling through GGPPS, resulting in insulin resistance in adipocytes. |
| 6257 | 21829168 | Egr-1, PTEN and GGPPS are upregulated in the fat tissue of T2DM patients and db/db mice. |
| 6258 | 21829168 | Egr-1 overexpression in epididymal fat induced systematic insulin resistance in wild-type mice, and loss of Egr-1 function improved whole-body insulin sensitivity in diabetic mice, which is mediated by Egr-1 controlled PI3K/Akt and Erk/MAPK signalling balance. |
| 6259 | 21829168 | Therefore, we have revealed, for the first time, the mechanism by which Egr-1 induces insulin resistance under hyperinsulinism stress, which provides an ideal pharmacological target since inhibiting Egr-1 can simultaneously block MAPK and augment PI3K/Akt activation during insulin stimulation. |
| 6260 | 21829168 | Egr-1 decreases adipocyte insulin sensitivity by tilting PI3K/Akt and MAPK signal balance in mice. |
| 6261 | 21829168 | It is well known that insulin can activate both PI3K/Akt pathway, which is responsible for glucose uptake, and MAPK pathway, which is crucial for insulin resistance formation. |
| 6262 | 21829168 | Here, we show that an early response transcription factor Egr-1 could tilt the signalling balance by blocking PI3K/Akt signalling through PTEN and augmenting Erk/MAPK signalling through GGPPS, resulting in insulin resistance in adipocytes. |
| 6263 | 21829168 | Egr-1, PTEN and GGPPS are upregulated in the fat tissue of T2DM patients and db/db mice. |
| 6264 | 21829168 | Egr-1 overexpression in epididymal fat induced systematic insulin resistance in wild-type mice, and loss of Egr-1 function improved whole-body insulin sensitivity in diabetic mice, which is mediated by Egr-1 controlled PI3K/Akt and Erk/MAPK signalling balance. |
| 6265 | 21829168 | Therefore, we have revealed, for the first time, the mechanism by which Egr-1 induces insulin resistance under hyperinsulinism stress, which provides an ideal pharmacological target since inhibiting Egr-1 can simultaneously block MAPK and augment PI3K/Akt activation during insulin stimulation. |
| 6266 | 21829168 | Egr-1 decreases adipocyte insulin sensitivity by tilting PI3K/Akt and MAPK signal balance in mice. |
| 6267 | 21829168 | It is well known that insulin can activate both PI3K/Akt pathway, which is responsible for glucose uptake, and MAPK pathway, which is crucial for insulin resistance formation. |
| 6268 | 21829168 | Here, we show that an early response transcription factor Egr-1 could tilt the signalling balance by blocking PI3K/Akt signalling through PTEN and augmenting Erk/MAPK signalling through GGPPS, resulting in insulin resistance in adipocytes. |
| 6269 | 21829168 | Egr-1, PTEN and GGPPS are upregulated in the fat tissue of T2DM patients and db/db mice. |
| 6270 | 21829168 | Egr-1 overexpression in epididymal fat induced systematic insulin resistance in wild-type mice, and loss of Egr-1 function improved whole-body insulin sensitivity in diabetic mice, which is mediated by Egr-1 controlled PI3K/Akt and Erk/MAPK signalling balance. |
| 6271 | 21829168 | Therefore, we have revealed, for the first time, the mechanism by which Egr-1 induces insulin resistance under hyperinsulinism stress, which provides an ideal pharmacological target since inhibiting Egr-1 can simultaneously block MAPK and augment PI3K/Akt activation during insulin stimulation. |
| 6272 | 21829168 | Egr-1 decreases adipocyte insulin sensitivity by tilting PI3K/Akt and MAPK signal balance in mice. |
| 6273 | 21829168 | It is well known that insulin can activate both PI3K/Akt pathway, which is responsible for glucose uptake, and MAPK pathway, which is crucial for insulin resistance formation. |
| 6274 | 21829168 | Here, we show that an early response transcription factor Egr-1 could tilt the signalling balance by blocking PI3K/Akt signalling through PTEN and augmenting Erk/MAPK signalling through GGPPS, resulting in insulin resistance in adipocytes. |
| 6275 | 21829168 | Egr-1, PTEN and GGPPS are upregulated in the fat tissue of T2DM patients and db/db mice. |
| 6276 | 21829168 | Egr-1 overexpression in epididymal fat induced systematic insulin resistance in wild-type mice, and loss of Egr-1 function improved whole-body insulin sensitivity in diabetic mice, which is mediated by Egr-1 controlled PI3K/Akt and Erk/MAPK signalling balance. |
| 6277 | 21829168 | Therefore, we have revealed, for the first time, the mechanism by which Egr-1 induces insulin resistance under hyperinsulinism stress, which provides an ideal pharmacological target since inhibiting Egr-1 can simultaneously block MAPK and augment PI3K/Akt activation during insulin stimulation. |
| 6278 | 21861051 | Transforming growth factor-β1 (TGF-β1)-activated phosphoinositide-3-kinase (PI3K)-protein kinase B (PKB/Akt) pathway is intimately related to the development of diabetic nephropathy (DN), which is negatively regulated by phosphatase and tensin homolog deleted on chromosome ten (PTEN). |
| 6279 | 21861051 | In addition, immunohistochemistry staining and Western blotting were employed to detect the protein expression of PTEN, TGF-β1, PI3Kp110α, Akt1, p-Akt1 (Ser(473)), fibronectin (FN) and Collagen IV, respectively. |
| 6280 | 21861051 | The expression of PTEN in the diabetic group was significantly reduced than that in the control group (P < 0.05), and the expression of p-Akt1 (Ser(473)) increased remarkably in the diabetic group which had the similar trend to Akt1 (P < 0.05). |
| 6281 | 21861051 | The data suggest that the down-regulation of PTEN in renal tissue of DM rats may promote the PI3K-PKB/Akt pathway over-activated by TGF-β1, which facilitates the initiation and development of DN. |
| 6282 | 21913799 | TGF-β stimulates biglycan core protein synthesis but not glycosaminoglycan chain elongation via Akt phosphorylation in vascular smooth muscle. |
| 6283 | 21913799 | We investigated whether TGF-β-mediated proteoglycan synthesis is via PI3K/Akt. |
| 6284 | 21913799 | Akt phosphorylation was blocked by Akt1/2 inhibitor SN30978; however, it did not block Smad2 phosphorylation at either the carboxy or linker regions indicating that TGF-β-mediated Akt phosphorylation is independent of Smad2 signalling. |
| 6285 | 21913799 | Treatment with SN30978 showed a concentration-dependent decrease in TGF-β-mediated [(35)S]-sulphate and [(35)S]-Met/Cys incorporation into secreted proteoglycans; however, SDS-PAGE showed no change in biglycan size. |
| 6286 | 21913799 | Our findings demonstrate that Akt is a downstream signalling component of TGF-β-mediated biglycan core protein synthesis but not glycosaminoglycan chain hyper-elongation in VSM. |
| 6287 | 21953448 | Hydrogen sulfide and L-cysteine increase phosphatidylinositol 3,4,5-trisphosphate (PIP3) and glucose utilization by inhibiting phosphatase and tensin homolog (PTEN) protein and activating phosphoinositide 3-kinase (PI3K)/serine/threonine protein kinase (AKT)/protein kinase Cζ/λ (PKCζ/λ) in 3T3l1 adipocytes. |
| 6288 | 21953448 | H(2)S and LC caused phosphatidylinositol 3-kinase activation and PTEN inhibition. |
| 6289 | 21953448 | Treatment with LC, H(2)S, or PIP3 increased the phosphorylation of IRS1, AKT, and PKCζ/λ as well as GLUT4 activation and glucose utilization in HG-treated cells. |
| 6290 | 21953448 | The PIP3 increase is mediated by PI3K activation and inhibition of PTEN but not of SHIP2. |
| 6291 | 21953448 | Hydrogen sulfide and L-cysteine increase phosphatidylinositol 3,4,5-trisphosphate (PIP3) and glucose utilization by inhibiting phosphatase and tensin homolog (PTEN) protein and activating phosphoinositide 3-kinase (PI3K)/serine/threonine protein kinase (AKT)/protein kinase Cζ/λ (PKCζ/λ) in 3T3l1 adipocytes. |
| 6292 | 21953448 | H(2)S and LC caused phosphatidylinositol 3-kinase activation and PTEN inhibition. |
| 6293 | 21953448 | Treatment with LC, H(2)S, or PIP3 increased the phosphorylation of IRS1, AKT, and PKCζ/λ as well as GLUT4 activation and glucose utilization in HG-treated cells. |
| 6294 | 21953448 | The PIP3 increase is mediated by PI3K activation and inhibition of PTEN but not of SHIP2. |
| 6295 | 21953448 | Hydrogen sulfide and L-cysteine increase phosphatidylinositol 3,4,5-trisphosphate (PIP3) and glucose utilization by inhibiting phosphatase and tensin homolog (PTEN) protein and activating phosphoinositide 3-kinase (PI3K)/serine/threonine protein kinase (AKT)/protein kinase Cζ/λ (PKCζ/λ) in 3T3l1 adipocytes. |
| 6296 | 21953448 | H(2)S and LC caused phosphatidylinositol 3-kinase activation and PTEN inhibition. |
| 6297 | 21953448 | Treatment with LC, H(2)S, or PIP3 increased the phosphorylation of IRS1, AKT, and PKCζ/λ as well as GLUT4 activation and glucose utilization in HG-treated cells. |
| 6298 | 21953448 | The PIP3 increase is mediated by PI3K activation and inhibition of PTEN but not of SHIP2. |
| 6299 | 21957263 | Brief insulin preapplication restored TRPV1-dependent modulation of glutamate release in a PKC- and PI3K-dependent manner. |
| 6300 | 21957263 | The restorative effect of insulin was prevented by brefeldin A, suggesting that insulin induced TRPV1 receptor trafficking to the terminal membrane. |
| 6301 | 21957263 | Central vagal circuits critical to the autonomic regulation of metabolism undergo insulin-dependent synaptic plasticity involving TRPV1 receptor modulation in diabetic mice after several days of chronic hyperglycemia. |
| 6302 | 21964769 | The Akt/FoxO1/p27 pathway mediates the proliferative action of liraglutide in β cells. |
| 6303 | 21964769 | In the present study, we investigated the role of Akt/FoxO1/p27 signaling in liraglutide-induced β-cell proliferation. |
| 6304 | 21964769 | The expression of Akt/FoxO1/p27 was detected by quantitative real-time PCR and Western blotting. |
| 6305 | 21964769 | Western blot analysis revealed that the phosphorylation of Akt and FoxO1 was markedly elevated following exposure to liraglutide. |
| 6306 | 21964769 | Therefore, we conclude that liraglutide increased the β-cell mass by upregulating β-cell proliferation and that the proliferative action of liraglutide in β cells was mediated by activation of PI-3K/Akt, which resulted in inactivation of FoxO1 and decreased p27. |
| 6307 | 21969604 | Insulin exerts many of its metabolic actions via the canonical phosphatidylinositide 3 kinase (PI3K)/Akt pathway, leading to phosphorylation and 14-3-3 binding of key metabolic targets. |
| 6308 | 21969604 | We previously identified a GTPase-activating protein (GAP) for Rac1 called RhoGAP22 as an insulin-responsive 14-3-3 binding protein. |
| 6309 | 21969604 | Insulin increased 14-3-3 binding to RhoGAP22 fourfold, and this effect was PI3K dependent. |
| 6310 | 21969604 | Mutation of the catalytic arginine of the GAP domain of RhoGAP22 potentiated growth factor-stimulated Rac1 GTP loading. |
| 6311 | 21969604 | We propose that insulin and possibly growth factors such as platelet-derived growth factor may play a novel role in regulating cell migration and motility via the Akt-dependent phosphorylation of RhoGAP22, leading to modulation of Rac1 activity. |
| 6312 | 21969604 | Insulin exerts many of its metabolic actions via the canonical phosphatidylinositide 3 kinase (PI3K)/Akt pathway, leading to phosphorylation and 14-3-3 binding of key metabolic targets. |
| 6313 | 21969604 | We previously identified a GTPase-activating protein (GAP) for Rac1 called RhoGAP22 as an insulin-responsive 14-3-3 binding protein. |
| 6314 | 21969604 | Insulin increased 14-3-3 binding to RhoGAP22 fourfold, and this effect was PI3K dependent. |
| 6315 | 21969604 | Mutation of the catalytic arginine of the GAP domain of RhoGAP22 potentiated growth factor-stimulated Rac1 GTP loading. |
| 6316 | 21969604 | We propose that insulin and possibly growth factors such as platelet-derived growth factor may play a novel role in regulating cell migration and motility via the Akt-dependent phosphorylation of RhoGAP22, leading to modulation of Rac1 activity. |
| 6317 | 22005953 | Essential fatty acids form precursors to both pro- and anti-inflammatory molecules have been shown to regulate gene expression, enzyme activity, modulate inflammation and immune response, gluconeogenesis via direct and indirect pathways, function directly as agonists of a number of G protein-coupled receptors, activate phosphatidylinositol 3-kinase/Akt and p44/42 mitogen-activated protein kinases, and stimulate cell proliferation via Ca(2+), phospholipase C/protein kinase, events that are also necessary for stem cell survival, proliferation, and differentiation. |
| 6318 | 22012952 | Insulin decreases myocardial adiponectin receptor 1 expression via PI3K/Akt and FoxO1 pathway. |
| 6319 | 22015290 | Recent research has focused on insulin as a potential biologic mediator of these effects given frequent expression of insulin/IGF-1 receptors on breast cancer cells which, when activated, can stimulate signaling through PI3K and Ras-Raf signaling pathways to enhance proliferation. |
| 6320 | 22019900 | Phosphoinositides signalling in cancer: focus on PI3K and PLC. |
| 6321 | 22026163 | Ibrolipim attenuates high glucose-induced endothelial dysfunction in cultured human umbilical vein endothelial cells via PI3K/Akt pathway. |
| 6322 | 22031849 | Site 1 protease was required, since its inhibition by AEBSF prevented SREBP-1 activation. |
| 6323 | 22031849 | SCAP, the ER-associated chaperone for SREBP-1, was also necessary since its inhibitor fatostatin also blocked SREBP-1 activation. |
| 6324 | 22031849 | Signaling through the EGFR/phosphatidylinositol 3-kinase (PI3K) pathway, which we previously showed mediates HG-induced TGF-β1 upregulation, and through RhoA, were upstream of SREBP-1 activation (Wu D, Peng F, Zhang B, Ingram AJ, Gao B, Krepinsky JC. |
| 6325 | 22031849 | Thus HG-induced SREBP-1 activation requires EGFR/PI3K/RhoA signaling and SCAP-mediated transport to the Golgi for its proteolytic cleavage. |
| 6326 | 22031849 | Site 1 protease was required, since its inhibition by AEBSF prevented SREBP-1 activation. |
| 6327 | 22031849 | SCAP, the ER-associated chaperone for SREBP-1, was also necessary since its inhibitor fatostatin also blocked SREBP-1 activation. |
| 6328 | 22031849 | Signaling through the EGFR/phosphatidylinositol 3-kinase (PI3K) pathway, which we previously showed mediates HG-induced TGF-β1 upregulation, and through RhoA, were upstream of SREBP-1 activation (Wu D, Peng F, Zhang B, Ingram AJ, Gao B, Krepinsky JC. |
| 6329 | 22031849 | Thus HG-induced SREBP-1 activation requires EGFR/PI3K/RhoA signaling and SCAP-mediated transport to the Golgi for its proteolytic cleavage. |
| 6330 | 22037215 | Inhibiting PI3K reduces mammary tumor growth and induces hyperglycemia in a mouse model of insulin resistance and hyperinsulinemia. |
| 6331 | 22037215 | In the MKR mouse model of insulin resistance, we have previously shown increased activation of the phosphatidylinositol 3-kinase (PI3K)/Akt/mTOR pathway in association with accelerated mammary tumor growth. |
| 6332 | 22037215 | NVP-BKM120 treatment decreased phosphorylation of Akt and S6 ribosomal protein (S6rp); no change in Erk1/2 phosphorylation was seen. |
| 6333 | 22037215 | Therefore, we examined whether the oral PI3K/mTOR inhibitor NVP-BEZ235 augmented the tumor suppressing effects of PI3K inhibition. |
| 6334 | 22037215 | We also investigated the effect of targeted PI3K/mTOR inhibition on PI3K/Akt/mTOR and Erk1/2 signaling, and the potential effects on glycemia. |
| 6335 | 22037215 | NVP-BEZ235 suppressed the growth of Met-1 and MCNeuA tumor orthografts, and decreased Akt and S6rp phosphorylation, despite increased Erk1/2 phosphorylation in Met-1 orthografts of MKR mice. |
| 6336 | 22037215 | Overall, the results of this study demonstrated that inhibiting PI3K/Akt/mTOR signaling with the oral agents NVP-BKM120 and NVP-BEZ235 decreased mammary tumor growth in the hyperinsulinemic MKR mouse. |
| 6337 | 22037215 | Inhibiting PI3K alone led to more severe metabolic derangement than inhibiting both PI3K and mTOR. |
| 6338 | 22037215 | Therefore, PI3K may be an important target for the treatment of breast cancer in women with insulin resistance. |
| 6339 | 22037215 | Inhibiting PI3K reduces mammary tumor growth and induces hyperglycemia in a mouse model of insulin resistance and hyperinsulinemia. |
| 6340 | 22037215 | In the MKR mouse model of insulin resistance, we have previously shown increased activation of the phosphatidylinositol 3-kinase (PI3K)/Akt/mTOR pathway in association with accelerated mammary tumor growth. |
| 6341 | 22037215 | NVP-BKM120 treatment decreased phosphorylation of Akt and S6 ribosomal protein (S6rp); no change in Erk1/2 phosphorylation was seen. |
| 6342 | 22037215 | Therefore, we examined whether the oral PI3K/mTOR inhibitor NVP-BEZ235 augmented the tumor suppressing effects of PI3K inhibition. |
| 6343 | 22037215 | We also investigated the effect of targeted PI3K/mTOR inhibition on PI3K/Akt/mTOR and Erk1/2 signaling, and the potential effects on glycemia. |
| 6344 | 22037215 | NVP-BEZ235 suppressed the growth of Met-1 and MCNeuA tumor orthografts, and decreased Akt and S6rp phosphorylation, despite increased Erk1/2 phosphorylation in Met-1 orthografts of MKR mice. |
| 6345 | 22037215 | Overall, the results of this study demonstrated that inhibiting PI3K/Akt/mTOR signaling with the oral agents NVP-BKM120 and NVP-BEZ235 decreased mammary tumor growth in the hyperinsulinemic MKR mouse. |
| 6346 | 22037215 | Inhibiting PI3K alone led to more severe metabolic derangement than inhibiting both PI3K and mTOR. |
| 6347 | 22037215 | Therefore, PI3K may be an important target for the treatment of breast cancer in women with insulin resistance. |
| 6348 | 22037215 | Inhibiting PI3K reduces mammary tumor growth and induces hyperglycemia in a mouse model of insulin resistance and hyperinsulinemia. |
| 6349 | 22037215 | In the MKR mouse model of insulin resistance, we have previously shown increased activation of the phosphatidylinositol 3-kinase (PI3K)/Akt/mTOR pathway in association with accelerated mammary tumor growth. |
| 6350 | 22037215 | NVP-BKM120 treatment decreased phosphorylation of Akt and S6 ribosomal protein (S6rp); no change in Erk1/2 phosphorylation was seen. |
| 6351 | 22037215 | Therefore, we examined whether the oral PI3K/mTOR inhibitor NVP-BEZ235 augmented the tumor suppressing effects of PI3K inhibition. |
| 6352 | 22037215 | We also investigated the effect of targeted PI3K/mTOR inhibition on PI3K/Akt/mTOR and Erk1/2 signaling, and the potential effects on glycemia. |
| 6353 | 22037215 | NVP-BEZ235 suppressed the growth of Met-1 and MCNeuA tumor orthografts, and decreased Akt and S6rp phosphorylation, despite increased Erk1/2 phosphorylation in Met-1 orthografts of MKR mice. |
| 6354 | 22037215 | Overall, the results of this study demonstrated that inhibiting PI3K/Akt/mTOR signaling with the oral agents NVP-BKM120 and NVP-BEZ235 decreased mammary tumor growth in the hyperinsulinemic MKR mouse. |
| 6355 | 22037215 | Inhibiting PI3K alone led to more severe metabolic derangement than inhibiting both PI3K and mTOR. |
| 6356 | 22037215 | Therefore, PI3K may be an important target for the treatment of breast cancer in women with insulin resistance. |
| 6357 | 22037215 | Inhibiting PI3K reduces mammary tumor growth and induces hyperglycemia in a mouse model of insulin resistance and hyperinsulinemia. |
| 6358 | 22037215 | In the MKR mouse model of insulin resistance, we have previously shown increased activation of the phosphatidylinositol 3-kinase (PI3K)/Akt/mTOR pathway in association with accelerated mammary tumor growth. |
| 6359 | 22037215 | NVP-BKM120 treatment decreased phosphorylation of Akt and S6 ribosomal protein (S6rp); no change in Erk1/2 phosphorylation was seen. |
| 6360 | 22037215 | Therefore, we examined whether the oral PI3K/mTOR inhibitor NVP-BEZ235 augmented the tumor suppressing effects of PI3K inhibition. |
| 6361 | 22037215 | We also investigated the effect of targeted PI3K/mTOR inhibition on PI3K/Akt/mTOR and Erk1/2 signaling, and the potential effects on glycemia. |
| 6362 | 22037215 | NVP-BEZ235 suppressed the growth of Met-1 and MCNeuA tumor orthografts, and decreased Akt and S6rp phosphorylation, despite increased Erk1/2 phosphorylation in Met-1 orthografts of MKR mice. |
| 6363 | 22037215 | Overall, the results of this study demonstrated that inhibiting PI3K/Akt/mTOR signaling with the oral agents NVP-BKM120 and NVP-BEZ235 decreased mammary tumor growth in the hyperinsulinemic MKR mouse. |
| 6364 | 22037215 | Inhibiting PI3K alone led to more severe metabolic derangement than inhibiting both PI3K and mTOR. |
| 6365 | 22037215 | Therefore, PI3K may be an important target for the treatment of breast cancer in women with insulin resistance. |
| 6366 | 22037215 | Inhibiting PI3K reduces mammary tumor growth and induces hyperglycemia in a mouse model of insulin resistance and hyperinsulinemia. |
| 6367 | 22037215 | In the MKR mouse model of insulin resistance, we have previously shown increased activation of the phosphatidylinositol 3-kinase (PI3K)/Akt/mTOR pathway in association with accelerated mammary tumor growth. |
| 6368 | 22037215 | NVP-BKM120 treatment decreased phosphorylation of Akt and S6 ribosomal protein (S6rp); no change in Erk1/2 phosphorylation was seen. |
| 6369 | 22037215 | Therefore, we examined whether the oral PI3K/mTOR inhibitor NVP-BEZ235 augmented the tumor suppressing effects of PI3K inhibition. |
| 6370 | 22037215 | We also investigated the effect of targeted PI3K/mTOR inhibition on PI3K/Akt/mTOR and Erk1/2 signaling, and the potential effects on glycemia. |
| 6371 | 22037215 | NVP-BEZ235 suppressed the growth of Met-1 and MCNeuA tumor orthografts, and decreased Akt and S6rp phosphorylation, despite increased Erk1/2 phosphorylation in Met-1 orthografts of MKR mice. |
| 6372 | 22037215 | Overall, the results of this study demonstrated that inhibiting PI3K/Akt/mTOR signaling with the oral agents NVP-BKM120 and NVP-BEZ235 decreased mammary tumor growth in the hyperinsulinemic MKR mouse. |
| 6373 | 22037215 | Inhibiting PI3K alone led to more severe metabolic derangement than inhibiting both PI3K and mTOR. |
| 6374 | 22037215 | Therefore, PI3K may be an important target for the treatment of breast cancer in women with insulin resistance. |
| 6375 | 22037215 | Inhibiting PI3K reduces mammary tumor growth and induces hyperglycemia in a mouse model of insulin resistance and hyperinsulinemia. |
| 6376 | 22037215 | In the MKR mouse model of insulin resistance, we have previously shown increased activation of the phosphatidylinositol 3-kinase (PI3K)/Akt/mTOR pathway in association with accelerated mammary tumor growth. |
| 6377 | 22037215 | NVP-BKM120 treatment decreased phosphorylation of Akt and S6 ribosomal protein (S6rp); no change in Erk1/2 phosphorylation was seen. |
| 6378 | 22037215 | Therefore, we examined whether the oral PI3K/mTOR inhibitor NVP-BEZ235 augmented the tumor suppressing effects of PI3K inhibition. |
| 6379 | 22037215 | We also investigated the effect of targeted PI3K/mTOR inhibition on PI3K/Akt/mTOR and Erk1/2 signaling, and the potential effects on glycemia. |
| 6380 | 22037215 | NVP-BEZ235 suppressed the growth of Met-1 and MCNeuA tumor orthografts, and decreased Akt and S6rp phosphorylation, despite increased Erk1/2 phosphorylation in Met-1 orthografts of MKR mice. |
| 6381 | 22037215 | Overall, the results of this study demonstrated that inhibiting PI3K/Akt/mTOR signaling with the oral agents NVP-BKM120 and NVP-BEZ235 decreased mammary tumor growth in the hyperinsulinemic MKR mouse. |
| 6382 | 22037215 | Inhibiting PI3K alone led to more severe metabolic derangement than inhibiting both PI3K and mTOR. |
| 6383 | 22037215 | Therefore, PI3K may be an important target for the treatment of breast cancer in women with insulin resistance. |
| 6384 | 22037215 | Inhibiting PI3K reduces mammary tumor growth and induces hyperglycemia in a mouse model of insulin resistance and hyperinsulinemia. |
| 6385 | 22037215 | In the MKR mouse model of insulin resistance, we have previously shown increased activation of the phosphatidylinositol 3-kinase (PI3K)/Akt/mTOR pathway in association with accelerated mammary tumor growth. |
| 6386 | 22037215 | NVP-BKM120 treatment decreased phosphorylation of Akt and S6 ribosomal protein (S6rp); no change in Erk1/2 phosphorylation was seen. |
| 6387 | 22037215 | Therefore, we examined whether the oral PI3K/mTOR inhibitor NVP-BEZ235 augmented the tumor suppressing effects of PI3K inhibition. |
| 6388 | 22037215 | We also investigated the effect of targeted PI3K/mTOR inhibition on PI3K/Akt/mTOR and Erk1/2 signaling, and the potential effects on glycemia. |
| 6389 | 22037215 | NVP-BEZ235 suppressed the growth of Met-1 and MCNeuA tumor orthografts, and decreased Akt and S6rp phosphorylation, despite increased Erk1/2 phosphorylation in Met-1 orthografts of MKR mice. |
| 6390 | 22037215 | Overall, the results of this study demonstrated that inhibiting PI3K/Akt/mTOR signaling with the oral agents NVP-BKM120 and NVP-BEZ235 decreased mammary tumor growth in the hyperinsulinemic MKR mouse. |
| 6391 | 22037215 | Inhibiting PI3K alone led to more severe metabolic derangement than inhibiting both PI3K and mTOR. |
| 6392 | 22037215 | Therefore, PI3K may be an important target for the treatment of breast cancer in women with insulin resistance. |
| 6393 | 22056597 | Expression of the peroxisome proliferator-activated receptor-γ2 (PPARγ2) and adipocyte-specific fatty acid binding protein (aP2) mRNAs and the PPARγ2 protein was analyzed in adipocytes using RT-PCR and immunoblotting, respectively. |
| 6394 | 22056597 | Insulin-stimulated protein kinase B (Akt/PKB) phosphorylation was measured in high glucose-induced, insulin-resistant HepG2 cells. |
| 6395 | 22056597 | In high glucose-induced, insulin-resistant HepG2 cells, aromadendrin reversed the inhibition of Akt/PKB phosphorylation in response to insulin, which could be abrogated by pretreatment with LY294002, a phosphatidylinositol 3-kinase (PI3K) inhibitor. |
| 6396 | 22056625 | The phosphoinositide 3-kinase (PI3K) inhibitor, wortmannin, simultaneously regulates Rac1 and Cdc42, which destabilize the podocyte actin cytoskeleton during early DN. |
| 6397 | 22056625 | In this study, in order to evaluate the reno-protective effects of wortmannin in early DN by regulating Rac1 and Cdc42, streptozotocin (STZ)-induced proteinuric renal disease (SPRD) rats were treated with wortmannin. |
| 6398 | 22056625 | Changes in the expression level of nephrin, podocin and Rac1/Cdc42, which is related to actin cytoskeleton in podocytes, by wortmannin administration were confirmed by Western blotting. |
| 6399 | 22056625 | The expression levels of nephrin (79.66 ± 0.02), podocin (87.81 ± 0.03) and Rac1/Cdc42 (86.12 ± 0.02) in the wortmannin group were higher than the expression levels of nephrin (55.32 ± 0.03), podocin (53.40 ± 0.06) and Rac1/Cdc42 (54.05 ± 0.04) in the SPRD group. |
| 6400 | 22056625 | In addition, expression and localization of nephrin, podocin and desmin were confirmed by immunofluorescence. |
| 6401 | 22065862 | Normalizing action of exendin-4 and GLP-1 in the glucose metabolism of extrapancreatic tissues in insulin-resistant and type 2 diabetic states. |
| 6402 | 22065862 | We studied the characteristics of Ex-4 and GLP-1 action, during prolonged treatment, on GLUTs expression (mRNA and protein), glycogen content (GC), glucose transport (GT), glycogen synthase a (GSa), and kinase (PI3K and MAPKs) activity, in liver, muscle, and fat of insulin-resistant (IR, by fructose) and type 2 diabetic (T2D, streptozotocin at birth) rats compared with normal rats. |
| 6403 | 22065862 | In liver, GLP-1 and also Ex-4 normalized the lower than normal Glut2 (Slc2a2) expression and showed a trend to normalize the reduced GC in IR, and GLP-1, like Ex-4, also in T2D, effects mediated by PI3K and MAPKs. |
| 6404 | 22065862 | In skeletal muscle, neither GLP-1 nor Ex-4 modified Glut4 (Slc2a4) expression in either experimental model but showed normalization of reduced GT and GSa, in parallel with the normalization of reduced PI3K activity in T2D and MAPKs in both models. |
| 6405 | 22065862 | In adipose tissue, the altered GLUT4 expression in IR and T2D, along with reduced GT in IR and increased GT in T2D, and with hyperactivated PI3K in both, became normal after GLP-1 and Ex-4 treatment; yet, MAPKs, that were also higher, became normal only after Ex-4 treatment. |
| 6406 | 22065862 | Normalizing action of exendin-4 and GLP-1 in the glucose metabolism of extrapancreatic tissues in insulin-resistant and type 2 diabetic states. |
| 6407 | 22065862 | We studied the characteristics of Ex-4 and GLP-1 action, during prolonged treatment, on GLUTs expression (mRNA and protein), glycogen content (GC), glucose transport (GT), glycogen synthase a (GSa), and kinase (PI3K and MAPKs) activity, in liver, muscle, and fat of insulin-resistant (IR, by fructose) and type 2 diabetic (T2D, streptozotocin at birth) rats compared with normal rats. |
| 6408 | 22065862 | In liver, GLP-1 and also Ex-4 normalized the lower than normal Glut2 (Slc2a2) expression and showed a trend to normalize the reduced GC in IR, and GLP-1, like Ex-4, also in T2D, effects mediated by PI3K and MAPKs. |
| 6409 | 22065862 | In skeletal muscle, neither GLP-1 nor Ex-4 modified Glut4 (Slc2a4) expression in either experimental model but showed normalization of reduced GT and GSa, in parallel with the normalization of reduced PI3K activity in T2D and MAPKs in both models. |
| 6410 | 22065862 | In adipose tissue, the altered GLUT4 expression in IR and T2D, along with reduced GT in IR and increased GT in T2D, and with hyperactivated PI3K in both, became normal after GLP-1 and Ex-4 treatment; yet, MAPKs, that were also higher, became normal only after Ex-4 treatment. |
| 6411 | 22065862 | Normalizing action of exendin-4 and GLP-1 in the glucose metabolism of extrapancreatic tissues in insulin-resistant and type 2 diabetic states. |
| 6412 | 22065862 | We studied the characteristics of Ex-4 and GLP-1 action, during prolonged treatment, on GLUTs expression (mRNA and protein), glycogen content (GC), glucose transport (GT), glycogen synthase a (GSa), and kinase (PI3K and MAPKs) activity, in liver, muscle, and fat of insulin-resistant (IR, by fructose) and type 2 diabetic (T2D, streptozotocin at birth) rats compared with normal rats. |
| 6413 | 22065862 | In liver, GLP-1 and also Ex-4 normalized the lower than normal Glut2 (Slc2a2) expression and showed a trend to normalize the reduced GC in IR, and GLP-1, like Ex-4, also in T2D, effects mediated by PI3K and MAPKs. |
| 6414 | 22065862 | In skeletal muscle, neither GLP-1 nor Ex-4 modified Glut4 (Slc2a4) expression in either experimental model but showed normalization of reduced GT and GSa, in parallel with the normalization of reduced PI3K activity in T2D and MAPKs in both models. |
| 6415 | 22065862 | In adipose tissue, the altered GLUT4 expression in IR and T2D, along with reduced GT in IR and increased GT in T2D, and with hyperactivated PI3K in both, became normal after GLP-1 and Ex-4 treatment; yet, MAPKs, that were also higher, became normal only after Ex-4 treatment. |
| 6416 | 22065862 | Normalizing action of exendin-4 and GLP-1 in the glucose metabolism of extrapancreatic tissues in insulin-resistant and type 2 diabetic states. |
| 6417 | 22065862 | We studied the characteristics of Ex-4 and GLP-1 action, during prolonged treatment, on GLUTs expression (mRNA and protein), glycogen content (GC), glucose transport (GT), glycogen synthase a (GSa), and kinase (PI3K and MAPKs) activity, in liver, muscle, and fat of insulin-resistant (IR, by fructose) and type 2 diabetic (T2D, streptozotocin at birth) rats compared with normal rats. |
| 6418 | 22065862 | In liver, GLP-1 and also Ex-4 normalized the lower than normal Glut2 (Slc2a2) expression and showed a trend to normalize the reduced GC in IR, and GLP-1, like Ex-4, also in T2D, effects mediated by PI3K and MAPKs. |
| 6419 | 22065862 | In skeletal muscle, neither GLP-1 nor Ex-4 modified Glut4 (Slc2a4) expression in either experimental model but showed normalization of reduced GT and GSa, in parallel with the normalization of reduced PI3K activity in T2D and MAPKs in both models. |
| 6420 | 22065862 | In adipose tissue, the altered GLUT4 expression in IR and T2D, along with reduced GT in IR and increased GT in T2D, and with hyperactivated PI3K in both, became normal after GLP-1 and Ex-4 treatment; yet, MAPKs, that were also higher, became normal only after Ex-4 treatment. |
| 6421 | 22127238 | In this review, I have classified these studies according to the intracellular signaling pathways they relate to--phosphatidylinositol 3-kinase, Hedgehog, Calcineurin/NFAT, Epac, and bone morphogenetic protein. |
| 6422 | 22158866 | Inhibition of insulin signaling in endothelial cells by protein kinase C-induced phosphorylation of p85 subunit of phosphatidylinositol 3-kinase (PI3K). |
| 6423 | 22158866 | Protein kinase C (PKC) activation has been reported to inhibit insulin signaling selectively in endothelial cells via the insulin receptor substrate/PI3K/Akt pathway to reduce the activation of endothelial nitric-oxide synthase (eNOS). |
| 6424 | 22158866 | In this study, it was observed that PKC activation differentially inhibited insulin receptor substrate 1/2 (IRS1/2) signaling of insulin's activation of PI3K/eNOS by decreasing only tyrosine phosphorylation of IRS2. |
| 6425 | 22158866 | In addition, PKC activation, by general activator and specifically by angiotensin II, increased the phosphorylation of p85/PI3K, which decreases its association with IRS1 and activation. |
| 6426 | 22158866 | Thr-86 of p85/PI3K was identified to be phosphorylated by PKC activation and confirmed to affect IRS1-mediated activation of Akt/eNOS by insulin and VEGF using a deletion mutant of the Thr-86 region of p85/PI3K. |
| 6427 | 22158866 | Thus, PKC and angiotensin-induced phosphorylation of Thr-86 of p85/PI3K may partially inhibit the activation of PI3K/eNOS by multiple cytokines and contribute to endothelial dysfunction in metabolic disorders. |
| 6428 | 22158866 | Inhibition of insulin signaling in endothelial cells by protein kinase C-induced phosphorylation of p85 subunit of phosphatidylinositol 3-kinase (PI3K). |
| 6429 | 22158866 | Protein kinase C (PKC) activation has been reported to inhibit insulin signaling selectively in endothelial cells via the insulin receptor substrate/PI3K/Akt pathway to reduce the activation of endothelial nitric-oxide synthase (eNOS). |
| 6430 | 22158866 | In this study, it was observed that PKC activation differentially inhibited insulin receptor substrate 1/2 (IRS1/2) signaling of insulin's activation of PI3K/eNOS by decreasing only tyrosine phosphorylation of IRS2. |
| 6431 | 22158866 | In addition, PKC activation, by general activator and specifically by angiotensin II, increased the phosphorylation of p85/PI3K, which decreases its association with IRS1 and activation. |
| 6432 | 22158866 | Thr-86 of p85/PI3K was identified to be phosphorylated by PKC activation and confirmed to affect IRS1-mediated activation of Akt/eNOS by insulin and VEGF using a deletion mutant of the Thr-86 region of p85/PI3K. |
| 6433 | 22158866 | Thus, PKC and angiotensin-induced phosphorylation of Thr-86 of p85/PI3K may partially inhibit the activation of PI3K/eNOS by multiple cytokines and contribute to endothelial dysfunction in metabolic disorders. |
| 6434 | 22158866 | Inhibition of insulin signaling in endothelial cells by protein kinase C-induced phosphorylation of p85 subunit of phosphatidylinositol 3-kinase (PI3K). |
| 6435 | 22158866 | Protein kinase C (PKC) activation has been reported to inhibit insulin signaling selectively in endothelial cells via the insulin receptor substrate/PI3K/Akt pathway to reduce the activation of endothelial nitric-oxide synthase (eNOS). |
| 6436 | 22158866 | In this study, it was observed that PKC activation differentially inhibited insulin receptor substrate 1/2 (IRS1/2) signaling of insulin's activation of PI3K/eNOS by decreasing only tyrosine phosphorylation of IRS2. |
| 6437 | 22158866 | In addition, PKC activation, by general activator and specifically by angiotensin II, increased the phosphorylation of p85/PI3K, which decreases its association with IRS1 and activation. |
| 6438 | 22158866 | Thr-86 of p85/PI3K was identified to be phosphorylated by PKC activation and confirmed to affect IRS1-mediated activation of Akt/eNOS by insulin and VEGF using a deletion mutant of the Thr-86 region of p85/PI3K. |
| 6439 | 22158866 | Thus, PKC and angiotensin-induced phosphorylation of Thr-86 of p85/PI3K may partially inhibit the activation of PI3K/eNOS by multiple cytokines and contribute to endothelial dysfunction in metabolic disorders. |
| 6440 | 22158866 | Inhibition of insulin signaling in endothelial cells by protein kinase C-induced phosphorylation of p85 subunit of phosphatidylinositol 3-kinase (PI3K). |
| 6441 | 22158866 | Protein kinase C (PKC) activation has been reported to inhibit insulin signaling selectively in endothelial cells via the insulin receptor substrate/PI3K/Akt pathway to reduce the activation of endothelial nitric-oxide synthase (eNOS). |
| 6442 | 22158866 | In this study, it was observed that PKC activation differentially inhibited insulin receptor substrate 1/2 (IRS1/2) signaling of insulin's activation of PI3K/eNOS by decreasing only tyrosine phosphorylation of IRS2. |
| 6443 | 22158866 | In addition, PKC activation, by general activator and specifically by angiotensin II, increased the phosphorylation of p85/PI3K, which decreases its association with IRS1 and activation. |
| 6444 | 22158866 | Thr-86 of p85/PI3K was identified to be phosphorylated by PKC activation and confirmed to affect IRS1-mediated activation of Akt/eNOS by insulin and VEGF using a deletion mutant of the Thr-86 region of p85/PI3K. |
| 6445 | 22158866 | Thus, PKC and angiotensin-induced phosphorylation of Thr-86 of p85/PI3K may partially inhibit the activation of PI3K/eNOS by multiple cytokines and contribute to endothelial dysfunction in metabolic disorders. |
| 6446 | 22158866 | Inhibition of insulin signaling in endothelial cells by protein kinase C-induced phosphorylation of p85 subunit of phosphatidylinositol 3-kinase (PI3K). |
| 6447 | 22158866 | Protein kinase C (PKC) activation has been reported to inhibit insulin signaling selectively in endothelial cells via the insulin receptor substrate/PI3K/Akt pathway to reduce the activation of endothelial nitric-oxide synthase (eNOS). |
| 6448 | 22158866 | In this study, it was observed that PKC activation differentially inhibited insulin receptor substrate 1/2 (IRS1/2) signaling of insulin's activation of PI3K/eNOS by decreasing only tyrosine phosphorylation of IRS2. |
| 6449 | 22158866 | In addition, PKC activation, by general activator and specifically by angiotensin II, increased the phosphorylation of p85/PI3K, which decreases its association with IRS1 and activation. |
| 6450 | 22158866 | Thr-86 of p85/PI3K was identified to be phosphorylated by PKC activation and confirmed to affect IRS1-mediated activation of Akt/eNOS by insulin and VEGF using a deletion mutant of the Thr-86 region of p85/PI3K. |
| 6451 | 22158866 | Thus, PKC and angiotensin-induced phosphorylation of Thr-86 of p85/PI3K may partially inhibit the activation of PI3K/eNOS by multiple cytokines and contribute to endothelial dysfunction in metabolic disorders. |
| 6452 | 22158866 | Inhibition of insulin signaling in endothelial cells by protein kinase C-induced phosphorylation of p85 subunit of phosphatidylinositol 3-kinase (PI3K). |
| 6453 | 22158866 | Protein kinase C (PKC) activation has been reported to inhibit insulin signaling selectively in endothelial cells via the insulin receptor substrate/PI3K/Akt pathway to reduce the activation of endothelial nitric-oxide synthase (eNOS). |
| 6454 | 22158866 | In this study, it was observed that PKC activation differentially inhibited insulin receptor substrate 1/2 (IRS1/2) signaling of insulin's activation of PI3K/eNOS by decreasing only tyrosine phosphorylation of IRS2. |
| 6455 | 22158866 | In addition, PKC activation, by general activator and specifically by angiotensin II, increased the phosphorylation of p85/PI3K, which decreases its association with IRS1 and activation. |
| 6456 | 22158866 | Thr-86 of p85/PI3K was identified to be phosphorylated by PKC activation and confirmed to affect IRS1-mediated activation of Akt/eNOS by insulin and VEGF using a deletion mutant of the Thr-86 region of p85/PI3K. |
| 6457 | 22158866 | Thus, PKC and angiotensin-induced phosphorylation of Thr-86 of p85/PI3K may partially inhibit the activation of PI3K/eNOS by multiple cytokines and contribute to endothelial dysfunction in metabolic disorders. |
| 6458 | 22194608 | FTY720 normalizes hyperglycemia by stimulating β-cell in vivo regeneration in db/db mice through regulation of cyclin D3 and p57(KIP2). |
| 6459 | 22194608 | Finally, islets from the treated mice exhibited a significant decrease in the level of cyclin-dependent kinase inhibitor p57(KIP2) and an increase in the level of cyclin D3 as compared with those of untreated mice, which could be reversed by the inhibition of phosphatidylinositol 3-kinase (PI3K). |
| 6460 | 22194608 | Our findings reveal a novel network that controls β-cell regeneration in the obesity-diabetes setting by regulating cyclin D3 and p57(KIP2) expression through the S1P signaling pathway. |
| 6461 | 22215652 | Insulin-stimulated PI3K activity in skeletal muscle and adipose tissue of DIO mice was significantly reduced ∼50-65%, but this was restored completely by INT131 therapy. |
| 6462 | 22215652 | The INT131 effects on PI3K activity are most likely due to increased IRS-1 tyrosine phosphorylation. |
| 6463 | 22215652 | Concurrently, insulin-mediated Akt phosphorylation also increased after INT131 treatment in DIO mice. |
| 6464 | 22215652 | These data suggest that a newly developed insulin-sensitizing agent, INT131, normalizes obesity-related defects in insulin action on PI3K signaling in insulin target tissues by a mechanism involved in glycemic control. |
| 6465 | 22215652 | Insulin-stimulated PI3K activity in skeletal muscle and adipose tissue of DIO mice was significantly reduced ∼50-65%, but this was restored completely by INT131 therapy. |
| 6466 | 22215652 | The INT131 effects on PI3K activity are most likely due to increased IRS-1 tyrosine phosphorylation. |
| 6467 | 22215652 | Concurrently, insulin-mediated Akt phosphorylation also increased after INT131 treatment in DIO mice. |
| 6468 | 22215652 | These data suggest that a newly developed insulin-sensitizing agent, INT131, normalizes obesity-related defects in insulin action on PI3K signaling in insulin target tissues by a mechanism involved in glycemic control. |
| 6469 | 22215652 | Insulin-stimulated PI3K activity in skeletal muscle and adipose tissue of DIO mice was significantly reduced ∼50-65%, but this was restored completely by INT131 therapy. |
| 6470 | 22215652 | The INT131 effects on PI3K activity are most likely due to increased IRS-1 tyrosine phosphorylation. |
| 6471 | 22215652 | Concurrently, insulin-mediated Akt phosphorylation also increased after INT131 treatment in DIO mice. |
| 6472 | 22215652 | These data suggest that a newly developed insulin-sensitizing agent, INT131, normalizes obesity-related defects in insulin action on PI3K signaling in insulin target tissues by a mechanism involved in glycemic control. |
| 6473 | 22233681 | PI3K/AKT, MAPK and AMPK signalling: protein kinases in glucose homeostasis. |
| 6474 | 22233681 | Deregulation of the phosphoinositide-3-kinase (PI3K)/v-akt murine thymoma viral oncogene homologue (AKT), mitogen-activated protein kinase (MAPK) and AMP-activated protein kinase (AMPK) pathways, which are essential for glucose homeostasis, often results in obesity and diabetes. |
| 6475 | 22233681 | By contrast, therapies based on the inhibition of the PI3K/AKT and MAPK pathways are already successful in the treatment of diverse cancer types and inflammatory diseases. |
| 6476 | 22233681 | This contradiction prompted us to review the signal transduction mechanisms of PI3K/AKT, MAPK and AMPK and their roles in glucose homeostasis, and we also discuss current clinical implications. |
| 6477 | 22233681 | PI3K/AKT, MAPK and AMPK signalling: protein kinases in glucose homeostasis. |
| 6478 | 22233681 | Deregulation of the phosphoinositide-3-kinase (PI3K)/v-akt murine thymoma viral oncogene homologue (AKT), mitogen-activated protein kinase (MAPK) and AMP-activated protein kinase (AMPK) pathways, which are essential for glucose homeostasis, often results in obesity and diabetes. |
| 6479 | 22233681 | By contrast, therapies based on the inhibition of the PI3K/AKT and MAPK pathways are already successful in the treatment of diverse cancer types and inflammatory diseases. |
| 6480 | 22233681 | This contradiction prompted us to review the signal transduction mechanisms of PI3K/AKT, MAPK and AMPK and their roles in glucose homeostasis, and we also discuss current clinical implications. |
| 6481 | 22233681 | PI3K/AKT, MAPK and AMPK signalling: protein kinases in glucose homeostasis. |
| 6482 | 22233681 | Deregulation of the phosphoinositide-3-kinase (PI3K)/v-akt murine thymoma viral oncogene homologue (AKT), mitogen-activated protein kinase (MAPK) and AMP-activated protein kinase (AMPK) pathways, which are essential for glucose homeostasis, often results in obesity and diabetes. |
| 6483 | 22233681 | By contrast, therapies based on the inhibition of the PI3K/AKT and MAPK pathways are already successful in the treatment of diverse cancer types and inflammatory diseases. |
| 6484 | 22233681 | This contradiction prompted us to review the signal transduction mechanisms of PI3K/AKT, MAPK and AMPK and their roles in glucose homeostasis, and we also discuss current clinical implications. |
| 6485 | 22233681 | PI3K/AKT, MAPK and AMPK signalling: protein kinases in glucose homeostasis. |
| 6486 | 22233681 | Deregulation of the phosphoinositide-3-kinase (PI3K)/v-akt murine thymoma viral oncogene homologue (AKT), mitogen-activated protein kinase (MAPK) and AMP-activated protein kinase (AMPK) pathways, which are essential for glucose homeostasis, often results in obesity and diabetes. |
| 6487 | 22233681 | By contrast, therapies based on the inhibition of the PI3K/AKT and MAPK pathways are already successful in the treatment of diverse cancer types and inflammatory diseases. |
| 6488 | 22233681 | This contradiction prompted us to review the signal transduction mechanisms of PI3K/AKT, MAPK and AMPK and their roles in glucose homeostasis, and we also discuss current clinical implications. |
| 6489 | 22245457 | In adipose tissue and muscle, IR results in decreased insulin signaling, primarily affecting downstream phosphatidylinositol 3-kinase (PI3K)/Akt signaling. |
| 6490 | 22272041 | Enhanced Urinary Bladder, Liver and Colon Carcinogenesis in Zucker Diabetic Fatty Rats in a Multiorgan Carcinogenesis Bioassay: Evidence for Mechanisms Involving Activation of PI3K Signaling and Impairment of p53 on Urinary Bladder Carcinogenesis. |
| 6491 | 22272041 | Elevated insulin and leptin and decreased adiponectin levels in the serum may be responsible for the high susceptibility of type 2 diabetes mellitus model rats to carcinogenesis in these organs. |
| 6492 | 22272041 | Possible mechanisms of increased susceptibility of diabetic rats to bladder carcinogenesis could be activation of the PI3K pathway and suppression of p53 in the urothelium in consequence of the above serum protein alterations. |
| 6493 | 22272041 | Enhanced Urinary Bladder, Liver and Colon Carcinogenesis in Zucker Diabetic Fatty Rats in a Multiorgan Carcinogenesis Bioassay: Evidence for Mechanisms Involving Activation of PI3K Signaling and Impairment of p53 on Urinary Bladder Carcinogenesis. |
| 6494 | 22272041 | Elevated insulin and leptin and decreased adiponectin levels in the serum may be responsible for the high susceptibility of type 2 diabetes mellitus model rats to carcinogenesis in these organs. |
| 6495 | 22272041 | Possible mechanisms of increased susceptibility of diabetic rats to bladder carcinogenesis could be activation of the PI3K pathway and suppression of p53 in the urothelium in consequence of the above serum protein alterations. |
| 6496 | 22285432 | In this study, we attempt to reveal how sodium arsenite (iAs) could induce stress mediated impaired insulin signaling in mice and if an isolated active fraction of ginger, [6]-gingerol could attenuate the iAs intoxicated hyperglycemic condition of mice and bring about improvement in their impaired insulin signaling. [6]-Gingerol treatment reduced elevated blood glucose level and oxidative stress by enhancing activity of super oxide dismutase (SOD), catalase, glutathione peroxidase (GPx) and GSH. [6]-Gingerol also helped in increasing plasma insulin level, brought down after iAs exposure. iAs treatment to primary cell culture of β-cells and hepatocytes in vitro produced cyto-degenerative effect and accumulated reactive oxygen species (ROS) in pancreatic β-cells and hepatocytes of mice. [6]-Gingerol appeared to inhibit/intervene iAs induced cyto-degeneration of pancreatic β-cells and hepatocytes, helped in scavenging the free radicals. |
| 6497 | 22285432 | The over-expression of TNFα and IL6 in iAs intoxicated mice was down-regulated by [6]-gingerol treatment. iAs intoxication reduced expression levels of GLUT4, IRS-1, IRS-2, PI3K, AKT, PPARγ signaling molecules; [6]-gingerol mediated its action through enhancing the expressions of these signaling molecules, both at protein and mRNA levels. |
| 6498 | 22288306 | Effect of insulin in combination with selenium on Irs/PI3K-mediated GLUT4 expression in cardiac muscle of diabetic rats. |
| 6499 | 22298456 | The present results suggest that the antihyperglycemic action of MA is mediated by increasing glucose uptake via the activation of PI3-K signaling pathway and translocation of GLUT4 to the plasma membrane. |
| 6500 | 22308370 | Glucose activates free fatty acid receptor 1 gene transcription via phosphatidylinositol-3-kinase-dependent O-GlcNAcylation of pancreas-duodenum homeobox-1. |
| 6501 | 22308370 | The G protein-coupled free fatty acid receptor-1 (FFA1/GPR40) plays a major role in the regulation of insulin secretion by fatty acids. |
| 6502 | 22308370 | GPR40 is considered a potential therapeutic target to enhance insulin secretion in type 2 diabetes; however, its mode of regulation is essentially unknown. |
| 6503 | 22308370 | We observed that glucose stimulates GPR40 gene transcription in pancreatic β-cells via increased binding of pancreas-duodenum homeobox-1 (Pdx-1) to the A-box in the HR2 region of the GPR40 promoter. |
| 6504 | 22308370 | Mutation of the Pdx-1 binding site within the HR2 abolishes glucose activation of GPR40 promoter activity. |
| 6505 | 22308370 | The stimulation of GPR40 expression and Pdx-1 binding to the HR2 in response to glucose are mimicked by N-acetyl glucosamine, an intermediate of the hexosamine biosynthesis pathway, and involve PI3K-dependent O-GlcNAcylation of Pdx-1 in the nucleus. |
| 6506 | 22308370 | We demonstrate that O-GlcNAc transferase (OGT) interacts with the product of the PI3K reaction, phosphatidylinositol 3,4,5-trisphosphate (PIP(3)), in the nucleus. |
| 6507 | 22308370 | This interaction enables OGT to catalyze O-GlcNAcylation of nuclear proteins, including Pdx-1. |
| 6508 | 22308370 | We conclude that glucose stimulates GPR40 gene expression at the transcriptional level through Pdx-1 binding to the HR2 region and via a signaling cascade that involves an interaction between OGT and PIP(3) at the nuclear membrane. |
| 6509 | 22308370 | Glucose activates free fatty acid receptor 1 gene transcription via phosphatidylinositol-3-kinase-dependent O-GlcNAcylation of pancreas-duodenum homeobox-1. |
| 6510 | 22308370 | The G protein-coupled free fatty acid receptor-1 (FFA1/GPR40) plays a major role in the regulation of insulin secretion by fatty acids. |
| 6511 | 22308370 | GPR40 is considered a potential therapeutic target to enhance insulin secretion in type 2 diabetes; however, its mode of regulation is essentially unknown. |
| 6512 | 22308370 | We observed that glucose stimulates GPR40 gene transcription in pancreatic β-cells via increased binding of pancreas-duodenum homeobox-1 (Pdx-1) to the A-box in the HR2 region of the GPR40 promoter. |
| 6513 | 22308370 | Mutation of the Pdx-1 binding site within the HR2 abolishes glucose activation of GPR40 promoter activity. |
| 6514 | 22308370 | The stimulation of GPR40 expression and Pdx-1 binding to the HR2 in response to glucose are mimicked by N-acetyl glucosamine, an intermediate of the hexosamine biosynthesis pathway, and involve PI3K-dependent O-GlcNAcylation of Pdx-1 in the nucleus. |
| 6515 | 22308370 | We demonstrate that O-GlcNAc transferase (OGT) interacts with the product of the PI3K reaction, phosphatidylinositol 3,4,5-trisphosphate (PIP(3)), in the nucleus. |
| 6516 | 22308370 | This interaction enables OGT to catalyze O-GlcNAcylation of nuclear proteins, including Pdx-1. |
| 6517 | 22308370 | We conclude that glucose stimulates GPR40 gene expression at the transcriptional level through Pdx-1 binding to the HR2 region and via a signaling cascade that involves an interaction between OGT and PIP(3) at the nuclear membrane. |
| 6518 | 22308370 | Glucose activates free fatty acid receptor 1 gene transcription via phosphatidylinositol-3-kinase-dependent O-GlcNAcylation of pancreas-duodenum homeobox-1. |
| 6519 | 22308370 | The G protein-coupled free fatty acid receptor-1 (FFA1/GPR40) plays a major role in the regulation of insulin secretion by fatty acids. |
| 6520 | 22308370 | GPR40 is considered a potential therapeutic target to enhance insulin secretion in type 2 diabetes; however, its mode of regulation is essentially unknown. |
| 6521 | 22308370 | We observed that glucose stimulates GPR40 gene transcription in pancreatic β-cells via increased binding of pancreas-duodenum homeobox-1 (Pdx-1) to the A-box in the HR2 region of the GPR40 promoter. |
| 6522 | 22308370 | Mutation of the Pdx-1 binding site within the HR2 abolishes glucose activation of GPR40 promoter activity. |
| 6523 | 22308370 | The stimulation of GPR40 expression and Pdx-1 binding to the HR2 in response to glucose are mimicked by N-acetyl glucosamine, an intermediate of the hexosamine biosynthesis pathway, and involve PI3K-dependent O-GlcNAcylation of Pdx-1 in the nucleus. |
| 6524 | 22308370 | We demonstrate that O-GlcNAc transferase (OGT) interacts with the product of the PI3K reaction, phosphatidylinositol 3,4,5-trisphosphate (PIP(3)), in the nucleus. |
| 6525 | 22308370 | This interaction enables OGT to catalyze O-GlcNAcylation of nuclear proteins, including Pdx-1. |
| 6526 | 22308370 | We conclude that glucose stimulates GPR40 gene expression at the transcriptional level through Pdx-1 binding to the HR2 region and via a signaling cascade that involves an interaction between OGT and PIP(3) at the nuclear membrane. |
| 6527 | 22341695 | Exercise training enhances cardiac IGFI-R/PI3K/Akt and Bcl-2 family associated pro-survival pathways in streptozotocin-induced diabetic rats. |
| 6528 | 22357959 | Candesartan cilexetil improves angiotensin II type 2 receptor-mediated neurite outgrowth via the PI3K-Akt pathway in fructose-induced insulin-resistant rats. |
| 6529 | 22357959 | We found that the FDR developed insulin resistance and downregulated both AT(2)R neuronal function and phosphorylated Akt expression in dorsal root ganglia (DRG) neurons. |
| 6530 | 22357959 | PI3K activation increased AT(2)R-mediated neurite outgrowth and phosphorylated Akt expression in FDR DRG cells. |
| 6531 | 22357959 | These results suggest that the decrease of AT(2)R-mediated neurite outgrowth in FDRs is likely to be the result of decreased PI3K-dependent Akt activation. |
| 6532 | 22357959 | Candesartan improved AT(2)R neuronal function and Akt phosphorylation, which were associated with sensory nerve defects and insulin sensitivity in the FDR. |
| 6533 | 22357959 | Candesartan cilexetil improves angiotensin II type 2 receptor-mediated neurite outgrowth via the PI3K-Akt pathway in fructose-induced insulin-resistant rats. |
| 6534 | 22357959 | We found that the FDR developed insulin resistance and downregulated both AT(2)R neuronal function and phosphorylated Akt expression in dorsal root ganglia (DRG) neurons. |
| 6535 | 22357959 | PI3K activation increased AT(2)R-mediated neurite outgrowth and phosphorylated Akt expression in FDR DRG cells. |
| 6536 | 22357959 | These results suggest that the decrease of AT(2)R-mediated neurite outgrowth in FDRs is likely to be the result of decreased PI3K-dependent Akt activation. |
| 6537 | 22357959 | Candesartan improved AT(2)R neuronal function and Akt phosphorylation, which were associated with sensory nerve defects and insulin sensitivity in the FDR. |
| 6538 | 22357965 | Increasing circulating IGFBP1 levels improves insulin sensitivity, promotes nitric oxide production, lowers blood pressure, and protects against atherosclerosis. |
| 6539 | 22357965 | Low concentrations of insulin-like growth factor (IGF) binding protein-1 (IGFBP1) are associated with insulin resistance, diabetes, and cardiovascular disease. |
| 6540 | 22357965 | Metabolic and vascular phenotype were examined in response to human IGFBP1 overexpression in mice with diet-induced obesity, mice heterozygous for deletion of insulin receptors (IR(+/-)), and ApoE(-/-) mice. |
| 6541 | 22357965 | Overexpression of hIGFBP1 in obese mice reduced blood pressure, improved insulin sensitivity, and increased insulin-stimulated NO generation. |
| 6542 | 22357965 | In nonobese IR(+/-) mice, overexpression of hIGFBP1 reduced blood pressure and improved insulin-stimulated NO generation. hIGFBP1 induced vasodilatation independently of IGF and increased endothelial NO synthase (eNOS) activity in arterial segments ex vivo, while in endothelial cells, hIGFBP1 increased eNOS Ser(1177) phosphorylation via phosphatidylinositol 3-kinase signaling. |
| 6543 | 22357965 | Finally, in ApoE(-/-) mice, overexpression of hIGFBP1 reduced atherosclerosis. |
| 6544 | 22357965 | These favorable effects of hIGFBP1 on insulin sensitivity, blood pressure, NO production, and atherosclerosis suggest that increasing IGFBP1 concentration may be a novel approach to prevent cardiovascular disease in the setting of insulin resistance and diabetes. |
| 6545 | 22362362 | An indolent non-healing wound and insulin and/or insulin-like growth factor (IGF1) resistance are cardinal features of diabetes, inflammation and hypercortisolemia. |
| 6546 | 22362362 | Do the various triggers that induce insulin and/or IGF1 resistance and retard wound healing act through a common mechanism? |
| 6547 | 22362362 | In normal fibroblasts, IGF1 initiated a strong degree of phosphorylation of insulin receptor substrate 1 (IRS1) (Tyr612) and Akt (Ser473), concomitantly with increased PI3K activity. |
| 6548 | 22362362 | The above-mentioned defects were reflected functionally by attenuation in IGF1-dependent stimulation of key fibroblast functions, including collagen synthesis and cell proliferation, migration and contraction. |
| 6549 | 22362362 | The ROS suppressors EUK-134 and α-lipoic acid, or small interfering RNA (siRNA)-mediated silencing of JNK expression, restored IGF1 sensitivity both in vitro and in vivo, and also ameliorated the impairment in IGF1-mediated wound responses during diabetes, inflammation and hypercortisolemia. |
| 6550 | 22367460 | Bradykinin prevents the apoptosis of NIT-1 cells induced by TNF-α via the PI3K/Akt and MAPK signaling pathways. |
| 6551 | 22367460 | These effects were associated with upregulation of Bcl-2 and Bcl-xL protein expression levels as well as with downregulation of Bax expression levels via the activation of the mitogen-activated protein kinase and PI3K/Akt signaling pathways. |
| 6552 | 22367460 | Bradykinin prevents the apoptosis of NIT-1 cells induced by TNF-α via the PI3K/Akt and MAPK signaling pathways. |
| 6553 | 22367460 | These effects were associated with upregulation of Bcl-2 and Bcl-xL protein expression levels as well as with downregulation of Bax expression levels via the activation of the mitogen-activated protein kinase and PI3K/Akt signaling pathways. |
| 6554 | 22387882 | Alterations in insulin signaling in primary mammalian adipocytes were determined by the phosphorylation of Akt, a critical insulin signaling intermediate. |
| 6555 | 22387882 | Treatment of primary murine adipose tissue in vitro with 100nM TF for 48h markedly attenuated acute insulin-stimulated Akt phosphorylation in a strain- and species-independent fashion. |
| 6556 | 22387882 | A similar TF-induced reduction in insulin-stimulated Akt phosphorylation was observed in primary human subcutaneous adipose tissue. |
| 6557 | 22387882 | In contrast, insulin receptor-β, phosphatidylinositol 3-kinase, and Akt expression were unchanged, indicating a specific abrogation of insulin signaling. |
| 6558 | 22387882 | Additionally, TF-treated adipocytes exhibited altered endocrine function with a reduction in both basal and insulin-stimulated leptin secretion. |
| 6559 | 22387882 | These studies demonstrate that TF induces cellular insulin resistance in primary murine and human adipocytes through a reduction of IRS-1 expression and protein stability, raising concern about the potential for this fungicide to disrupt metabolism and thereby contribute to the pathogenesis of diabetes. |
| 6560 | 22412912 | GLUT 4 translocation, phosphorylation of AMPK and Akt, AMPK activity, and association of IRS-1 and PI3K were investigated in the presence of CGA. |
| 6561 | 22412912 | Consistent with these results, CGA was found to phosphorylate AMPK and ACC, consistent with the result of increased AMPK activities. |
| 6562 | 22412912 | CGA did not appear to enhance association of IRS-1 with p85. |
| 6563 | 22426420 | CITED2 links hormonal signaling to PGC-1α acetylation in the regulation of gluconeogenesis. |
| 6564 | 22426420 | Hormonal and nutrient regulation of metabolic adaptation during fasting is mediated predominantly by the transcriptional coactivator peroxisome proliferative activated receptor γ coactivator 1α (PGC-1α) in concert with various other transcriptional regulators. |
| 6565 | 22426420 | Here we show that CITED2 is required for the regulation of hepatic gluconeogenesis through PGC-1α. |
| 6566 | 22426420 | The abundance of CITED2 was increased in the livers of mice by fasting and in cultured hepatocytes by glucagon-cAMP-protein kinase A (PKA) signaling, and the amount of CITED2 in liver was higher in mice with type 2 diabetes than in non-diabetic mice. |
| 6567 | 22426420 | CITED2 inhibited the acetylation of PGC-1α by blocking its interaction with the acetyltransferase general control of amino acid synthesis 5-like 2 (GCN5). |
| 6568 | 22426420 | The interaction of CITED2 with GCN5 was disrupted by insulin in a manner that was dependent on phosphoinositide 3-kinase (PI3K)-thymoma viral proto-oncogene (Akt) signaling. |
| 6569 | 22426420 | Our results show that CITED2 functions as a transducer of glucagon and insulin signaling in the regulation of PGC-1α activity that is associated with the transcriptional control of gluconeogenesis and that this function is mediated through the modulation of GCN5-dependent PGC-1α acetylation. |
| 6570 | 22492526 | In vivo and in vitro insulin restored TRPV1 activity in a phosphatidylinositol 3-kinase/protein kinase C-dependent manner and stimulated TRPV1 receptor trafficking to the plasma membrane. |
| 6571 | 22509328 | RLIP76 regulates PI3K/Akt signaling and chemo-radiotherapy resistance in pancreatic cancer. |
| 6572 | 22547676 | Transient neonatal diabetes mellitus gene Zac1 impairs insulin secretion in mice through Rasgrf1. |
| 6573 | 22547676 | The biallelic expression of the imprinted gene ZAC1/PLAGL1 underlies ≈ 60% of all cases of transient neonatal diabetes mellitus (TNDM) that present with low perinatal insulin secretion. |
| 6574 | 22547676 | Here, we identified the guanine nucleotide exchange factor Rasgrf1 as a direct Zac1/Plagl1 target gene in murine β cells. |
| 6575 | 22547676 | Doubling Zac1 expression reduced Rasgrf1 expression, the stimulus-induced activation of mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K) pathways, and, ultimately, insulin secretion. |
| 6576 | 22547676 | In contrast, Zac1 expression did not interfere with the signaling of the glucagon-like peptide 1 receptor (GLP-1R), and the GLP-1 analog liraglutide improved hyperglycemia in transplanted experimental diabetic mice. |
| 6577 | 22620683 | Further study demonstrated that LA upregulated Pdx1 and Bcl2 gene expression, reduced Bax gene expression, and promoted phosphorylation of Akt in HIT-T15 cells treated with high glucose. |
| 6578 | 22620683 | However, inhibition of Akt by PI3K/AKT antagonist LY294002 only slightly reversed the anti-apoptosis effect of LA and mildly decreased the gene expression level of Pdx1 (P > 0.05). |
| 6579 | 22654559 | The MAPK/ERK (mitogen-activated protein kinase/extracellular signal- regulated kinase signaling pathway) and PI3K/Akt (lipid kinase phoshoinositide-3-kinase signaling pathway) play an important role in transmission of cell signals through transduction systems as ligands, transmembrane receptors and cytoplasmic secondary messengers to cell nucleus, where they influence the expression of genes that regulate important cellular processes: cell growth, proliferation and apoptosis. |
| 6580 | 22654559 | The genes, coding the signaling cascade proteins (RET, RAS, BRAF, PI3K, PTEN, AKT), are mutated or aberrantly expressed in thyroid cancer derived from follicular thyroid cell. |
| 6581 | 22654559 | Genetic and epigenetic alternations, concerning MAPK/ERK and PI3K/Akt signaling pathways, contribute to their activation and interaction in consequence of malignant follicular cell transformation. |
| 6582 | 22654559 | The MAPK/ERK (mitogen-activated protein kinase/extracellular signal- regulated kinase signaling pathway) and PI3K/Akt (lipid kinase phoshoinositide-3-kinase signaling pathway) play an important role in transmission of cell signals through transduction systems as ligands, transmembrane receptors and cytoplasmic secondary messengers to cell nucleus, where they influence the expression of genes that regulate important cellular processes: cell growth, proliferation and apoptosis. |
| 6583 | 22654559 | The genes, coding the signaling cascade proteins (RET, RAS, BRAF, PI3K, PTEN, AKT), are mutated or aberrantly expressed in thyroid cancer derived from follicular thyroid cell. |
| 6584 | 22654559 | Genetic and epigenetic alternations, concerning MAPK/ERK and PI3K/Akt signaling pathways, contribute to their activation and interaction in consequence of malignant follicular cell transformation. |
| 6585 | 22654559 | The MAPK/ERK (mitogen-activated protein kinase/extracellular signal- regulated kinase signaling pathway) and PI3K/Akt (lipid kinase phoshoinositide-3-kinase signaling pathway) play an important role in transmission of cell signals through transduction systems as ligands, transmembrane receptors and cytoplasmic secondary messengers to cell nucleus, where they influence the expression of genes that regulate important cellular processes: cell growth, proliferation and apoptosis. |
| 6586 | 22654559 | The genes, coding the signaling cascade proteins (RET, RAS, BRAF, PI3K, PTEN, AKT), are mutated or aberrantly expressed in thyroid cancer derived from follicular thyroid cell. |
| 6587 | 22654559 | Genetic and epigenetic alternations, concerning MAPK/ERK and PI3K/Akt signaling pathways, contribute to their activation and interaction in consequence of malignant follicular cell transformation. |
| 6588 | 22654843 | In neurons, as in a variety of other cell types, the enzyme phosphatidylinositol-3-kinase (PI3K) is a key intermediate that is common to the signaling pathways of a number of peripheral metabolic cues, including insulin and leptin, which are well known to regulate both metabolic and reproductive functions. |
| 6589 | 22654843 | Impaired hypothalamic insulin and leptin receptor signaling is thought to be at the core of reproductive disorders associated with metabolic dysfunction. |
| 6590 | 22654843 | While low levels of leptin and insulin characterize states of negative energy balance, prolonged nutrient excess is associated with insulin and leptin resistance. |
| 6591 | 22654843 | Metabolic models known to alter GnRH/LH release such as diabetes, diet-induced obesity, and caloric restriction are also accompanied by impairment of PI3K signaling in insulin and leptin sensitive tissues including the hypothalamus. |
| 6592 | 22654843 | In neurons, as in a variety of other cell types, the enzyme phosphatidylinositol-3-kinase (PI3K) is a key intermediate that is common to the signaling pathways of a number of peripheral metabolic cues, including insulin and leptin, which are well known to regulate both metabolic and reproductive functions. |
| 6593 | 22654843 | Impaired hypothalamic insulin and leptin receptor signaling is thought to be at the core of reproductive disorders associated with metabolic dysfunction. |
| 6594 | 22654843 | While low levels of leptin and insulin characterize states of negative energy balance, prolonged nutrient excess is associated with insulin and leptin resistance. |
| 6595 | 22654843 | Metabolic models known to alter GnRH/LH release such as diabetes, diet-induced obesity, and caloric restriction are also accompanied by impairment of PI3K signaling in insulin and leptin sensitive tissues including the hypothalamus. |
| 6596 | 22661254 | As the major anabolic hormone in mammals, insulin stimulates protein synthesis partially through the activation of the PI3K/Akt/mTOR pathway, playing fundamental roles in neuronal development, synaptic plasticity and memory. |
| 6597 | 22661511 | Treatment with phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) inhibitor increased injury demonstrated by increased LDH release in ARTg, WT, and ARKO hearts and in Ad-hAR-expressing HL-1 cells. |
| 6598 | 22663897 | CUMS procedure significantly up-regulated corticotropin-releasing factor (CRF)-related peptide urocortin 2 expression and elevated cAMP production, resulting in over-expression of suppressor of cytokine signaling 3 (SOCS3) in hypothalamic arcuate nucleus (ARC) of rats. |
| 6599 | 22663897 | Furthermore, SOCS3 activation blocked insulin signaling pathway through the suppression of insulin receptor substrate 2 (IRS2) phosphotyrosine and phosphatidylinositol-3-kinase (PI3-K) activation in hypothalamic ARC of CUMS rats after high-level of insulin stimulation. |
| 6600 | 22684034 | Metabolic actions of angiotensin II and insulin: a microvascular endothelial balancing act. |
| 6601 | 22684034 | The balance between NO-dependent vasodilator actions and endothelin-1-dependent vasoconstrictor actions of insulin is regulated by phosphatidylinositol 3-kinase-dependent (PI3K)--and mitogen-activated protein kinase (MAPK)-dependent signaling in vascular endothelium, respectively. |
| 6602 | 22684034 | Angiotensin II acting on AT₂ receptor increases capillary blood flow to increase insulin-mediated glucose disposal. |
| 6603 | 22684034 | Insulin-resistant states are characterized by dysregulated local renin-angiotensin-aldosterone system (RAAS). |
| 6604 | 22684034 | Under insulin-resistant conditions, pathway-specific impairment in PI3K-dependent signaling may cause imbalance between production of NO and secretion of endothelin-1, leading to decreased blood flow, which worsens insulin resistance. |
| 6605 | 22684034 | In the present review, we discuss molecular mechanisms in the endothelium underlying microvascular and metabolic actions of insulin and Angiotensin II, the mechanistic basis for microvascular endothelial dysfunction and insulin resistance in RAAS dysregulated clinical states, and the rationale for therapeutic strategies that restore the balance in vasodilator and constrictor actions of insulin and Angiotensin II in the microvasculature. |
| 6606 | 22684034 | Metabolic actions of angiotensin II and insulin: a microvascular endothelial balancing act. |
| 6607 | 22684034 | The balance between NO-dependent vasodilator actions and endothelin-1-dependent vasoconstrictor actions of insulin is regulated by phosphatidylinositol 3-kinase-dependent (PI3K)--and mitogen-activated protein kinase (MAPK)-dependent signaling in vascular endothelium, respectively. |
| 6608 | 22684034 | Angiotensin II acting on AT₂ receptor increases capillary blood flow to increase insulin-mediated glucose disposal. |
| 6609 | 22684034 | Insulin-resistant states are characterized by dysregulated local renin-angiotensin-aldosterone system (RAAS). |
| 6610 | 22684034 | Under insulin-resistant conditions, pathway-specific impairment in PI3K-dependent signaling may cause imbalance between production of NO and secretion of endothelin-1, leading to decreased blood flow, which worsens insulin resistance. |
| 6611 | 22684034 | In the present review, we discuss molecular mechanisms in the endothelium underlying microvascular and metabolic actions of insulin and Angiotensin II, the mechanistic basis for microvascular endothelial dysfunction and insulin resistance in RAAS dysregulated clinical states, and the rationale for therapeutic strategies that restore the balance in vasodilator and constrictor actions of insulin and Angiotensin II in the microvasculature. |
| 6612 | 22698915 | Attenuated Pik3r1 expression prevents insulin resistance and adipose tissue macrophage accumulation in diet-induced obese mice. |
| 6613 | 22698915 | Here, we find that the Pik3r1 regulatory subunits (i.e., p85α/p55α/p50α) are highly induced in AT from high-fat diet-fed obese mice, concurrent with insulin resistance. |
| 6614 | 22698915 | Global heterozygous deletion of the Pik3r1 regulatory subunits (αHZ), but not knockout of Pik3r2 (p85β), preserves whole-body, AT, and skeletal muscle insulin sensitivity, despite severe obesity. |
| 6615 | 22698915 | Moreover, ATM accumulation, proinflammatory gene expression, and ex vivo chemokine secretion in obese αHZ mice are markedly reduced despite endoplasmic reticulum (ER) stress, hypoxia, adipocyte hypertrophy, and Jun NH(2)-terminal kinase activation. |
| 6616 | 22698915 | Taken together, these studies demonstrate that Pik3r1 expression plays a critical role in mediating AT insulin sensitivity and, more so, suggest that reduced PI3K activity is a key step in the initiation and propagation of the inflammatory response in obese AT. |
| 6617 | 22706082 | Unlike high-dose LPS, low-dose LPS does not induce robust activation of NF-κB, MAPKs, PI3K, or anti-inflammatory mediators. |
| 6618 | 22706082 | Instead, low-dose LPS induces activating transcription factor 2 through Toll-interacting protein-mediated generation of mitochondrial reactive oxygen species, allowing mild induction of proinflammatory mediators. |
| 6619 | 22814999 | Link between the renin-angiotensin system and insulin resistance: implications for cardiovascular disease. |
| 6620 | 22814999 | Insulin activation of the phosphatidylinositol-3-kinase (PI3K) pathway promotes nitric oxide (NO) production in the endothelium and glucose uptake in insulin-sensitive tissues. |
| 6621 | 22814999 | Angiotensin (Ang) II inhibits insulin-mediated PI3K pathway activation, thereby impairing endothelial NO production and Glut-4 translocation in insulin-sensitive tissues, which results in vascular and systemic insulin resistance, respectively. |
| 6622 | 22814999 | On the other hand, Ang II enhances insulin-mediated activation of the mitogen-activated protein kinase (MAPK) pathway, which leads to vasoconstriction and pathologic vascular cellular growth. |
| 6623 | 22814999 | Therefore, the interaction of Ang II with insulin signaling is fully operative not only in insulin-sensitive tissues but also in CV tissues, thereby linking insulin resistance and CV disease. |
| 6624 | 22814999 | Link between the renin-angiotensin system and insulin resistance: implications for cardiovascular disease. |
| 6625 | 22814999 | Insulin activation of the phosphatidylinositol-3-kinase (PI3K) pathway promotes nitric oxide (NO) production in the endothelium and glucose uptake in insulin-sensitive tissues. |
| 6626 | 22814999 | Angiotensin (Ang) II inhibits insulin-mediated PI3K pathway activation, thereby impairing endothelial NO production and Glut-4 translocation in insulin-sensitive tissues, which results in vascular and systemic insulin resistance, respectively. |
| 6627 | 22814999 | On the other hand, Ang II enhances insulin-mediated activation of the mitogen-activated protein kinase (MAPK) pathway, which leads to vasoconstriction and pathologic vascular cellular growth. |
| 6628 | 22814999 | Therefore, the interaction of Ang II with insulin signaling is fully operative not only in insulin-sensitive tissues but also in CV tissues, thereby linking insulin resistance and CV disease. |
| 6629 | 22819562 | In liver, postnatal EO programmed for lower catalase (-42%), superoxide dismutase (-45%) and glutathione peroxidase (-65%) activities. |
| 6630 | 22819562 | Regarding insulin signaling pathway in liver, SL offspring showed lower IRβ (-66%), IRS1 (-50%), phospho-IRS1 (-73%), PI3-K (-30%) and Akt1 (-58%). |
| 6631 | 22872237 | Congenital generalized lipodystrophy (CGL), secondary to AGPAT2 mutation is characterized by the absence of adipocytes and development of severe insulin resistance. |
| 6632 | 22872237 | Lack of AGPAT2 activity reduces Akt activation, and overexpression of constitutively active Akt can partially restore lipogenesis. |
| 6633 | 22872237 | We conclude that AGPAT2 regulates adipogenesis through the modulation of the lipome, altering normal activation of phosphatidylinositol 3-kinase (PI3K)/Akt and PPARγ pathways in the early stages of adipogenesis. |
| 6634 | 22875989 | PTEN, a widely known negative regulator of insulin/PI3K signaling, positively regulates neuronal insulin resistance. |
| 6635 | 22875989 | Lipid and protein tyrosine phosphatase, phosphatase and tension homologue (PTEN), is a widely known negative regulator of insulin/phosphoinositide 3-kinase signaling. |
| 6636 | 22875989 | Down-regulation of PTEN is thus widely documented to ameliorate insulin resistance in peripheral tissues such as skeletal muscle and adipose. |
| 6637 | 22875989 | The present study shows that PTEN, paradoxically, positively regulates neuronal insulin signaling and glucose uptake. |
| 6638 | 22875989 | The positive role of PTEN in neuronal insulin signaling is likely due to its protein phosphatase actions, which prevents the activation of focal adhesion kinase (FAK) and extracellular signal-regulated kinase (ERK), the kinases critically involved in neuronal energy impairment and neurodegeneration. |
| 6639 | 22875989 | Results suggest that PTEN acting through FAK, the direct protein substrate of PTEN, prevents ERK activation. |
| 6640 | 22875989 | Our findings provide an explanation for unexpected outcomes reported earlier with PTEN alterations in neuronal systems and also suggest a novel molecular pathway linking neuronal insulin resistance and AD, the two pathophysiological states demonstrated to be closely linked. |
| 6641 | 22884029 | The unique signaling roles of PI3K pathways instituted by the engagement of the insulin receptor in an autocrine, positive feed-back loop. |
| 6642 | 22914748 | Insulin effects were eliminated in the presence of a ATP-dependent K+ (K(ATP)) channel antagonist tolbutamide (200 μM), or the phosphatidylinositol 3-kinase (PI3K) inhibitor wortmannin (100 nM), suggesting that insulin inhibition of excitatory input to gastric-related DMV neurons was mediated by K(ATP) channels and depended on PI3K activity. |
| 6643 | 22915345 | Retinopathy, a common complication of diabetes, is characterized by an unbalanced production of nitric oxide (NO), a process regulated by nitric oxide synthase (NOS). |
| 6644 | 22915345 | We hypothesized that retinopathy might stem from changes in the insulin receptor substrate (IRS)/PI3K/AKT pathway and/or expression of NOS isoforms. |
| 6645 | 22915345 | Immunoblotting analysis revealed that the retinal tissue of HFD rats had lower levels of AKT(1) , eNOS and nNOS protein than those of samples taken from control animals. |
| 6646 | 22922221 | Tβ4 upregulated angiopoietin-1 (Ang1) expression, but suppressed Ang2 expression in endothelial and Schwann cells in the diabetic sciatic nerve. |
| 6647 | 22922221 | PI3K/Akt signaling pathway is involved in Tβ4-regulated Ang1 expression on endothelial and Schwann cells. |
| 6648 | 22927051 | B. pseudomallei-induced NET formation required NADPH oxidase activation but not phosphatidylinositol-3 kinase, mitogen-activated protein kinases, or Src family kinase signaling pathways. |
| 6649 | 22936542 | Insulin stimulates the proliferation of some human breast cancer cell lines in vitro by mechanisms that use both the phosphatidylinositol-3 kinase and the mitogen-activated protein kinase/Akt signaling pathways; it is also a cell survival (anti-apoptotic) agent and enhances tumor cell migration and invasive capacity. |
| 6650 | 22936542 | In such a system, one adipokine, leptin, has stimulatory paracrine effects on breast cancer cell proliferation and survival, while a second, adiponectin, is inhibitory. |
| 6651 | 22936542 | Leptin, vascular endothelial growth factor, another insulin-regulated adipokine, and insulin itself also stimulate angiogenesis. |
| 6652 | 22936542 | Insulin has complex interactions with estrogens: it induces adipose stromal cell aromatase and tumor cell sex steroid hormone receptor expression and suppresses sex hormone-binding globulin, which may enhance estrogen synthesis and bioactivity with consequent promotion of estrogen-dependent breast cancer. |
| 6653 | 22936933 | Studies employing mice lacking a functional p110δ protein, as well as the use of highly-selective chemical inhibitors of p110δ, have revealed that signaling via p110δ-containing PI3K complexes (PI3Kδ) is critical for B-cell survival, migration, and activation, functioning downstream of key receptors on B cells including the B-cell antigen receptor, chemokine receptors, pro-survival receptors such as BAFF-R and the IL-4 receptor, and co-stimulatory receptors such as CD40 and Toll-like receptors (TLRs). |
| 6654 | 22941040 | We tested expression levels of tumor necrosis factor α (TNFα) mRNA, glucose transporter 4 (GLUT4), peroxisome proliferator-activated receptor γ2 (PPARγ2) and phosphatidylinositol-3-kinase subunit p85α (PI3Kp85α) in the adipose tissues. |
| 6655 | 22941040 | In conclusion, RYGB may improve insulin resistance and treat T2DM through upregulation of the PPARγ2 protein, downregulation of TNFα mRNA transcription, through the autocrine pathway, upregulation of PI3Kp85α expression, upregulation of GLUT4 mRNA transcripts and by inducing translocation of GLUT4 in adipose tissue. |
| 6656 | 22969776 | The insulin receptor substrate 1/phosphatidylinositol 3-kinase association and the activation of protein kinase B were decreased in ERαKO mice, whereas immunostaining for 3-nitrotyrosine was increased. |
| 6657 | 22982565 | Amurensin G enhanced the activities of phosphatidylinositol 3-kinase (PI3K) and Src and their chemical inhibitors suppressed amurensin G-stimulated eNOS phosphorylation. |
| 6658 | 22982565 | Moreover, amurensin G activated AMP-activated protein kinase (AMPK), and amurensin G-stimulated eNOS phosphorylation and PI3K activation were reversed by AMPK inhibition. |
| 6659 | 22982565 | ER inhibition reversed AMPK-dependent PI3K activation in response to amurensin G. |
| 6660 | 22982565 | Amurensin G-mediated endothelium-dependent relaxation was blocked by inhibition of AMPK, ER, Src, or PI3K. |
| 6661 | 22982565 | These results suggest that amurensin G enhances NO production via eNOS phosphorylation in endothelial cells, and ER-dependent AMPK/PI3K pathways are required. |
| 6662 | 22982565 | Amurensin G enhanced the activities of phosphatidylinositol 3-kinase (PI3K) and Src and their chemical inhibitors suppressed amurensin G-stimulated eNOS phosphorylation. |
| 6663 | 22982565 | Moreover, amurensin G activated AMP-activated protein kinase (AMPK), and amurensin G-stimulated eNOS phosphorylation and PI3K activation were reversed by AMPK inhibition. |
| 6664 | 22982565 | ER inhibition reversed AMPK-dependent PI3K activation in response to amurensin G. |
| 6665 | 22982565 | Amurensin G-mediated endothelium-dependent relaxation was blocked by inhibition of AMPK, ER, Src, or PI3K. |
| 6666 | 22982565 | These results suggest that amurensin G enhances NO production via eNOS phosphorylation in endothelial cells, and ER-dependent AMPK/PI3K pathways are required. |
| 6667 | 22982565 | Amurensin G enhanced the activities of phosphatidylinositol 3-kinase (PI3K) and Src and their chemical inhibitors suppressed amurensin G-stimulated eNOS phosphorylation. |
| 6668 | 22982565 | Moreover, amurensin G activated AMP-activated protein kinase (AMPK), and amurensin G-stimulated eNOS phosphorylation and PI3K activation were reversed by AMPK inhibition. |
| 6669 | 22982565 | ER inhibition reversed AMPK-dependent PI3K activation in response to amurensin G. |
| 6670 | 22982565 | Amurensin G-mediated endothelium-dependent relaxation was blocked by inhibition of AMPK, ER, Src, or PI3K. |
| 6671 | 22982565 | These results suggest that amurensin G enhances NO production via eNOS phosphorylation in endothelial cells, and ER-dependent AMPK/PI3K pathways are required. |
| 6672 | 22982565 | Amurensin G enhanced the activities of phosphatidylinositol 3-kinase (PI3K) and Src and their chemical inhibitors suppressed amurensin G-stimulated eNOS phosphorylation. |
| 6673 | 22982565 | Moreover, amurensin G activated AMP-activated protein kinase (AMPK), and amurensin G-stimulated eNOS phosphorylation and PI3K activation were reversed by AMPK inhibition. |
| 6674 | 22982565 | ER inhibition reversed AMPK-dependent PI3K activation in response to amurensin G. |
| 6675 | 22982565 | Amurensin G-mediated endothelium-dependent relaxation was blocked by inhibition of AMPK, ER, Src, or PI3K. |
| 6676 | 22982565 | These results suggest that amurensin G enhances NO production via eNOS phosphorylation in endothelial cells, and ER-dependent AMPK/PI3K pathways are required. |
| 6677 | 22982565 | Amurensin G enhanced the activities of phosphatidylinositol 3-kinase (PI3K) and Src and their chemical inhibitors suppressed amurensin G-stimulated eNOS phosphorylation. |
| 6678 | 22982565 | Moreover, amurensin G activated AMP-activated protein kinase (AMPK), and amurensin G-stimulated eNOS phosphorylation and PI3K activation were reversed by AMPK inhibition. |
| 6679 | 22982565 | ER inhibition reversed AMPK-dependent PI3K activation in response to amurensin G. |
| 6680 | 22982565 | Amurensin G-mediated endothelium-dependent relaxation was blocked by inhibition of AMPK, ER, Src, or PI3K. |
| 6681 | 22982565 | These results suggest that amurensin G enhances NO production via eNOS phosphorylation in endothelial cells, and ER-dependent AMPK/PI3K pathways are required. |
| 6682 | 23012321 | SGK1 is activated by insulin and growth factors through PI3K and 3-phosphoinositide-dependent kinase PDK1. |
| 6683 | 23012321 | SGK1 activates a wide variety of ion channels (e.g., ENaC, SCN5A, TRPV4-6, ROMK, Kv1.3, Kv1.5, Kv4.3, KCNE1/KCNQ1, KCNQ4, ASIC1, GluR6, ClCKa/barttin, ClC2, CFTR, and Orai/STIM), which participate in the regulation of transport, hormone release, neuroexcitability, inflammation, cell proliferation, and apoptosis. |
| 6684 | 23018458 | Insulin modulates the inflammatory granulocyte response to streptococci via phosphatidylinositol 3-kinase. |
| 6685 | 23018458 | We found that GBS-induced, MyD88-dependent chemokine formation of PML was specifically downmodulated by insulin via insulin receptor-mediated induction of PI3K. |
| 6686 | 23018458 | The targeted modulation of bacteria-induced chemokine formation by insulin via PI3K may form a basis for the development of novel targets of adjunctive sepsis therapy. |
| 6687 | 23018458 | Insulin modulates the inflammatory granulocyte response to streptococci via phosphatidylinositol 3-kinase. |
| 6688 | 23018458 | We found that GBS-induced, MyD88-dependent chemokine formation of PML was specifically downmodulated by insulin via insulin receptor-mediated induction of PI3K. |
| 6689 | 23018458 | The targeted modulation of bacteria-induced chemokine formation by insulin via PI3K may form a basis for the development of novel targets of adjunctive sepsis therapy. |
| 6690 | 23018458 | Insulin modulates the inflammatory granulocyte response to streptococci via phosphatidylinositol 3-kinase. |
| 6691 | 23018458 | We found that GBS-induced, MyD88-dependent chemokine formation of PML was specifically downmodulated by insulin via insulin receptor-mediated induction of PI3K. |
| 6692 | 23018458 | The targeted modulation of bacteria-induced chemokine formation by insulin via PI3K may form a basis for the development of novel targets of adjunctive sepsis therapy. |
| 6693 | 23041393 | Kidney proximal tubular epithelial-specific overexpression of netrin-1 suppresses inflammation and albuminuria through suppression of COX-2-mediated PGE2 production in streptozotocin-induced diabetic mice. |
| 6694 | 23041393 | Netrin-1-induced suppression of PGE2 production was mediated through suppression of NFκB-mediated cyclooxygenase-2 (COX-2) in renal tubular epithelial cells. |
| 6695 | 23041393 | Furthermore, netrin-1 also increased albumin uptake by proximal tubular epithelial cells through the PI3K and ERK pathways without increasing glucose uptake. |
| 6696 | 23059845 | Seven days post-injection, Wt diabetic animals showed a decrease in PI3K activity and P-Akt levels, an increase of P-JNK, P-p38, pro-apoptotic Bad and Bax, release of cytochrome c and activities of caspases-3 and -9, leading to an increased apoptotic index. |
| 6697 | 23059845 | In addition, SID COX-2 Tg showed increased expression of anti-apoptotic Mcl-1 and XIAP. |
| 6698 | 23085267 | The AMP-activated protein kinase (AMPK) is a ubiquitously expressed serine/threonine protein kinase that functions as an intracellular fuel sensor. |
| 6699 | 23085267 | In vitro studies further show that GY3 improved glucose and lipid metabolism through an AMPK-dependent pathway but not the PI3K pathway. |
| 6700 | 23086038 | Phosphoinositide 3-kinase (PI3K) mediates insulin actions by relaying signals from insulin receptors (IRs) to downstream targets. |
| 6701 | 23086038 | The p110α catalytic subunit of class IA PI3K is the primary insulin-responsive PI3K implicated in insulin signaling. |
| 6702 | 23086038 | We demonstrate here a new mode of spatial regulation for the p110α subunit of PI3K by PAQR3 that is exclusively localized in the Golgi apparatus. |
| 6703 | 23086038 | Insulin-stimulated PI3K activity and phosphoinositide (3,4,5)-triphosphate production are enhanced by Paqr3 deletion and reduced by PAQR3 overexpression in hepatocytes. |
| 6704 | 23086038 | Deletion of Paqr3 enhances insulin-stimulated phosphorylation of AKT and glycogen synthase kinase 3β, but not phosphorylation of IR and IR substrate-1 (IRS-1), in hepatocytes, mouse liver, and skeletal muscle. |
| 6705 | 23086038 | Insulin-stimulated GLUT4 translocation to the plasma membrane and glucose uptake are enhanced by Paqr3 ablation. |
| 6706 | 23086038 | Furthermore, PAQR3 interacts with the domain of p110α involved in its binding with p85, the regulatory subunit of PI3K. |
| 6707 | 23086038 | Thus, PAQR3 negatively regulates insulin signaling by shunting cytosolic p110α to the Golgi apparatus while competing with p85 subunit in forming a PI3K complex with p110α. |
| 6708 | 23086038 | Phosphoinositide 3-kinase (PI3K) mediates insulin actions by relaying signals from insulin receptors (IRs) to downstream targets. |
| 6709 | 23086038 | The p110α catalytic subunit of class IA PI3K is the primary insulin-responsive PI3K implicated in insulin signaling. |
| 6710 | 23086038 | We demonstrate here a new mode of spatial regulation for the p110α subunit of PI3K by PAQR3 that is exclusively localized in the Golgi apparatus. |
| 6711 | 23086038 | Insulin-stimulated PI3K activity and phosphoinositide (3,4,5)-triphosphate production are enhanced by Paqr3 deletion and reduced by PAQR3 overexpression in hepatocytes. |
| 6712 | 23086038 | Deletion of Paqr3 enhances insulin-stimulated phosphorylation of AKT and glycogen synthase kinase 3β, but not phosphorylation of IR and IR substrate-1 (IRS-1), in hepatocytes, mouse liver, and skeletal muscle. |
| 6713 | 23086038 | Insulin-stimulated GLUT4 translocation to the plasma membrane and glucose uptake are enhanced by Paqr3 ablation. |
| 6714 | 23086038 | Furthermore, PAQR3 interacts with the domain of p110α involved in its binding with p85, the regulatory subunit of PI3K. |
| 6715 | 23086038 | Thus, PAQR3 negatively regulates insulin signaling by shunting cytosolic p110α to the Golgi apparatus while competing with p85 subunit in forming a PI3K complex with p110α. |
| 6716 | 23086038 | Phosphoinositide 3-kinase (PI3K) mediates insulin actions by relaying signals from insulin receptors (IRs) to downstream targets. |
| 6717 | 23086038 | The p110α catalytic subunit of class IA PI3K is the primary insulin-responsive PI3K implicated in insulin signaling. |
| 6718 | 23086038 | We demonstrate here a new mode of spatial regulation for the p110α subunit of PI3K by PAQR3 that is exclusively localized in the Golgi apparatus. |
| 6719 | 23086038 | Insulin-stimulated PI3K activity and phosphoinositide (3,4,5)-triphosphate production are enhanced by Paqr3 deletion and reduced by PAQR3 overexpression in hepatocytes. |
| 6720 | 23086038 | Deletion of Paqr3 enhances insulin-stimulated phosphorylation of AKT and glycogen synthase kinase 3β, but not phosphorylation of IR and IR substrate-1 (IRS-1), in hepatocytes, mouse liver, and skeletal muscle. |
| 6721 | 23086038 | Insulin-stimulated GLUT4 translocation to the plasma membrane and glucose uptake are enhanced by Paqr3 ablation. |
| 6722 | 23086038 | Furthermore, PAQR3 interacts with the domain of p110α involved in its binding with p85, the regulatory subunit of PI3K. |
| 6723 | 23086038 | Thus, PAQR3 negatively regulates insulin signaling by shunting cytosolic p110α to the Golgi apparatus while competing with p85 subunit in forming a PI3K complex with p110α. |
| 6724 | 23086038 | Phosphoinositide 3-kinase (PI3K) mediates insulin actions by relaying signals from insulin receptors (IRs) to downstream targets. |
| 6725 | 23086038 | The p110α catalytic subunit of class IA PI3K is the primary insulin-responsive PI3K implicated in insulin signaling. |
| 6726 | 23086038 | We demonstrate here a new mode of spatial regulation for the p110α subunit of PI3K by PAQR3 that is exclusively localized in the Golgi apparatus. |
| 6727 | 23086038 | Insulin-stimulated PI3K activity and phosphoinositide (3,4,5)-triphosphate production are enhanced by Paqr3 deletion and reduced by PAQR3 overexpression in hepatocytes. |
| 6728 | 23086038 | Deletion of Paqr3 enhances insulin-stimulated phosphorylation of AKT and glycogen synthase kinase 3β, but not phosphorylation of IR and IR substrate-1 (IRS-1), in hepatocytes, mouse liver, and skeletal muscle. |
| 6729 | 23086038 | Insulin-stimulated GLUT4 translocation to the plasma membrane and glucose uptake are enhanced by Paqr3 ablation. |
| 6730 | 23086038 | Furthermore, PAQR3 interacts with the domain of p110α involved in its binding with p85, the regulatory subunit of PI3K. |
| 6731 | 23086038 | Thus, PAQR3 negatively regulates insulin signaling by shunting cytosolic p110α to the Golgi apparatus while competing with p85 subunit in forming a PI3K complex with p110α. |
| 6732 | 23086038 | Phosphoinositide 3-kinase (PI3K) mediates insulin actions by relaying signals from insulin receptors (IRs) to downstream targets. |
| 6733 | 23086038 | The p110α catalytic subunit of class IA PI3K is the primary insulin-responsive PI3K implicated in insulin signaling. |
| 6734 | 23086038 | We demonstrate here a new mode of spatial regulation for the p110α subunit of PI3K by PAQR3 that is exclusively localized in the Golgi apparatus. |
| 6735 | 23086038 | Insulin-stimulated PI3K activity and phosphoinositide (3,4,5)-triphosphate production are enhanced by Paqr3 deletion and reduced by PAQR3 overexpression in hepatocytes. |
| 6736 | 23086038 | Deletion of Paqr3 enhances insulin-stimulated phosphorylation of AKT and glycogen synthase kinase 3β, but not phosphorylation of IR and IR substrate-1 (IRS-1), in hepatocytes, mouse liver, and skeletal muscle. |
| 6737 | 23086038 | Insulin-stimulated GLUT4 translocation to the plasma membrane and glucose uptake are enhanced by Paqr3 ablation. |
| 6738 | 23086038 | Furthermore, PAQR3 interacts with the domain of p110α involved in its binding with p85, the regulatory subunit of PI3K. |
| 6739 | 23086038 | Thus, PAQR3 negatively regulates insulin signaling by shunting cytosolic p110α to the Golgi apparatus while competing with p85 subunit in forming a PI3K complex with p110α. |
| 6740 | 23086038 | Phosphoinositide 3-kinase (PI3K) mediates insulin actions by relaying signals from insulin receptors (IRs) to downstream targets. |
| 6741 | 23086038 | The p110α catalytic subunit of class IA PI3K is the primary insulin-responsive PI3K implicated in insulin signaling. |
| 6742 | 23086038 | We demonstrate here a new mode of spatial regulation for the p110α subunit of PI3K by PAQR3 that is exclusively localized in the Golgi apparatus. |
| 6743 | 23086038 | Insulin-stimulated PI3K activity and phosphoinositide (3,4,5)-triphosphate production are enhanced by Paqr3 deletion and reduced by PAQR3 overexpression in hepatocytes. |
| 6744 | 23086038 | Deletion of Paqr3 enhances insulin-stimulated phosphorylation of AKT and glycogen synthase kinase 3β, but not phosphorylation of IR and IR substrate-1 (IRS-1), in hepatocytes, mouse liver, and skeletal muscle. |
| 6745 | 23086038 | Insulin-stimulated GLUT4 translocation to the plasma membrane and glucose uptake are enhanced by Paqr3 ablation. |
| 6746 | 23086038 | Furthermore, PAQR3 interacts with the domain of p110α involved in its binding with p85, the regulatory subunit of PI3K. |
| 6747 | 23086038 | Thus, PAQR3 negatively regulates insulin signaling by shunting cytosolic p110α to the Golgi apparatus while competing with p85 subunit in forming a PI3K complex with p110α. |
| 6748 | 23086422 | The phosphoinositide phosphatases regulate PI3K/Akt signalling, insulin signalling, endocytosis, vesicle trafficking, cell migration, proliferation and apoptosis. |
| 6749 | 23086422 | Genetic mutations in the 5-phosphatase INPP5E are causative of the ciliopathy syndromes Joubert and MORM, and mutations in the 5-phosphatase OCRL result in Lowe's syndrome and Dent 2 disease. |
| 6750 | 23086422 | Additionally, polymorphisms in the 5-phosphatase SHIP2 confer diabetes susceptibility in specific populations, whereas reduced protein expression of SHIP1 is reported in several human leukaemias. |
| 6751 | 23086422 | Mutations in one SAC phosphatase, SAC3/FIG4, results in the degenerative neuropathy, Charcot-Marie-Tooth disease. |
| 6752 | 23104384 | Insulin sensitization via partial agonism of PPARγ and glucose uptake through translocation and activation of GLUT4 in PI3K/p-Akt signaling pathway by embelin in type 2 diabetic rats. |
| 6753 | 23130316 | Transcriptional regulation of pyruvate dehydrogenase kinase. |
| 6754 | 23130316 | The pyruvate dehydrogenase complex (PDC) activity is crucial to maintains blood glucose and ATP levels, which largely depends on the phosphorylation status by pyruvate dehydrogenase kinase (PDK) isoenzymes. |
| 6755 | 23130316 | Although it has been reported that PDC is phosphorylated and inactivated by PDK2 and PDK4 in metabolically active tissues including liver, skeletal muscle, heart, and kidney during starvation and diabetes, the precise mechanisms by which expression of PDK2 and PDK4 are transcriptionally regulated still remains unclear. |
| 6756 | 23130316 | Insulin represses the expression of PDK2 and PDK4 via phosphorylation of FOXO through PI3K/Akt signaling pathway. |
| 6757 | 23130316 | Several nuclear hormone receptors activated due to fasting or increased fat supply, including peroxisome proliferator-activated receptors, glucocorticoid receptors, estrogen-related receptors, and thyroid hormone receptors, also participate in the up-regulation of PDK2 and PDK4; however, the endogenous ligands that bind those nuclear receptors have not been identified. |
| 6758 | 23130316 | It has been recently suggested that growth hormone, adiponectin, epinephrine, and rosiglitazone also control the expression of PDK4 in tissue-specific manners. |
| 6759 | 23130316 | In this review, we discuss several factors involved in the expressional regulation of PDK2 and PDK4, and introduce current studies aimed at providing a better understanding of the molecular mechanisms that underlie the development of metabolic diseases such as diabetes. |
| 6760 | 23142567 | c-Jun NH2-terminal kinases (JNKs) and phosphatidylinositol 3-kinase (PI3-K) play critical roles in chronic diseases such as cancer, type II diabetes, and obesity. |
| 6761 | 23142567 | We describe here the binding of quercetagetin (3,3',4',5,6,7-hydroxyflavone), related flavonoids, and SP600125 to JNK1 and PI3-K by ATP-competitive and immobilized metal ion affinity-based fluorescence polarization assays and measure the effect of quercetagetin on JNK1 and PI3-K activities. |
| 6762 | 23142567 | Quercetagetin attenuated the phosphorylation of c-Jun and AKT, suppressed AP-1 and NF-κB promoter activities, and also reduced cell transformation. |
| 6763 | 23142567 | c-Jun NH2-terminal kinases (JNKs) and phosphatidylinositol 3-kinase (PI3-K) play critical roles in chronic diseases such as cancer, type II diabetes, and obesity. |
| 6764 | 23142567 | We describe here the binding of quercetagetin (3,3',4',5,6,7-hydroxyflavone), related flavonoids, and SP600125 to JNK1 and PI3-K by ATP-competitive and immobilized metal ion affinity-based fluorescence polarization assays and measure the effect of quercetagetin on JNK1 and PI3-K activities. |
| 6765 | 23142567 | Quercetagetin attenuated the phosphorylation of c-Jun and AKT, suppressed AP-1 and NF-κB promoter activities, and also reduced cell transformation. |
| 6766 | 23147208 | Triiodothyronine (T3) induces proinsulin gene expression by activating PI3K: possible roles for GSK-3β and the transcriptional factor PDX-1. |
| 6767 | 23147208 | Thyroid hormone (TH) activates PI3K and Akt, leading to glucose uptake in rat skeletal muscle cells and proliferation of insulinoma cells, respectively. |
| 6768 | 23147208 | However, TH actions on pancreatic beta cells have been little explored, which lead us to evaluate the TH eff ects on proinsulin gene expression, and the involvement of PI3K/Akt/GSK-3β signaling pathway, and a transcriptional factor for insulin (PDX-1). |
| 6769 | 23147208 | Proinsulin mRNA expression was evaluated by real time PCR, and pGSK-3β and PDX-1 protein content was analyzed by Western blotting. |
| 6770 | 23147208 | ActD, CHX and wortmannin, but not Akt inhibitor, prevented the rapid stimulatory eff ect of T3 on proinsulin mRNA expression. |
| 6771 | 23147208 | These data indicate that T3 acutely increases proinsulin mRNA expression, by mechanisms which depends on the activation of PI3K, but not of Akt, and may involve the inactivation of GSK-3β by phosphorylation. |
| 6772 | 23147208 | Considering that PDX-1 is one of the most important transcriptional factors for proinsulin gene expression, its enhancement may underlie the increased proinsulin mRNA content acutely induced by T3. |
| 6773 | 23147208 | Triiodothyronine (T3) induces proinsulin gene expression by activating PI3K: possible roles for GSK-3β and the transcriptional factor PDX-1. |
| 6774 | 23147208 | Thyroid hormone (TH) activates PI3K and Akt, leading to glucose uptake in rat skeletal muscle cells and proliferation of insulinoma cells, respectively. |
| 6775 | 23147208 | However, TH actions on pancreatic beta cells have been little explored, which lead us to evaluate the TH eff ects on proinsulin gene expression, and the involvement of PI3K/Akt/GSK-3β signaling pathway, and a transcriptional factor for insulin (PDX-1). |
| 6776 | 23147208 | Proinsulin mRNA expression was evaluated by real time PCR, and pGSK-3β and PDX-1 protein content was analyzed by Western blotting. |
| 6777 | 23147208 | ActD, CHX and wortmannin, but not Akt inhibitor, prevented the rapid stimulatory eff ect of T3 on proinsulin mRNA expression. |
| 6778 | 23147208 | These data indicate that T3 acutely increases proinsulin mRNA expression, by mechanisms which depends on the activation of PI3K, but not of Akt, and may involve the inactivation of GSK-3β by phosphorylation. |
| 6779 | 23147208 | Considering that PDX-1 is one of the most important transcriptional factors for proinsulin gene expression, its enhancement may underlie the increased proinsulin mRNA content acutely induced by T3. |
| 6780 | 23147208 | Triiodothyronine (T3) induces proinsulin gene expression by activating PI3K: possible roles for GSK-3β and the transcriptional factor PDX-1. |
| 6781 | 23147208 | Thyroid hormone (TH) activates PI3K and Akt, leading to glucose uptake in rat skeletal muscle cells and proliferation of insulinoma cells, respectively. |
| 6782 | 23147208 | However, TH actions on pancreatic beta cells have been little explored, which lead us to evaluate the TH eff ects on proinsulin gene expression, and the involvement of PI3K/Akt/GSK-3β signaling pathway, and a transcriptional factor for insulin (PDX-1). |
| 6783 | 23147208 | Proinsulin mRNA expression was evaluated by real time PCR, and pGSK-3β and PDX-1 protein content was analyzed by Western blotting. |
| 6784 | 23147208 | ActD, CHX and wortmannin, but not Akt inhibitor, prevented the rapid stimulatory eff ect of T3 on proinsulin mRNA expression. |
| 6785 | 23147208 | These data indicate that T3 acutely increases proinsulin mRNA expression, by mechanisms which depends on the activation of PI3K, but not of Akt, and may involve the inactivation of GSK-3β by phosphorylation. |
| 6786 | 23147208 | Considering that PDX-1 is one of the most important transcriptional factors for proinsulin gene expression, its enhancement may underlie the increased proinsulin mRNA content acutely induced by T3. |
| 6787 | 23147208 | Triiodothyronine (T3) induces proinsulin gene expression by activating PI3K: possible roles for GSK-3β and the transcriptional factor PDX-1. |
| 6788 | 23147208 | Thyroid hormone (TH) activates PI3K and Akt, leading to glucose uptake in rat skeletal muscle cells and proliferation of insulinoma cells, respectively. |
| 6789 | 23147208 | However, TH actions on pancreatic beta cells have been little explored, which lead us to evaluate the TH eff ects on proinsulin gene expression, and the involvement of PI3K/Akt/GSK-3β signaling pathway, and a transcriptional factor for insulin (PDX-1). |
| 6790 | 23147208 | Proinsulin mRNA expression was evaluated by real time PCR, and pGSK-3β and PDX-1 protein content was analyzed by Western blotting. |
| 6791 | 23147208 | ActD, CHX and wortmannin, but not Akt inhibitor, prevented the rapid stimulatory eff ect of T3 on proinsulin mRNA expression. |
| 6792 | 23147208 | These data indicate that T3 acutely increases proinsulin mRNA expression, by mechanisms which depends on the activation of PI3K, but not of Akt, and may involve the inactivation of GSK-3β by phosphorylation. |
| 6793 | 23147208 | Considering that PDX-1 is one of the most important transcriptional factors for proinsulin gene expression, its enhancement may underlie the increased proinsulin mRNA content acutely induced by T3. |
| 6794 | 23230080 | Activation of the ACE2/angiotensin-(1-7)/Mas receptor axis enhances the reparative function of dysfunctional diabetic endothelial progenitors. |
| 6795 | 23230080 | We tested the hypothesis that activation of the protective arm of the renin angiotensin system, the angiotensin-converting enzyme 2 (ACE2)/angiotensin-(1-7) [Ang-(1-7)]/Mas receptor axis, corrects the vasoreparative dysfunction typically seen in the CD34(+) cells isolated from diabetic individuals. |
| 6796 | 23230080 | The survival and proliferation of CD34(+) cells from diabetic individuals were enhanced by Ang-(1-7) in a Mas/phosphatidylinositol 3-kinase (PI3K)/Akt-dependent manner. |
| 6797 | 23230080 | A cohort of patients who remained free of microvascular complications despite having a history of longstanding inadequate glycemic control had higher expression of ACE2/Mas mRNA than patients with diabetes with microvascular complications matched for age, sex, and glycemic control. |
| 6798 | 23230080 | Thus, ACE2/Ang-(1-7)Mas pathway activation corrects existing diabetes-induced CD34(+) cell dysfunction and also confers protection from development of this dysfunction. |
| 6799 | 23238567 | Sestrin2 integrates Akt and mTOR signaling to protect cells against energetic stress-induced death. |
| 6800 | 23238567 | The phosphoinositide-3 kinase/Akt (PI3K/Akt) pathway has a central role in cancer cell metabolism and proliferation. |
| 6801 | 23238567 | Here, we show that Sestrin2 (Sesn2), also known as Hi95, a p53 target gene that protects cells against oxidative and genotoxic stresses, participates in the protective role of Akt in response to an energetic stress induced by 2-deoxyglucose (2-DG). |
| 6802 | 23238567 | The increase of Sesn2 is independent of p53 but requires the anti-apoptotic pathway, PI3K/Akt. |
| 6803 | 23238567 | Sestrin2 integrates Akt and mTOR signaling to protect cells against energetic stress-induced death. |
| 6804 | 23238567 | The phosphoinositide-3 kinase/Akt (PI3K/Akt) pathway has a central role in cancer cell metabolism and proliferation. |
| 6805 | 23238567 | Here, we show that Sestrin2 (Sesn2), also known as Hi95, a p53 target gene that protects cells against oxidative and genotoxic stresses, participates in the protective role of Akt in response to an energetic stress induced by 2-deoxyglucose (2-DG). |
| 6806 | 23238567 | The increase of Sesn2 is independent of p53 but requires the anti-apoptotic pathway, PI3K/Akt. |
| 6807 | 23266931 | The molecular mechanism responsible for the insulin-like effects of Zn compounds involves the activation of several key components of the insulin signaling pathways, which include the extracellular signal-regulated kinase 1/2 (ERK1/2) and phosphatidylinositol 3-kinase (PI3-K)/protein kinase B/Akt (PKB/Akt) pathways. |
| 6808 | 23272147 | Effects of exercise on AMPK signaling and downstream components to PI3K in rat with type 2 diabetes. |
| 6809 | 23272147 | We also investigated the possible mechanism by which chronic and acute exercise improves metabolism, and the phosphorylation and expression of components of AMP-activated protein kinase (AMPK) and downstream components of phosphatidylinositol 3-kinase (PI3K) signaling pathways in the soleus. |
| 6810 | 23272147 | Interestingly, chronic and acute exercise reduced blood glucose, increased phosphorylation and expression of AMPKα1/2 and the isoforms AMPKα1 and AMPKα2, and decreased phosphorylation and expression of AMPK substrate, acetyl CoA carboxylase (ACC). |
| 6811 | 23272147 | Chronic exercise upregulated phosphorylation and expression of AMPK upstream kinase, LKB1. |
| 6812 | 23272147 | Additionally, exercise also increased protein kinase B (PKB)/Akt1, Akt2 and GLUT4 expression, but AS160 protein expression was unchanged. |
| 6813 | 23272147 | Chronic exercise elevated Akt (Thr(308)) and (Ser(473)) and AS160 phosphorylation. |
| 6814 | 23272147 | These results indicate that both chronic and acute exercise influence the phosphorylation and expression of components of the AMPK and downstream to PIK3 (aPKC, Akt), and improve GLUT4 trafficking in skeletal muscle. |
| 6815 | 23272147 | Effects of exercise on AMPK signaling and downstream components to PI3K in rat with type 2 diabetes. |
| 6816 | 23272147 | We also investigated the possible mechanism by which chronic and acute exercise improves metabolism, and the phosphorylation and expression of components of AMP-activated protein kinase (AMPK) and downstream components of phosphatidylinositol 3-kinase (PI3K) signaling pathways in the soleus. |
| 6817 | 23272147 | Interestingly, chronic and acute exercise reduced blood glucose, increased phosphorylation and expression of AMPKα1/2 and the isoforms AMPKα1 and AMPKα2, and decreased phosphorylation and expression of AMPK substrate, acetyl CoA carboxylase (ACC). |
| 6818 | 23272147 | Chronic exercise upregulated phosphorylation and expression of AMPK upstream kinase, LKB1. |
| 6819 | 23272147 | Additionally, exercise also increased protein kinase B (PKB)/Akt1, Akt2 and GLUT4 expression, but AS160 protein expression was unchanged. |
| 6820 | 23272147 | Chronic exercise elevated Akt (Thr(308)) and (Ser(473)) and AS160 phosphorylation. |
| 6821 | 23272147 | These results indicate that both chronic and acute exercise influence the phosphorylation and expression of components of the AMPK and downstream to PIK3 (aPKC, Akt), and improve GLUT4 trafficking in skeletal muscle. |
| 6822 | 23285235 | In the rat retina immunoprecipitation and Western blot analysis revealed a protein with an apparent molecular mass of 45 kDa. ¹⁴C-glucose accumulation by isolated rat retinas was significantly enhanced by physiological concentrations of insulin, an effect blocked by inhibitors of phosphatidyl-inositol 3-kinase (PI3K), a key enzyme in the insulin-signaling pathway in other tissues. |
| 6823 | 23285235 | Besides, insulin induced phosphorylation of Akt, an effect also blocked by PI3K inhibition. |
| 6824 | 23285235 | To our knowledge, our results provide the first evidence of Glut4 expression in the retina, suggesting it as an insulin- responsive tissue. |
| 6825 | 23285235 | In the rat retina immunoprecipitation and Western blot analysis revealed a protein with an apparent molecular mass of 45 kDa. ¹⁴C-glucose accumulation by isolated rat retinas was significantly enhanced by physiological concentrations of insulin, an effect blocked by inhibitors of phosphatidyl-inositol 3-kinase (PI3K), a key enzyme in the insulin-signaling pathway in other tissues. |
| 6826 | 23285235 | Besides, insulin induced phosphorylation of Akt, an effect also blocked by PI3K inhibition. |
| 6827 | 23285235 | To our knowledge, our results provide the first evidence of Glut4 expression in the retina, suggesting it as an insulin- responsive tissue. |
| 6828 | 23306778 | The balance between nitric oxide (NO)-dependent vasodilator actions and endothelin-1- dependent vasoconstrictor actions of insulin is regulated by phosphatidylinositol 3-kinase-dependent (PI3K) - and mitogen-activated protein kinase (MAPK)-dependent signaling in vascular endothelium, respectively. |
| 6829 | 23306778 | During insulin-resistant conditions, pathway-specific impairment in PI3K-dependent signaling may cause imbalance between production of NO and secretion of endothelin-1 and lead to endothelial dysfunction. |
| 6830 | 23306778 | The balance between nitric oxide (NO)-dependent vasodilator actions and endothelin-1- dependent vasoconstrictor actions of insulin is regulated by phosphatidylinositol 3-kinase-dependent (PI3K) - and mitogen-activated protein kinase (MAPK)-dependent signaling in vascular endothelium, respectively. |
| 6831 | 23306778 | During insulin-resistant conditions, pathway-specific impairment in PI3K-dependent signaling may cause imbalance between production of NO and secretion of endothelin-1 and lead to endothelial dysfunction. |
| 6832 | 23326455 | The levels of fasting blood glucose, serum insulin and glucose tolerance were measured and the relative levels of insulin-related phosphatidylinositol 3-kinase (PI3K)/Akt, insulin receptor (IR) and IR substrate 1 (IRS1) phosphorylation were determined. |
| 6833 | 23326455 | The levels of phosphoenolpyruvate carboxykinase (PEPCK), glucose-6- phosphatase (G6Pase), toll like receptor 4 (TLR4), tumor necrosis factor (TNF)-α and IL-6 expression and nuclear factor-κB (NF-κB) and c-Jun N-terminal kinase (JNK), extracellular-signal-regulated kinase (ERK) and p38 MAPK activation in the liver were examined. |
| 6834 | 23326455 | EPO treatment significantly reduced the body weights and the levels of fasting blood glucose and serum insulin and improved the HFD-induced glucose intolerance in mice. |
| 6835 | 23326455 | EPO treatment significantly enhanced the levels of Akt, but not IR and IRS1, phosphorylation, accompanied by inhibiting the PEPCK and G6Pase expression in the liver. |
| 6836 | 23326455 | Furthermore, EPO treatment mitigated the HFD-induced inflammatory TNF-α and IL-6 production, TLR4 expression, NF-κB and JNK, but not ERK and p38 MAPK, phosphorylation in the liver. |
| 6837 | 23326534 | The results show that H(2) promoted 2-[(14)C]-deoxy-d-glucose (2-DG) uptake into C2C12 cells via the translocation of glucose transporter Glut4 through activation of phosphatidylinositol-3-OH kinase (PI3K), protein kinase C (PKC), and AMP-activated protein kinase (AMPK), although it did not stimulate the translocation of Glut2 in Hep G2 cells. |
| 6838 | 23404499 | In investigating the associated mechanisms, we found that leucine itself does not activate the classical Akt- or ERK1/2 MAP kinase-dependent signaling pathways but can facilitate the insulin-induced phosphorylations of Akt(473) and ERK1/2 in a time- and dose-dependent manner in cultured hepatocytes. |
| 6839 | 23404499 | The leucine-facilitated insulin-induced phosphorylation of Akt at residue 473 was not affected by knocking down the key component of mTORC1 or -2 complexes but was blocked by inhibition of c-Src (PP2), PI3K (LY294002), Gαi protein (pertussis toxin or siRNA against Gαi1 gene, or β-arrestin 2 (siRNA)). |
| 6840 | 23404499 | Similarly, the leucine-facilitated insulin activation of ERK1/2 was also blunted by pertussis toxin. |
| 6841 | 23428406 | Inhibitors analyses revealed that F015-induced glucose uptake was dependent on the activation of phosphatidylinositol-3-kinase (PI-3-K) and extracellular signal-regulated kinases 1 and 2 (ERK1/2), while independent to the activation of 5'AMP-activated kinase (AMPK). |
| 6842 | 23428406 | F015 significantly increased the phosphorylation of AKT, AS160 and ERK1/2, account for the augmented glucose transport capacity in L6 myotubes. |
| 6843 | 23431468 | Roles for PI3K/AKT/PTEN Pathway in Cell Signaling of Nonalcoholic Fatty Liver Disease. |
| 6844 | 23431468 | However, accumulating evidence indicates that deregulation of the phosphatidylinositol 3-kinase (PI3K)/AKT pathway in hepatocytes is a common molecular event associated with metabolic dysfunctions including obesity, metabolic syndrome, and the NAFLD. |
| 6845 | 23431468 | A tumor suppressor PTEN negatively regulates the PI3K/AKT pathways through its lipid phosphatase activity. |
| 6846 | 23431468 | Molecular studies in the NAFLD support a key role for PTEN in hepatic insulin sensitivity and the development of steatosis, steatohepatitis, and fibrosis. |
| 6847 | 23431468 | We review recent studies on the features of the PTEN and the PI3K/AKT pathway and discuss the protein functions in the signaling pathways involved in the NAFLD. |
| 6848 | 23431468 | Roles for PI3K/AKT/PTEN Pathway in Cell Signaling of Nonalcoholic Fatty Liver Disease. |
| 6849 | 23431468 | However, accumulating evidence indicates that deregulation of the phosphatidylinositol 3-kinase (PI3K)/AKT pathway in hepatocytes is a common molecular event associated with metabolic dysfunctions including obesity, metabolic syndrome, and the NAFLD. |
| 6850 | 23431468 | A tumor suppressor PTEN negatively regulates the PI3K/AKT pathways through its lipid phosphatase activity. |
| 6851 | 23431468 | Molecular studies in the NAFLD support a key role for PTEN in hepatic insulin sensitivity and the development of steatosis, steatohepatitis, and fibrosis. |
| 6852 | 23431468 | We review recent studies on the features of the PTEN and the PI3K/AKT pathway and discuss the protein functions in the signaling pathways involved in the NAFLD. |
| 6853 | 23431468 | Roles for PI3K/AKT/PTEN Pathway in Cell Signaling of Nonalcoholic Fatty Liver Disease. |
| 6854 | 23431468 | However, accumulating evidence indicates that deregulation of the phosphatidylinositol 3-kinase (PI3K)/AKT pathway in hepatocytes is a common molecular event associated with metabolic dysfunctions including obesity, metabolic syndrome, and the NAFLD. |
| 6855 | 23431468 | A tumor suppressor PTEN negatively regulates the PI3K/AKT pathways through its lipid phosphatase activity. |
| 6856 | 23431468 | Molecular studies in the NAFLD support a key role for PTEN in hepatic insulin sensitivity and the development of steatosis, steatohepatitis, and fibrosis. |
| 6857 | 23431468 | We review recent studies on the features of the PTEN and the PI3K/AKT pathway and discuss the protein functions in the signaling pathways involved in the NAFLD. |
| 6858 | 23431468 | Roles for PI3K/AKT/PTEN Pathway in Cell Signaling of Nonalcoholic Fatty Liver Disease. |
| 6859 | 23431468 | However, accumulating evidence indicates that deregulation of the phosphatidylinositol 3-kinase (PI3K)/AKT pathway in hepatocytes is a common molecular event associated with metabolic dysfunctions including obesity, metabolic syndrome, and the NAFLD. |
| 6860 | 23431468 | A tumor suppressor PTEN negatively regulates the PI3K/AKT pathways through its lipid phosphatase activity. |
| 6861 | 23431468 | Molecular studies in the NAFLD support a key role for PTEN in hepatic insulin sensitivity and the development of steatosis, steatohepatitis, and fibrosis. |
| 6862 | 23431468 | We review recent studies on the features of the PTEN and the PI3K/AKT pathway and discuss the protein functions in the signaling pathways involved in the NAFLD. |
| 6863 | 23437325 | Impaired insulin signaling is a key feature of type 2 diabetes and is associated with increased ubiquitin-proteasome-dependent protein degradation in skeletal muscle. |
| 6864 | 23437325 | We sought to determine if the effect of PMI5011 on insulin signaling extends to regulation of the ubiquitin-proteasome system. |
| 6865 | 23437325 | C2C12 myotubes and the KK-A(y) murine model of type 2 diabetes were used to evaluate the effect of PMI5011 on steady-state levels of ubiquitylation, proteasome activity and expression of Atrogin-1 and MuRF-1, muscle-specific ubiquitin ligases that are upregulated with impaired insulin signaling. |
| 6866 | 23437325 | The effect of PMI5011 is mediated by PI3K/Akt signaling and correlates with decreased expression of Atrogin-1 and MuRF-1. |
| 6867 | 23437325 | Under in vitro conditions of hormonal or fatty acid-induced insulin resistance, PMI5011 improves insulin signaling and reduces Atrogin-1 and MuRF-1 protein levels. |
| 6868 | 23437325 | In the KK-A(y) murine model of type 2 diabetes, skeletal muscle ubiquitylation and proteasome activity is inhibited and Atrogin-1 and MuRF-1 expression is decreased by PMI5011. |
| 6869 | 23437325 | PMI5011-mediated changes in the ubiquitin-proteasome system in vivo correlate with increased phosphorylation of Akt and FoxO3a and increased myofiber size. |
| 6870 | 23437325 | The changes in Atrogin-1 and MuRF-1 expression, ubiquitin-proteasome activity and myofiber size modulated by PMI5011 in the presence of insulin resistance indicate the botanical extract PMI5011 may have therapeutic potential in the preservation of muscle mass in type 2 diabetes. |
| 6871 | 23442249 | In ZDFs, hemin administration increased HO activity; normalized glycemia; potentiated insulin signaling by enhancing insulin receptor substrate 1(IRS-1), phosphatidylinositol-3-kinase (PI3K), and protein kinase B (PKB)/Akt; suppressed pericardial adiposity, cardiac hypertrophy, and left ventricular longitudinal muscle fiber thickness, a pathophysiological feature of cardiomyocyte hypertrophy; and correspondingly reduced systolic blood pressure, total peripheral resistance, and pro-inflammatory/oxidative mediators, including nuclear factor κB (NF-κB), cJNK, c-Jun-N-terminal kinase (cJNK), endothelin (ET-1), tumor necrosis factor α (TNF-α), interleukin (IL)-6, IL-1β, activating protein 1 (AP-1), and 8-isoprostane, whereas the HO inhibitor, stannous mesoporphyrin, nullified the effects. |
| 6872 | 23442249 | Because NF-κB activates TNFα, IL-6, and IL-1β and TNF-α, cJNK, and AP-1 impair insulin signaling, the high levels of these cytokines in obesity/diabetes would create a vicious cycle that, together with 8-isoprostane and ET-1, exacerbates cardiac injury, compromising cardiac function. |
| 6873 | 23442249 | Therefore, the concomitant reduction of pro-inflammatory cytokines and macrophage infiltration coupled to increased expressions of IRS-1, PI3K, and PKB may account for enhanced glucose metabolism and amelioration of cardiac injury and function in diabetic cardiomyopathy. |
| 6874 | 23442249 | In ZDFs, hemin administration increased HO activity; normalized glycemia; potentiated insulin signaling by enhancing insulin receptor substrate 1(IRS-1), phosphatidylinositol-3-kinase (PI3K), and protein kinase B (PKB)/Akt; suppressed pericardial adiposity, cardiac hypertrophy, and left ventricular longitudinal muscle fiber thickness, a pathophysiological feature of cardiomyocyte hypertrophy; and correspondingly reduced systolic blood pressure, total peripheral resistance, and pro-inflammatory/oxidative mediators, including nuclear factor κB (NF-κB), cJNK, c-Jun-N-terminal kinase (cJNK), endothelin (ET-1), tumor necrosis factor α (TNF-α), interleukin (IL)-6, IL-1β, activating protein 1 (AP-1), and 8-isoprostane, whereas the HO inhibitor, stannous mesoporphyrin, nullified the effects. |
| 6875 | 23442249 | Because NF-κB activates TNFα, IL-6, and IL-1β and TNF-α, cJNK, and AP-1 impair insulin signaling, the high levels of these cytokines in obesity/diabetes would create a vicious cycle that, together with 8-isoprostane and ET-1, exacerbates cardiac injury, compromising cardiac function. |
| 6876 | 23442249 | Therefore, the concomitant reduction of pro-inflammatory cytokines and macrophage infiltration coupled to increased expressions of IRS-1, PI3K, and PKB may account for enhanced glucose metabolism and amelioration of cardiac injury and function in diabetic cardiomyopathy. |
| 6877 | 23453973 | We then treated glucose-replete and -depleted cells with SB415286, U0126, LY294 and rapamycin to inhibit GSK3, MEK1/2, PI3K and mTOR, respectively. |
| 6878 | 23454256 | Interleukin-1 has opposing effects on connective tissue growth factor and tenascin-C expression in human cardiac fibroblasts. |
| 6879 | 23454256 | We investigated the effects of pro-inflammatory cytokines on matricellular protein expression in cultured human CF. cDNA array analysis of matricellular proteins revealed that interleukin-1α (IL-1α, 10ng/ml, 6h) down-regulated connective tissue growth factor (CTGF/CCN2) mRNA by 80% and up-regulated tenascin-C (TNC) mRNA levels by 10-fold in human CF, without affecting expression of thrombospondins 1-3, osteonectin or osteopontin. |
| 6880 | 23454256 | In contrast, tumor necrosis factor α (TNFα) did not modulate CCN2 expression and had only a modest stimulatory effect on TNC levels. |
| 6881 | 23454256 | Signaling pathway inhibitor studies suggested an important role for the p38 MAPK pathway in suppressing CCN2 expression in response to IL-1α. |
| 6882 | 23454256 | In contrast, multiple signaling pathways (p38, JNK, PI3K/Akt and NFκB) contributed to IL-1α-induced TNC expression. |
| 6883 | 23454256 | In conclusion, IL-1α reduced CCN2 expression and increased TNC expression in human CF. |
| 6884 | 23455320 | Activation of PDK-1 maintains mouse embryonic stem cell self-renewal in a PKB-dependent manner. |
| 6885 | 23455320 | Paling et al. reported that the inhibition of PI3K led to a reduction in the ability of leukemia inhibitory factor to maintain self-renewal, causing cells to differentiate. |
| 6886 | 23455320 | By using a modified Flp recombinase system, we expressed activated alleles of 3-phosphoinositide-dependent protein kinase-1 and protein kinase B to create stable, isogenic ES cell lines to further study the role of the PI3K signaling pathway in stem cell fate determination. |
| 6887 | 23455320 | Activation of PDK-1 maintains mouse embryonic stem cell self-renewal in a PKB-dependent manner. |
| 6888 | 23455320 | Paling et al. reported that the inhibition of PI3K led to a reduction in the ability of leukemia inhibitory factor to maintain self-renewal, causing cells to differentiate. |
| 6889 | 23455320 | By using a modified Flp recombinase system, we expressed activated alleles of 3-phosphoinositide-dependent protein kinase-1 and protein kinase B to create stable, isogenic ES cell lines to further study the role of the PI3K signaling pathway in stem cell fate determination. |
| 6890 | 23456362 | In the presence of antioxidants, blockers of the insulin, and IGF-I receptors, and a phosphatidylinositol 3-kinase inhibitor, the insulin-mediated DNA damage was reduced. |
| 6891 | 23456362 | Phosphorylation of protein kinase B (PKB or AKT) was increased and p53 accumulated. |
| 6892 | 23456362 | In kidneys from healthy, lean ZDF rats, which were infused with insulin to yield normal or high blood insulin levels, while keeping blood glucose levels constant, the amounts of ROS and the tumor protein (p53) were elevated in the high-insulin group compared with the control level group. |
| 6893 | 23462796 | Imatinib mesilate-induced phosphatidylinositol 3-kinase signalling and improved survival in insulin-producing cells: role of Src homology 2-containing inositol 5'-phosphatase interaction with c-Abl. |
| 6894 | 23493574 | miRNA-93 inhibits GLUT4 and is overexpressed in adipose tissue of polycystic ovary syndrome patients and women with insulin resistance. |
| 6895 | 23493574 | In AT, analysis of the IRS/PI3-K/AKT pathway signaling components identified only GLUT4 expression to be significantly lower in PCOS patients and in control subjects with IR. |
| 6896 | 23493574 | We examined the role of miRNAs, particularly in the regulation of GLUT4, the insulin-sensitive glucose transporter, in the AT of PCOS and matched control subjects. |
| 6897 | 23493574 | GLUT4 is a highly predicted target for miR-93, while miR-133 and miR-223 have been demonstrated to regulate GLUT4 expression in cardiomyocytes. |
| 6898 | 23493574 | Expression of miR-93 revealed a strong correlation between the homeostasis model assessment of IR in vivo values and GLUT4 and miR-93 but not miR-133 and -223 expression in human AT. |
| 6899 | 23493574 | Overexpression of miR-93 resulted in downregulation of GLUT4 gene expression in adipocytes through direct targeting of the GLUT4 3'UTR, while inhibition of miR-93 activity led to increased GLUT4 expression. |
| 6900 | 23493574 | These results point to a novel mechanism for regulating insulin-stimulated glucose uptake via miR-93 and demonstrate upregulated miR-93 expression in all PCOS, and in non-PCOS women with IR, possibly accounting for the IR of the syndrome. |
| 6901 | 23497782 | Vaspin attenuates high glucose-induced vascular smooth muscle cells proliferation and chemokinesis by inhibiting the MAPK, PI3K/Akt, and NF-κB signaling pathways. |
| 6902 | 23500140 | Ubiquitin C-terminal hydrolase-L5 is required for high glucose-induced transforming growth factor-β receptor I expression and hypertrophy in mesangial cells. |
| 6903 | 23500140 | Type 1 TGF-β receptor (TGF-βR1) is degraded by Smad7-dependent ubiquitination-proteasomal pathway, which is deubiquitinated by ubiquitin C-terminal hydrolase-L5 (UCHL5). |
| 6904 | 23500140 | UCHL5 short hairpin RNA (shRNA) was used to knock down UCHL5 while LY294002 and the dominant-negative p85 were used to inhibit phosphatidylinositol-3-kinase (PI3K). |
| 6905 | 23500140 | High glucose also increased UCHL5 protein expression, which was attenuated by LY294002, the dominant-negative p85 and the dominant-negative CREB. |
| 6906 | 23500140 | Additionally, high glucose-induced p21(WAF1), fibronectin protein expression and cell hypertrophy were attenuated by UCHL5 shRNA. |
| 6907 | 23500140 | We conclude that PI3K-dependent UCHL5 is required for high glucose-induced TGF-βR1 protein expression in mesangial cells. |
| 6908 | 23500140 | UCHL5 is also required for high glucose-induced TGF-βR1 protein deubiquitination, p21(WAF1) and fibronectin protein expression and cell hypertrophy. |
| 6909 | 23500140 | Ubiquitin C-terminal hydrolase-L5 is required for high glucose-induced transforming growth factor-β receptor I expression and hypertrophy in mesangial cells. |
| 6910 | 23500140 | Type 1 TGF-β receptor (TGF-βR1) is degraded by Smad7-dependent ubiquitination-proteasomal pathway, which is deubiquitinated by ubiquitin C-terminal hydrolase-L5 (UCHL5). |
| 6911 | 23500140 | UCHL5 short hairpin RNA (shRNA) was used to knock down UCHL5 while LY294002 and the dominant-negative p85 were used to inhibit phosphatidylinositol-3-kinase (PI3K). |
| 6912 | 23500140 | High glucose also increased UCHL5 protein expression, which was attenuated by LY294002, the dominant-negative p85 and the dominant-negative CREB. |
| 6913 | 23500140 | Additionally, high glucose-induced p21(WAF1), fibronectin protein expression and cell hypertrophy were attenuated by UCHL5 shRNA. |
| 6914 | 23500140 | We conclude that PI3K-dependent UCHL5 is required for high glucose-induced TGF-βR1 protein expression in mesangial cells. |
| 6915 | 23500140 | UCHL5 is also required for high glucose-induced TGF-βR1 protein deubiquitination, p21(WAF1) and fibronectin protein expression and cell hypertrophy. |
| 6916 | 23506302 | Maternal supplementation of diabetic mice with thymoquinone protects their offspring from abnormal obesity and diabetes by modulating their lipid profile and free radical production and restoring lymphocyte proliferation via PI3K/AKT signaling. |
| 6917 | 23549408 | Our studies further indicated that 6Cl-TGQ activated IR signaling in cell models and insulin-responsive tissues of mice. 6Cl-TGQ-induced Akt phosphorylation was completely blocked by IR and PI3K inhibitors, while the induced glucose uptake was blocked by the same compounds and a Glut4 inhibitor. |
| 6918 | 23564383 | Insulin induces human acyl-coenzyme A: cholesterol acyltransferase1 gene expression via MAP kinases and CCAAT/enhancer-binding protein α. |
| 6919 | 23564383 | To investigate the relationship between hyperinsulinemia and atherosclerosis, we investigated whether insulin induced ACAT1 gene expression and found that insulin up-regulated ACAT1 mRNA, protein and enzyme activity in human THP-1 cells and THP-1-derived macrophages. |
| 6920 | 23564383 | Moreover, luciferase assays revealed that insulin enhanced the ACAT1 gene P1 promoter activity but not the P7 promoter. |
| 6921 | 23564383 | To explore the molecular mechanisms involved, deletion analysis of the human ACAT1 P1 promoter revealed an insulin response element (IRE) upstream of the P1 promoter (from -603 to -580), EMSA experiments demonstrated that CCAAT/enhancer binding protein α(C/EBPα) bound to the P1 promoter IRE. |
| 6922 | 23564383 | Insulin-induced ACAT1 upregulation was blocked by the presence of PD98059 (an inhibitor of extracellular signal-regulated kinase, ERK) and SB203580 (an inhibitor of p38 mitogen-activated protein kinase, p38MAPK) but not by Wortmannin (an inhibitor of phosphatidylinositol 3-kinase, PI3K) or U73122 (an inhibitor of phospholipase C-γ, PLCγ). |
| 6923 | 23564383 | These studies demonstrate that insulin promotes ACAT1 gene expression at the transcriptional level. |
| 6924 | 23564383 | The molecular mechanism of insulin action is mediated via interaction of the functional IRE upstream of the ACAT1 P1 promoter with C/EBPα and is MAPK-dependent. |
| 6925 | 23576171 | Bis(acetylacetonato)-oxovanadium(iv), bis(maltolato)-oxovanadium(iv) and sodium metavanadate induce antilipolytic effects by regulating hormone-sensitive lipase and perilipin via activation of Akt. |
| 6926 | 23576171 | The antilipolytic effects of vanadium compounds were further evidenced by a decrease of the levels of phosphorylated HSL at Ser660 and phosphorylated perilipin, which were counteracted by inhibitors of PI3K or Akt but not by an MEK inhibitor. |
| 6927 | 23576171 | This indicates that though both Akt and ERK pathways are activated by the vanadium compounds, only Akt activation contributes to the antilipolytic effect of the vanadium compounds, without the involvement of ERK activation. |
| 6928 | 23579487 | Cellular insulin resistance disrupts leptin-mediated control of neuronal signaling and transcription. |
| 6929 | 23579487 | Central resistance to the actions of insulin and leptin is associated with the onset of obesity and type 2 diabetes mellitus, whereas leptin and insulin signaling is essential for both glucose and energy homeostasis. |
| 6930 | 23579487 | Although it is known that leptin resistance can lead to attenuated insulin signaling, whether insulin resistance can lead to or exacerbate leptin resistance is unknown. |
| 6931 | 23579487 | Prolonged insulin exposure was used to induce cellular insulin resistance, and thereafter leptin-mediated regulation of signal transduction and gene expression was assessed. |
| 6932 | 23579487 | Leptin directly repressed agouti-related peptide mRNA levels but induced urocortin-2, insulin receptor substrate (IRS)-1, IRS2, and IR transcription, through leptin-mediated phosphatidylinositol 3-kinase/Akt activation. |
| 6933 | 23579487 | Neuronal insulin resistance, as assessed by attenuated Akt phosphorylation, blocked leptin-mediated signal transduction and agouti-related peptide, urocortin-2, IRS1, IRS2, and insulin receptor synthesis. |
| 6934 | 23579487 | Insulin resistance caused a substantial decrease in insulin receptor protein levels, forkhead box protein 1 phosphorylation, and an increase in suppressor of cytokine signaling 3 protein levels. |
| 6935 | 23579487 | Cellular insulin resistance may cause or exacerbate neuronal leptin resistance and, by extension, obesity. |
| 6936 | 23579487 | This study provides improved understanding of the complex cellular crosstalk between insulin-leptin signal transduction that is disrupted during neuronal insulin resistance. |
| 6937 | 23595988 | Treatment with l-3,5,3-triiodothyronine increases the association of TRα with the p85α subunit of phosphatidylinositol 3-kinase (PI3K), leading to the phosphorylation and activation of Akt and the expression of Pdx1, Ngn3, and MafA in purified acinar cells. |
| 6938 | 23595988 | The inhibition of p85α expression by siRNA or the inhibition of PI3K by LY294002 prevents the expression of Pdx1, Ngn3, and MafA and the reprogramming to insulin-producing cells. |
| 6939 | 23595988 | Treatment with l-3,5,3-triiodothyronine increases the association of TRα with the p85α subunit of phosphatidylinositol 3-kinase (PI3K), leading to the phosphorylation and activation of Akt and the expression of Pdx1, Ngn3, and MafA in purified acinar cells. |
| 6940 | 23595988 | The inhibition of p85α expression by siRNA or the inhibition of PI3K by LY294002 prevents the expression of Pdx1, Ngn3, and MafA and the reprogramming to insulin-producing cells. |
| 6941 | 23617393 | Transforming growth factor-β1 and bone morphogenetic protein-7 (BMP7) have been shown to induce DN-like changes in the kidney and protect the kidney from such changes, respectively. |
| 6942 | 23617393 | BMP7 treatment of human kidney proximal tubule epithelial cells (HK-2 cells) increases IRS2 transcription. |
| 6943 | 23617393 | In addition, BMP7 treatment of HK-2 cells induces an electrophoretic shift in IRS2 migration on SDS/PAGE, and increased association with phosphatidylinositol-3-kinase, probably due to increased tyrosine/serine phosphorylation. |
| 6944 | 23617393 | These data show that IRS2 is expressed in the kidney epithelium and may play a role in the downstream protective events triggered by BMP7 in the kidney. |
| 6945 | 23624822 | Crude extract of Ceriporia lacerata has a protective effect on dexamethasone-induced cytotoxicity in INS-1 cells via the modulation of PI3K/PKB activity. |
| 6946 | 23624822 | Moreover, CLCE treatment inhibited Dex-induced protein kinase B (PKB) dephosphorylation without affecting Dex-induced extracellular signal-regulated protein kinase-1/2 dephosphorylation and MKP-1 upregulation. |
| 6947 | 23624822 | Importantly, the protective effect of CLCE on Dex-induced cytotoxicity in INS-1 cells was attenuated by LY294002, an inhibitor of PI3K/PKB. |
| 6948 | 23624822 | Collectively, these findings demonstrate for the first time the ability of CLCE to specifically protect INS-1 cells from Dex-induced cytotoxicity through the modulation of the PI3K/PKB pathway. |
| 6949 | 23624822 | Crude extract of Ceriporia lacerata has a protective effect on dexamethasone-induced cytotoxicity in INS-1 cells via the modulation of PI3K/PKB activity. |
| 6950 | 23624822 | Moreover, CLCE treatment inhibited Dex-induced protein kinase B (PKB) dephosphorylation without affecting Dex-induced extracellular signal-regulated protein kinase-1/2 dephosphorylation and MKP-1 upregulation. |
| 6951 | 23624822 | Importantly, the protective effect of CLCE on Dex-induced cytotoxicity in INS-1 cells was attenuated by LY294002, an inhibitor of PI3K/PKB. |
| 6952 | 23624822 | Collectively, these findings demonstrate for the first time the ability of CLCE to specifically protect INS-1 cells from Dex-induced cytotoxicity through the modulation of the PI3K/PKB pathway. |
| 6953 | 23624822 | Crude extract of Ceriporia lacerata has a protective effect on dexamethasone-induced cytotoxicity in INS-1 cells via the modulation of PI3K/PKB activity. |
| 6954 | 23624822 | Moreover, CLCE treatment inhibited Dex-induced protein kinase B (PKB) dephosphorylation without affecting Dex-induced extracellular signal-regulated protein kinase-1/2 dephosphorylation and MKP-1 upregulation. |
| 6955 | 23624822 | Importantly, the protective effect of CLCE on Dex-induced cytotoxicity in INS-1 cells was attenuated by LY294002, an inhibitor of PI3K/PKB. |
| 6956 | 23624822 | Collectively, these findings demonstrate for the first time the ability of CLCE to specifically protect INS-1 cells from Dex-induced cytotoxicity through the modulation of the PI3K/PKB pathway. |
| 6957 | 23634778 | Leptin, resistin and visfatin: the missing link between endocrine metabolic disorders and immunity. |
| 6958 | 23634778 | Additionally, adipose tissue-secreted hormones such as leptin, visfatin, resistin, apelin, omentin, sex steroids, and various growth factors are now regarded as a functional part of the endocrine system. |
| 6959 | 23634778 | In obese and diabetic conditions, leptin deficiency inhibited the Jak/Stat3/PI3K and insulin pathways. |
| 6960 | 23643895 | Three genes were consistently increased at these time points; c-Jun, Jun-B and the chemokine CXCL-1. |
| 6961 | 23643895 | We have previously shown that cholesterol stimulation leads to PI3K/Akt phosphorylation, and now demonstrated that cholesterol inhibits ERK1/2 phosphorylation; both effects reversed when cholesterol is depleted from lipid rafts using methyl-β-cyclodextrin (MBCD). |
| 6962 | 23643895 | Specific inhibition of p-Akt by wortmannin did not affect cholesterol's stimulation of the expression of c-Jun and Jun-B, however the vanadate effect of increasing p-ERK1/2, inhibited c-Jun expression, specifically, and the MBCD effect of increasing p-ERK and inhibiting p-Akt reduced c-Jun expression. |
| 6963 | 23652775 | In addition, treatment with CZE resulted in a significant increase in alkaline phosphatase (ALP) activity and collagen content, as well as in the expression of genes associated with osteoblast differentiation [ALP, collagen, osteopontin (OPN), osteoprotegerin (OPG), bone sialoprotein (BSP), osteocalcin (OC) and bone morphogenetic protein (BMP)2, BMP4 and BMP7]. |
| 6964 | 23652775 | In mechanistic studies of the antioxidative potential of CZE, we found that CZE reversed the dRib-induced decrease in the expression of phosphatidylinositol 3-kinase (PI3K) and protein kinase B (AKT)1 and AKT2 genes, which are master regulators of survival-related signaling pathways. |
| 6965 | 23652775 | CZE also upregulated the gene expression of the antioxidant enzymes, superoxide dismutase (SOD)2, SOD3 and glutathione peroxidase 4 (GPx4), which was inhibited by dRib. |
| 6966 | 23688574 | Activation of μ-opioid receptor (MOR) could result in reversal of the impairment of insulin-stimulated glucose disposal in genetically obese Zucker rats via exercise training. |
| 6967 | 23688574 | This improvement of insulin resistance was associated with an elevation of circulating β-endorphin to ameliorate the post-receptor insulin signaling cascade, including downstream effectors of the phosphatidylinositol 3-kinase (PI3-kinase) signaling pathway. |
| 6968 | 23688574 | In insulin resistant rats, Loperamide treatment effected on the insulin receptor substrate (IRS)-1/PI3-kinase/Akt signaling cascade and subsequent insulin-stimulated glucose transport trafficking on skeletal muscle, which were all suppressed by MOR antagonism. |
| 6969 | 23688574 | In addition, induction of insulin resistance by the intake of high fructose is more rapid in MOR knockout mice than in wild-type mice. |
| 6970 | 23688574 | Improvements in insulin sensitivity through the peripheral MOR activation overcoming defects related to the post-receptor in IRS-1-associated PI3-kinase step have been defined. |
| 6971 | 23688574 | Opioid receptor activation, especially of the μ-subtype, may provide merits in the amelioration of defective insulin action. |
| 6972 | 23688574 | Atypical zeta (ζ) isoform of protein kinase C serves as a factor that integrates with peripheral MOR pathway and insulin signals for glucose utilization. |
| 6973 | 23688574 | The developments call new insights into the chemical compounds and/or herbal products that might enhance opioid peptide secretion and/or stimulate MOR in peripheral insulin-sensitive tissues to serve as potential agents or adjuvants for helping the glucose metabolism. |
| 6974 | 23688574 | In the present review, we update these topics and discuss the concept of targeting peripheral MOR pathway for the treatment of insulin resistance. |
| 6975 | 23708729 | The regulation of autophagy by nutrient signals involves a complex network of proteins that include mammalian target of rapamycin, the class III phosphatidylinositol-3 kinase/Beclin 1 complex, and two ubiquitin-like conjugation systems. |
| 6976 | 23747931 | N-Acetylcysteine and allopurinol up-regulated the Jak/STAT3 and PI3K/Akt pathways via adiponectin and attenuated myocardial postischemic injury in diabetes. |
| 6977 | 23747931 | We postulated that NAC and ALP attenuated diabetic MI/R injury by up-regulating phosphatidylinositol 3-kinase/Akt (PI3K/Akt) and Janus kinase 2/signal transducer and activator of transcription-3 (JAK2/STAT3) pathways subsequent to adiponectin (APN) activation. |
| 6978 | 23747931 | D rats displayed larger infarct size accompanied by decreased phosphorylation of Akt, STAT3 and decreased cardiac nitric oxide (NO) and APN levels. |
| 6979 | 23747931 | NAC and ALP decreased MI/R injury in D rats, enhanced phosphorylation of Akt and STAT3, and increased NO and APN. |
| 6980 | 23747931 | High glucose and hypoxia/reoxygenation exposure induced cell death and Akt and STAT3 inactivation in cultured cardiomyocytes, which were prevented by NAC and ALP. |
| 6981 | 23747931 | The PI3K inhibitor wortmannin and Jak2 inhibitor AG490 abolished the protection of NAC and ALP. |
| 6982 | 23747931 | Similarly, APN restored posthypoxic Akt and STAT3 activation and decreased cell death in cardiomyocytes. |
| 6983 | 23747931 | Gene silencing with AdipoR2 siRNA or STAT3 siRNA but not AdipoR1 siRNA abolished the protection of NAC and ALP. |
| 6984 | 23747931 | In conclusion, NAC and ALP prevented diabetic MI/R injury through PI3K/Akt and Jak2/STAT3 and cardiac APN may serve as a mediator via AdipoR2 in this process. |
| 6985 | 23747931 | N-Acetylcysteine and allopurinol up-regulated the Jak/STAT3 and PI3K/Akt pathways via adiponectin and attenuated myocardial postischemic injury in diabetes. |
| 6986 | 23747931 | We postulated that NAC and ALP attenuated diabetic MI/R injury by up-regulating phosphatidylinositol 3-kinase/Akt (PI3K/Akt) and Janus kinase 2/signal transducer and activator of transcription-3 (JAK2/STAT3) pathways subsequent to adiponectin (APN) activation. |
| 6987 | 23747931 | D rats displayed larger infarct size accompanied by decreased phosphorylation of Akt, STAT3 and decreased cardiac nitric oxide (NO) and APN levels. |
| 6988 | 23747931 | NAC and ALP decreased MI/R injury in D rats, enhanced phosphorylation of Akt and STAT3, and increased NO and APN. |
| 6989 | 23747931 | High glucose and hypoxia/reoxygenation exposure induced cell death and Akt and STAT3 inactivation in cultured cardiomyocytes, which were prevented by NAC and ALP. |
| 6990 | 23747931 | The PI3K inhibitor wortmannin and Jak2 inhibitor AG490 abolished the protection of NAC and ALP. |
| 6991 | 23747931 | Similarly, APN restored posthypoxic Akt and STAT3 activation and decreased cell death in cardiomyocytes. |
| 6992 | 23747931 | Gene silencing with AdipoR2 siRNA or STAT3 siRNA but not AdipoR1 siRNA abolished the protection of NAC and ALP. |
| 6993 | 23747931 | In conclusion, NAC and ALP prevented diabetic MI/R injury through PI3K/Akt and Jak2/STAT3 and cardiac APN may serve as a mediator via AdipoR2 in this process. |
| 6994 | 23747931 | N-Acetylcysteine and allopurinol up-regulated the Jak/STAT3 and PI3K/Akt pathways via adiponectin and attenuated myocardial postischemic injury in diabetes. |
| 6995 | 23747931 | We postulated that NAC and ALP attenuated diabetic MI/R injury by up-regulating phosphatidylinositol 3-kinase/Akt (PI3K/Akt) and Janus kinase 2/signal transducer and activator of transcription-3 (JAK2/STAT3) pathways subsequent to adiponectin (APN) activation. |
| 6996 | 23747931 | D rats displayed larger infarct size accompanied by decreased phosphorylation of Akt, STAT3 and decreased cardiac nitric oxide (NO) and APN levels. |
| 6997 | 23747931 | NAC and ALP decreased MI/R injury in D rats, enhanced phosphorylation of Akt and STAT3, and increased NO and APN. |
| 6998 | 23747931 | High glucose and hypoxia/reoxygenation exposure induced cell death and Akt and STAT3 inactivation in cultured cardiomyocytes, which were prevented by NAC and ALP. |
| 6999 | 23747931 | The PI3K inhibitor wortmannin and Jak2 inhibitor AG490 abolished the protection of NAC and ALP. |
| 7000 | 23747931 | Similarly, APN restored posthypoxic Akt and STAT3 activation and decreased cell death in cardiomyocytes. |
| 7001 | 23747931 | Gene silencing with AdipoR2 siRNA or STAT3 siRNA but not AdipoR1 siRNA abolished the protection of NAC and ALP. |
| 7002 | 23747931 | In conclusion, NAC and ALP prevented diabetic MI/R injury through PI3K/Akt and Jak2/STAT3 and cardiac APN may serve as a mediator via AdipoR2 in this process. |
| 7003 | 23747931 | N-Acetylcysteine and allopurinol up-regulated the Jak/STAT3 and PI3K/Akt pathways via adiponectin and attenuated myocardial postischemic injury in diabetes. |
| 7004 | 23747931 | We postulated that NAC and ALP attenuated diabetic MI/R injury by up-regulating phosphatidylinositol 3-kinase/Akt (PI3K/Akt) and Janus kinase 2/signal transducer and activator of transcription-3 (JAK2/STAT3) pathways subsequent to adiponectin (APN) activation. |
| 7005 | 23747931 | D rats displayed larger infarct size accompanied by decreased phosphorylation of Akt, STAT3 and decreased cardiac nitric oxide (NO) and APN levels. |
| 7006 | 23747931 | NAC and ALP decreased MI/R injury in D rats, enhanced phosphorylation of Akt and STAT3, and increased NO and APN. |
| 7007 | 23747931 | High glucose and hypoxia/reoxygenation exposure induced cell death and Akt and STAT3 inactivation in cultured cardiomyocytes, which were prevented by NAC and ALP. |
| 7008 | 23747931 | The PI3K inhibitor wortmannin and Jak2 inhibitor AG490 abolished the protection of NAC and ALP. |
| 7009 | 23747931 | Similarly, APN restored posthypoxic Akt and STAT3 activation and decreased cell death in cardiomyocytes. |
| 7010 | 23747931 | Gene silencing with AdipoR2 siRNA or STAT3 siRNA but not AdipoR1 siRNA abolished the protection of NAC and ALP. |
| 7011 | 23747931 | In conclusion, NAC and ALP prevented diabetic MI/R injury through PI3K/Akt and Jak2/STAT3 and cardiac APN may serve as a mediator via AdipoR2 in this process. |
| 7012 | 23748164 | Protein kinase Akt, a downstream effector of PI3K, controls a plethora of cellular functions, including gene transcription. |
| 7013 | 23748164 | Accordingly, altered expression of FOXO targets may account for many biological consequences of PI3K/Akt signaling. |
| 7014 | 23748164 | Protein kinase Akt, a downstream effector of PI3K, controls a plethora of cellular functions, including gene transcription. |
| 7015 | 23748164 | Accordingly, altered expression of FOXO targets may account for many biological consequences of PI3K/Akt signaling. |
| 7016 | 23762123 | Upon the intragastric administration in obese insulin-resistant diabetic KKAy mice for 28 days, TLSP, LSP1, and LSP2 all caused a remarkable decrease of fasting blood glucose and significant improvement of insulin resistance and serum lipid metabolism in diabetic mice. |
| 7017 | 23762123 | In addition, liver histological analysis showed that TLSP, LSP1, and LSP2 significantly ameliorated the hepatocyte hypertrophy and decreased the lipid accumulation in the mice liver. |
| 7018 | 23762123 | Further experiments suggested that TLSP, LSP1, and LSP2 effectively inhibited hepatic gluconeogenesis and increased hepatic glycolysis and hepatic glycogen content. |
| 7019 | 23762123 | Furthermore, the mechanistic analysis showed the increased expression of insulin-receptor α subunit, insulin-receptor substrate-1, phosphatidylinositol 3-kinase, and peroxisome proliferators-activated receptors γ . |
| 7020 | 23762123 | These results suggested that TLSP, LSP1, and LSP2 manifest strong antidiabetic activity, therefore hold a great promise for therapeutic application in diabetic therapy and other related metabolic disorders. |
| 7021 | 23788640 | FOG2 protein down-regulation by transforming growth factor-β1-induced microRNA-200b/c leads to Akt kinase activation and glomerular mesangial hypertrophy related to diabetic nephropathy. |
| 7022 | 23788640 | Akt kinase activated by transforming growth factor-β1 (TGF-β) plays an important role in glomerular mesangial hypertrophy. |
| 7023 | 23788640 | Recently, miR-200 and its target FOG2 were reported to regulate the activity of phosphatidylinositol 3-kinase (the upstream activator of Akt) in insulin signaling. |
| 7024 | 23788640 | Here, we show that TGF-β activates Akt in glomerular mesangial cells by inducing miR-200b and miR-200c, both of which target FOG2, an inhibitor of phosphatidylinositol 3-kinase activation. |
| 7025 | 23788640 | FOG2 knockdown by siRNAs in MMC activated Akt and increased the protein content/cell ratio suggesting hypertrophy. |
| 7026 | 23788640 | In addition, down-regulation of FOG2 by miR-200b/c could activate not only Akt but also ERK, which was also through PI3K activation. |
| 7027 | 23788640 | These data suggest a new mechanism for TGF-β-induced Akt activation through FOG2 down-regulation by miR-200b/c, which can lead to glomerular mesangial hypertrophy in the progression of diabetic nephropathy. |
| 7028 | 23788640 | FOG2 protein down-regulation by transforming growth factor-β1-induced microRNA-200b/c leads to Akt kinase activation and glomerular mesangial hypertrophy related to diabetic nephropathy. |
| 7029 | 23788640 | Akt kinase activated by transforming growth factor-β1 (TGF-β) plays an important role in glomerular mesangial hypertrophy. |
| 7030 | 23788640 | Recently, miR-200 and its target FOG2 were reported to regulate the activity of phosphatidylinositol 3-kinase (the upstream activator of Akt) in insulin signaling. |
| 7031 | 23788640 | Here, we show that TGF-β activates Akt in glomerular mesangial cells by inducing miR-200b and miR-200c, both of which target FOG2, an inhibitor of phosphatidylinositol 3-kinase activation. |
| 7032 | 23788640 | FOG2 knockdown by siRNAs in MMC activated Akt and increased the protein content/cell ratio suggesting hypertrophy. |
| 7033 | 23788640 | In addition, down-regulation of FOG2 by miR-200b/c could activate not only Akt but also ERK, which was also through PI3K activation. |
| 7034 | 23788640 | These data suggest a new mechanism for TGF-β-induced Akt activation through FOG2 down-regulation by miR-200b/c, which can lead to glomerular mesangial hypertrophy in the progression of diabetic nephropathy. |
| 7035 | 23788640 | FOG2 protein down-regulation by transforming growth factor-β1-induced microRNA-200b/c leads to Akt kinase activation and glomerular mesangial hypertrophy related to diabetic nephropathy. |
| 7036 | 23788640 | Akt kinase activated by transforming growth factor-β1 (TGF-β) plays an important role in glomerular mesangial hypertrophy. |
| 7037 | 23788640 | Recently, miR-200 and its target FOG2 were reported to regulate the activity of phosphatidylinositol 3-kinase (the upstream activator of Akt) in insulin signaling. |
| 7038 | 23788640 | Here, we show that TGF-β activates Akt in glomerular mesangial cells by inducing miR-200b and miR-200c, both of which target FOG2, an inhibitor of phosphatidylinositol 3-kinase activation. |
| 7039 | 23788640 | FOG2 knockdown by siRNAs in MMC activated Akt and increased the protein content/cell ratio suggesting hypertrophy. |
| 7040 | 23788640 | In addition, down-regulation of FOG2 by miR-200b/c could activate not only Akt but also ERK, which was also through PI3K activation. |
| 7041 | 23788640 | These data suggest a new mechanism for TGF-β-induced Akt activation through FOG2 down-regulation by miR-200b/c, which can lead to glomerular mesangial hypertrophy in the progression of diabetic nephropathy. |
| 7042 | 23788884 | Insulin resistance and hyperinsulinemia lead to increased concentration of insulin-like growth factors, activation of IGF-R receptors, activation of PI3K and Ras-Raf pathways and result in increased cell division. |
| 7043 | 23788884 | The dominant mechanism of action is activation of the AMP-activated protein kinase (AMPK) pathway and inhibition of mTOR protein, the key protein to regulate cell growth, apoptosis, proliferation and protein synthesis. |
| 7044 | 23799024 | Growth differentiation factor 15 (GDF15), a direct target gene of p53, is a multifunctional member of the TGF-β/BMP superfamily. |
| 7045 | 23799024 | In the present study, we revealed that high glucose could induce GDF15 expression and secretion in cultured human umbilical vein endothelial cells in a ROS- and p53-dependent manner. |
| 7046 | 23799024 | Inhibition of high glucose-induced GDF15 expression by siRNA demonstrated that adaptively induced GDF15 played a protective role against high glucose-induced human umbilical vein endothelial cell apoptosis via maintaining the active state of PI3K/Akt/eNOS pathway and attenuating NF-κB/JNK pathway activation. |
| 7047 | 23805528 | [Effect of ashitabe chalcones on the mRNA expression of PI3K and Akt in hepatocytes of rats with diabetes]. |
| 7048 | 23810378 | PIK3R1 mutations cause syndromic insulin resistance with lipoatrophy. |
| 7049 | 23810378 | PIK3R1 encodes the p85α, p55α, and p50α regulatory subunits of class IA phosphatidylinositol 3 kinases (PI3Ks), which are known to play a key role in insulin signaling. |
| 7050 | 23810378 | Functional data from fibroblasts derived from individuals with PIK3R1 mutations showed severe insulin resistance for both proximal and distal PI3K-dependent signaling. |
| 7051 | 23810378 | Our findings extend the genetic causes of severe insulin-resistance syndromes and provide important information with respect to the function of PIK3R1 in normal development and its role in human diseases, including growth delay, Rieger anomaly and other ocular affections, insulin resistance, diabetes, paucity of fat, and ovarian cysts. |
| 7052 | 23810378 | PIK3R1 mutations cause syndromic insulin resistance with lipoatrophy. |
| 7053 | 23810378 | PIK3R1 encodes the p85α, p55α, and p50α regulatory subunits of class IA phosphatidylinositol 3 kinases (PI3Ks), which are known to play a key role in insulin signaling. |
| 7054 | 23810378 | Functional data from fibroblasts derived from individuals with PIK3R1 mutations showed severe insulin resistance for both proximal and distal PI3K-dependent signaling. |
| 7055 | 23810378 | Our findings extend the genetic causes of severe insulin-resistance syndromes and provide important information with respect to the function of PIK3R1 in normal development and its role in human diseases, including growth delay, Rieger anomaly and other ocular affections, insulin resistance, diabetes, paucity of fat, and ovarian cysts. |
| 7056 | 23810379 | This mutation led to impaired interaction between p85α and IRS-1 and reduced AKT-mediated insulin signaling in fibroblasts from affected subjects and in reconstituted Pik3r1-knockout preadipocytes. |
| 7057 | 23810379 | Normal PI3K activity is critical for adipose differentiation and insulin signaling; the mutated PIK3R1 therefore provides a unique link among lipodystrophy, growth, and insulin signaling. |
| 7058 | 23819014 | Although signaling via PI3K, Sirt1, AMPK, ROS, and Nrf2 appeared to play a significant role in the modulation of PAI-1 gene expression under noninflammatory conditions, those signaling components were not involved in mediating the resveratrol effects on PAI-1 production under inflammatory conditions. |
| 7059 | 23826727 | PTEN controls β-cell regeneration in aged mice by regulating cell cycle inhibitor p16ink4a. |
| 7060 | 23826727 | Tissue regeneration diminishes with age, concurrent with declining hormone levels including growth factors such as insulin-like growth factor-1 (IGF-1). |
| 7061 | 23826727 | We studied the regeneration capacity of β-cells in mouse model where PI3K/AKT pathway downstream of insulin/IGF-1 signaling is upregulated by genetic deletion of Pten (phosphatase and tensin homologue deleted on chromosome 10) specifically in insulin-producing cells. |
| 7062 | 23826727 | Using several animal and cell models where we can manipulate PTEN expression, we found that PTEN blocks cell cycle re-entry through a novel pathway leading to an increase in p16(ink4a), a cell cycle inhibitor characterized for its role in cellular senescence/aging. |
| 7063 | 23826727 | A downregulation in p16(ink4a) occurs when PTEN is lost as a result of cyclin D1 induction and the activation of E2F transcription factors. |
| 7064 | 23826727 | The activation of E2F transcriptional factors leads to methylation of p16(ink4a) promoter, an event that is mediated by the upregulation of polycomb protein, Ezh2. |
| 7065 | 23826727 | These analyses establish a novel PTEN/cyclin D1/E2F/Ezh2/p16(ink4a) signaling network responsible for the aging process and provide specific evidence for a molecular paradigm that explain how decline in growth factor signals such as IGF-1 (through PTEN/PI3K signaling) may control regeneration and the lack thereof in aging cells. |
| 7066 | 23826727 | PTEN controls β-cell regeneration in aged mice by regulating cell cycle inhibitor p16ink4a. |
| 7067 | 23826727 | Tissue regeneration diminishes with age, concurrent with declining hormone levels including growth factors such as insulin-like growth factor-1 (IGF-1). |
| 7068 | 23826727 | We studied the regeneration capacity of β-cells in mouse model where PI3K/AKT pathway downstream of insulin/IGF-1 signaling is upregulated by genetic deletion of Pten (phosphatase and tensin homologue deleted on chromosome 10) specifically in insulin-producing cells. |
| 7069 | 23826727 | Using several animal and cell models where we can manipulate PTEN expression, we found that PTEN blocks cell cycle re-entry through a novel pathway leading to an increase in p16(ink4a), a cell cycle inhibitor characterized for its role in cellular senescence/aging. |
| 7070 | 23826727 | A downregulation in p16(ink4a) occurs when PTEN is lost as a result of cyclin D1 induction and the activation of E2F transcription factors. |
| 7071 | 23826727 | The activation of E2F transcriptional factors leads to methylation of p16(ink4a) promoter, an event that is mediated by the upregulation of polycomb protein, Ezh2. |
| 7072 | 23826727 | These analyses establish a novel PTEN/cyclin D1/E2F/Ezh2/p16(ink4a) signaling network responsible for the aging process and provide specific evidence for a molecular paradigm that explain how decline in growth factor signals such as IGF-1 (through PTEN/PI3K signaling) may control regeneration and the lack thereof in aging cells. |
| 7073 | 23827786 | However, it's still not clear whether mTOR, another main gene in PI3K/Akt pathway, is also involved in the renal lipogenesis of diabetes. |
| 7074 | 23827786 | In the present study, it was revealed that the phosphorylation of mTOR was up-regulated in the renal tubular cells of diabetic rats, followed by the over-expression of SREBP-1, ADRP and lipogenesis. |
| 7075 | 23827786 | Again, high glucose increased the expression of phospho-mTOR accompanied with SREBP-1 and ADRP up-regulation and lipid accumulation in HKC cells. |
| 7076 | 23834149 | In this paper, an overview was depicted about the role of following miRNAs in pancreatic development and insulin secretion (miR-375, miR-7, miR-124a2, miR-195, miR-126, miR-9, miR-96, miR-34a); insulingrowth factor-1 receptor expression (miR-7, miR-139, miR-145, miR-1); the diabetes-associated pancreatic cancer pathway genes such as IRS, PI3K, AKT/PKB (miR-128a, miR-19a, miR-21, miR-29 a/b/c); mTOR protein regulation (miR- 99, miR-21, miR-126, and miR-146a) etc. |
| 7077 | 23834149 | At last, we have also explained the role of miRNAs in diagnostic marker (miR- 200, miR-21, miR-103, miR-107, and miR-155) and as a therapeutic modulator (miR-34, miR-21, miR-221, and miR-101) in pancreatic cancer. |
| 7078 | 23840461 | Tectorigenin Attenuates Palmitate-Induced Endothelial Insulin Resistance via Targeting ROS-Associated Inflammation and IRS-1 Pathway. |
| 7079 | 23840461 | Palmitic acid (PA) was chosen as a stimulant to induce ROS production in endothelial cells and successfully established insulin resistance evidenced by the specific impairment of insulin PI3K signaling. |
| 7080 | 23840461 | Moreover, tectorigenin presented strong inhibition effect on ROS-associated inflammation, as TNF-α and IL-6 production in endothelial cells was greatly reduced with suppression of IKKβ/NF-κB phosphorylation and JNK activation. |
| 7081 | 23840461 | Tectorigenin also can inhibit inflammation-stimulated IRS-1 serine phosphorylation and restore the impaired insulin PI3K signaling, leading to a decreased NO production. |
| 7082 | 23840461 | Meanwhile, tectorigenin down-regulated endothelin-1 and vascular cell adhesion molecule-1 overexpression, and restored the loss of insulin-mediated vasodilation in rat aorta. |
| 7083 | 23840461 | These findings suggested that tectorigenin could inhibit ROS-associated inflammation and ameliorated endothelial dysfunction implicated in insulin resistance through regulating IRS-1 function. |
| 7084 | 23840461 | Tectorigenin Attenuates Palmitate-Induced Endothelial Insulin Resistance via Targeting ROS-Associated Inflammation and IRS-1 Pathway. |
| 7085 | 23840461 | Palmitic acid (PA) was chosen as a stimulant to induce ROS production in endothelial cells and successfully established insulin resistance evidenced by the specific impairment of insulin PI3K signaling. |
| 7086 | 23840461 | Moreover, tectorigenin presented strong inhibition effect on ROS-associated inflammation, as TNF-α and IL-6 production in endothelial cells was greatly reduced with suppression of IKKβ/NF-κB phosphorylation and JNK activation. |
| 7087 | 23840461 | Tectorigenin also can inhibit inflammation-stimulated IRS-1 serine phosphorylation and restore the impaired insulin PI3K signaling, leading to a decreased NO production. |
| 7088 | 23840461 | Meanwhile, tectorigenin down-regulated endothelin-1 and vascular cell adhesion molecule-1 overexpression, and restored the loss of insulin-mediated vasodilation in rat aorta. |
| 7089 | 23840461 | These findings suggested that tectorigenin could inhibit ROS-associated inflammation and ameliorated endothelial dysfunction implicated in insulin resistance through regulating IRS-1 function. |
| 7090 | 23862686 | Akt regulates TPP1 homodimerization and telomere protection. |
| 7091 | 23862686 | The phosphatidylinositol 3-kinase (PI3-K)/Akt (also known as PKB) pathway, one of the best characterized growth signaling cascades, regulates a variety of cellular function including cell proliferation, survival, metabolism, and DNA repair, and dysregulation of PI3-K/Akt signaling has been linked to aging and diseases such as cancer and diabetes. |
| 7092 | 23862686 | Telomere damage and reduced TPP1 dimerization as a result of Akt inhibition was also accompanied by diminished recruitment of TPP1 and POT1 to the telomeres. |
| 7093 | 23880101 | The phosphatidylinositol 3 kinase/protein kinase B (PI3K/Akt) pathway mediates the high-glucose-induced lipid accumulation in the renal tubular cells in diabetes. |
| 7094 | 23880101 | Inhibiting GSK-3β activity using TWS119 increased the sterol regulatory element binding protein-1 (SREBP-1) content and lipogenesis in renal tubular cells. |
| 7095 | 23894818 | [Effects of retinol binding protein 4 knockdown on the PI3K/Akt pathways in porcine adipocytes]. |
| 7096 | 23894818 | Retinol-binding protein 4 (RBP4) is adipocyte-derived secreted adipokines and elevated RBP4 expression level was closely related to insulin resistance and type II diabetes mellitus. |
| 7097 | 23894818 | RBP4 interference efficiency and the gene expression of each treatment groups in PI3K/Akt pathways were examined by QRT-PCR and Western blotting. |
| 7098 | 23894818 | Furthermore, no matter under insulin stimulation or insulin resistance, RBP4 knockdown significantly increased the mRNA expressions of AKT2, PI3K, GLUT4 and IRS1 compared with the control. |
| 7099 | 23894818 | The protein phosphorylate levels of AKT2, PI3K, IRS1 arised, meanwhile enhanced the AKT2, PI3K, GLUT4 total protein expressions. |
| 7100 | 23894818 | Collectively, knockdown of RBP4 increased the insulin sensitivity through upregulated PI3K/Akt pathways related factors' expression and phosphorylation in porcine adipocytes. |
| 7101 | 23894818 | [Effects of retinol binding protein 4 knockdown on the PI3K/Akt pathways in porcine adipocytes]. |
| 7102 | 23894818 | Retinol-binding protein 4 (RBP4) is adipocyte-derived secreted adipokines and elevated RBP4 expression level was closely related to insulin resistance and type II diabetes mellitus. |
| 7103 | 23894818 | RBP4 interference efficiency and the gene expression of each treatment groups in PI3K/Akt pathways were examined by QRT-PCR and Western blotting. |
| 7104 | 23894818 | Furthermore, no matter under insulin stimulation or insulin resistance, RBP4 knockdown significantly increased the mRNA expressions of AKT2, PI3K, GLUT4 and IRS1 compared with the control. |
| 7105 | 23894818 | The protein phosphorylate levels of AKT2, PI3K, IRS1 arised, meanwhile enhanced the AKT2, PI3K, GLUT4 total protein expressions. |
| 7106 | 23894818 | Collectively, knockdown of RBP4 increased the insulin sensitivity through upregulated PI3K/Akt pathways related factors' expression and phosphorylation in porcine adipocytes. |
| 7107 | 23894818 | [Effects of retinol binding protein 4 knockdown on the PI3K/Akt pathways in porcine adipocytes]. |
| 7108 | 23894818 | Retinol-binding protein 4 (RBP4) is adipocyte-derived secreted adipokines and elevated RBP4 expression level was closely related to insulin resistance and type II diabetes mellitus. |
| 7109 | 23894818 | RBP4 interference efficiency and the gene expression of each treatment groups in PI3K/Akt pathways were examined by QRT-PCR and Western blotting. |
| 7110 | 23894818 | Furthermore, no matter under insulin stimulation or insulin resistance, RBP4 knockdown significantly increased the mRNA expressions of AKT2, PI3K, GLUT4 and IRS1 compared with the control. |
| 7111 | 23894818 | The protein phosphorylate levels of AKT2, PI3K, IRS1 arised, meanwhile enhanced the AKT2, PI3K, GLUT4 total protein expressions. |
| 7112 | 23894818 | Collectively, knockdown of RBP4 increased the insulin sensitivity through upregulated PI3K/Akt pathways related factors' expression and phosphorylation in porcine adipocytes. |
| 7113 | 23894818 | [Effects of retinol binding protein 4 knockdown on the PI3K/Akt pathways in porcine adipocytes]. |
| 7114 | 23894818 | Retinol-binding protein 4 (RBP4) is adipocyte-derived secreted adipokines and elevated RBP4 expression level was closely related to insulin resistance and type II diabetes mellitus. |
| 7115 | 23894818 | RBP4 interference efficiency and the gene expression of each treatment groups in PI3K/Akt pathways were examined by QRT-PCR and Western blotting. |
| 7116 | 23894818 | Furthermore, no matter under insulin stimulation or insulin resistance, RBP4 knockdown significantly increased the mRNA expressions of AKT2, PI3K, GLUT4 and IRS1 compared with the control. |
| 7117 | 23894818 | The protein phosphorylate levels of AKT2, PI3K, IRS1 arised, meanwhile enhanced the AKT2, PI3K, GLUT4 total protein expressions. |
| 7118 | 23894818 | Collectively, knockdown of RBP4 increased the insulin sensitivity through upregulated PI3K/Akt pathways related factors' expression and phosphorylation in porcine adipocytes. |
| 7119 | 23894818 | [Effects of retinol binding protein 4 knockdown on the PI3K/Akt pathways in porcine adipocytes]. |
| 7120 | 23894818 | Retinol-binding protein 4 (RBP4) is adipocyte-derived secreted adipokines and elevated RBP4 expression level was closely related to insulin resistance and type II diabetes mellitus. |
| 7121 | 23894818 | RBP4 interference efficiency and the gene expression of each treatment groups in PI3K/Akt pathways were examined by QRT-PCR and Western blotting. |
| 7122 | 23894818 | Furthermore, no matter under insulin stimulation or insulin resistance, RBP4 knockdown significantly increased the mRNA expressions of AKT2, PI3K, GLUT4 and IRS1 compared with the control. |
| 7123 | 23894818 | The protein phosphorylate levels of AKT2, PI3K, IRS1 arised, meanwhile enhanced the AKT2, PI3K, GLUT4 total protein expressions. |
| 7124 | 23894818 | Collectively, knockdown of RBP4 increased the insulin sensitivity through upregulated PI3K/Akt pathways related factors' expression and phosphorylation in porcine adipocytes. |
| 7125 | 23900416 | Hindbrain GLP-1 receptor-mediated suppression of food intake requires a PI3K-dependent decrease in phosphorylation of membrane-bound Akt. |
| 7126 | 23900416 | Glucagon-like peptide-1 (GLP-1) receptors (GLP-1R) expressed in the nucleus tractus solitarius (NTS) are physiologically required for the control of feeding. |
| 7127 | 23900416 | Because cAMP/PKA activity can promote PI3K/PIP3-dependent translocation of Akt to the plasma membrane, we hypothesize that hindbrain GLP-1R-mediated control of feeding involves a PI3K-Akt-dependent pathway. |
| 7128 | 23900416 | Importantly, the novel evidence presented here challenges the dogmatic view that PI3K phosphorylation results in an obligatory activation of Akt and instead supports a growing body of literature showing that activation of cAMP/PKA can inhibit Akt phosphorylation at the plasma membrane. |
| 7129 | 23900416 | Behavioral data show that inhibition of hindbrain PI3K activity by a fourth icv administration of LY-294002 (3.07 μg) attenuated the food intake- and body weight-suppressive effects of a fourth icv administration of the GLP-1R agonist exendin-4 (0.3 μg) in rats. |
| 7130 | 23900416 | Immunoblot analyses of ex vivo NTS tissue lysates and in vitro GLP-1R-expressing neurons (GT1-7) support the behavioral findings and show that GLP-1R activation decreases phosphorylation of Akt in a time-dependent fashion. |
| 7131 | 23900416 | Current data reveal the requirement of PI3K activation, PIP3-dependent translocation of Akt to the plasma membrane, and suppression in phosphorylation of membrane-bound Akt to mediate the food intake-suppressive effects of hindbrain GLP-1R activation. |
| 7132 | 23900416 | Hindbrain GLP-1 receptor-mediated suppression of food intake requires a PI3K-dependent decrease in phosphorylation of membrane-bound Akt. |
| 7133 | 23900416 | Glucagon-like peptide-1 (GLP-1) receptors (GLP-1R) expressed in the nucleus tractus solitarius (NTS) are physiologically required for the control of feeding. |
| 7134 | 23900416 | Because cAMP/PKA activity can promote PI3K/PIP3-dependent translocation of Akt to the plasma membrane, we hypothesize that hindbrain GLP-1R-mediated control of feeding involves a PI3K-Akt-dependent pathway. |
| 7135 | 23900416 | Importantly, the novel evidence presented here challenges the dogmatic view that PI3K phosphorylation results in an obligatory activation of Akt and instead supports a growing body of literature showing that activation of cAMP/PKA can inhibit Akt phosphorylation at the plasma membrane. |
| 7136 | 23900416 | Behavioral data show that inhibition of hindbrain PI3K activity by a fourth icv administration of LY-294002 (3.07 μg) attenuated the food intake- and body weight-suppressive effects of a fourth icv administration of the GLP-1R agonist exendin-4 (0.3 μg) in rats. |
| 7137 | 23900416 | Immunoblot analyses of ex vivo NTS tissue lysates and in vitro GLP-1R-expressing neurons (GT1-7) support the behavioral findings and show that GLP-1R activation decreases phosphorylation of Akt in a time-dependent fashion. |
| 7138 | 23900416 | Current data reveal the requirement of PI3K activation, PIP3-dependent translocation of Akt to the plasma membrane, and suppression in phosphorylation of membrane-bound Akt to mediate the food intake-suppressive effects of hindbrain GLP-1R activation. |
| 7139 | 23900416 | Hindbrain GLP-1 receptor-mediated suppression of food intake requires a PI3K-dependent decrease in phosphorylation of membrane-bound Akt. |
| 7140 | 23900416 | Glucagon-like peptide-1 (GLP-1) receptors (GLP-1R) expressed in the nucleus tractus solitarius (NTS) are physiologically required for the control of feeding. |
| 7141 | 23900416 | Because cAMP/PKA activity can promote PI3K/PIP3-dependent translocation of Akt to the plasma membrane, we hypothesize that hindbrain GLP-1R-mediated control of feeding involves a PI3K-Akt-dependent pathway. |
| 7142 | 23900416 | Importantly, the novel evidence presented here challenges the dogmatic view that PI3K phosphorylation results in an obligatory activation of Akt and instead supports a growing body of literature showing that activation of cAMP/PKA can inhibit Akt phosphorylation at the plasma membrane. |
| 7143 | 23900416 | Behavioral data show that inhibition of hindbrain PI3K activity by a fourth icv administration of LY-294002 (3.07 μg) attenuated the food intake- and body weight-suppressive effects of a fourth icv administration of the GLP-1R agonist exendin-4 (0.3 μg) in rats. |
| 7144 | 23900416 | Immunoblot analyses of ex vivo NTS tissue lysates and in vitro GLP-1R-expressing neurons (GT1-7) support the behavioral findings and show that GLP-1R activation decreases phosphorylation of Akt in a time-dependent fashion. |
| 7145 | 23900416 | Current data reveal the requirement of PI3K activation, PIP3-dependent translocation of Akt to the plasma membrane, and suppression in phosphorylation of membrane-bound Akt to mediate the food intake-suppressive effects of hindbrain GLP-1R activation. |
| 7146 | 23900416 | Hindbrain GLP-1 receptor-mediated suppression of food intake requires a PI3K-dependent decrease in phosphorylation of membrane-bound Akt. |
| 7147 | 23900416 | Glucagon-like peptide-1 (GLP-1) receptors (GLP-1R) expressed in the nucleus tractus solitarius (NTS) are physiologically required for the control of feeding. |
| 7148 | 23900416 | Because cAMP/PKA activity can promote PI3K/PIP3-dependent translocation of Akt to the plasma membrane, we hypothesize that hindbrain GLP-1R-mediated control of feeding involves a PI3K-Akt-dependent pathway. |
| 7149 | 23900416 | Importantly, the novel evidence presented here challenges the dogmatic view that PI3K phosphorylation results in an obligatory activation of Akt and instead supports a growing body of literature showing that activation of cAMP/PKA can inhibit Akt phosphorylation at the plasma membrane. |
| 7150 | 23900416 | Behavioral data show that inhibition of hindbrain PI3K activity by a fourth icv administration of LY-294002 (3.07 μg) attenuated the food intake- and body weight-suppressive effects of a fourth icv administration of the GLP-1R agonist exendin-4 (0.3 μg) in rats. |
| 7151 | 23900416 | Immunoblot analyses of ex vivo NTS tissue lysates and in vitro GLP-1R-expressing neurons (GT1-7) support the behavioral findings and show that GLP-1R activation decreases phosphorylation of Akt in a time-dependent fashion. |
| 7152 | 23900416 | Current data reveal the requirement of PI3K activation, PIP3-dependent translocation of Akt to the plasma membrane, and suppression in phosphorylation of membrane-bound Akt to mediate the food intake-suppressive effects of hindbrain GLP-1R activation. |
| 7153 | 23900416 | Hindbrain GLP-1 receptor-mediated suppression of food intake requires a PI3K-dependent decrease in phosphorylation of membrane-bound Akt. |
| 7154 | 23900416 | Glucagon-like peptide-1 (GLP-1) receptors (GLP-1R) expressed in the nucleus tractus solitarius (NTS) are physiologically required for the control of feeding. |
| 7155 | 23900416 | Because cAMP/PKA activity can promote PI3K/PIP3-dependent translocation of Akt to the plasma membrane, we hypothesize that hindbrain GLP-1R-mediated control of feeding involves a PI3K-Akt-dependent pathway. |
| 7156 | 23900416 | Importantly, the novel evidence presented here challenges the dogmatic view that PI3K phosphorylation results in an obligatory activation of Akt and instead supports a growing body of literature showing that activation of cAMP/PKA can inhibit Akt phosphorylation at the plasma membrane. |
| 7157 | 23900416 | Behavioral data show that inhibition of hindbrain PI3K activity by a fourth icv administration of LY-294002 (3.07 μg) attenuated the food intake- and body weight-suppressive effects of a fourth icv administration of the GLP-1R agonist exendin-4 (0.3 μg) in rats. |
| 7158 | 23900416 | Immunoblot analyses of ex vivo NTS tissue lysates and in vitro GLP-1R-expressing neurons (GT1-7) support the behavioral findings and show that GLP-1R activation decreases phosphorylation of Akt in a time-dependent fashion. |
| 7159 | 23900416 | Current data reveal the requirement of PI3K activation, PIP3-dependent translocation of Akt to the plasma membrane, and suppression in phosphorylation of membrane-bound Akt to mediate the food intake-suppressive effects of hindbrain GLP-1R activation. |
| 7160 | 23923576 | Since insulin signaling pathway has been shown to be regulated by nutritional supplements, in the present study, we investigated the possible effects of free amino acids, such as lysine, arginine and alanine and their mixture in modulating the insulin receptor tyrosine kinase (IRTK) and phosphatidyl inositol-3-OH-kinase (PI3K) activities and on the changes in actin dynamics in monocytes (MC), exposed to high glucose concentration (25 mM). |
| 7161 | 23933686 | SGK1 is activated by insulin and growth factors via phosphatidylinositol-3-kinase, 3-phosphoinositide dependent-kinase PDK1, and mTOR. |
| 7162 | 23933686 | NCC, NKCC, NHE1, NHE3, SGLT1, several amino acid transporters) and many ion channels (e.g. |
| 7163 | 23933686 | ENaC, SCN5A, TRPV4-6, Orai1/STIM1, ROMK, KCNE1/KCNQ1, GluR6, CFTR). |
| 7164 | 23933686 | SGK1 further up-regulates a number of enzymes (e.g. glycogen-synthase-kinase-3, ubiquitin-ligase Nedd4-2), and transcription factors (e.g. forkhead-transcription-factor FOXO3a, β-catenin, nuclear-factor-kappa-B NFκB). |
| 7165 | 23934677 | Functional significance of the novel H-RAS gene mutation M72I in a patient with medullary thyroid cancer. |
| 7166 | 23934677 | Though usually sporadic, 1 in 4 cases are of genetic origin, with germinal mutations in the RET proto-oncogene in familial forms and somatic mutations both in RET and in the RAS family genes in sporadic ones.This study aimed to characterize a rare H-RAS sequence variant -M72I- in a patient with sporadic MTC, focusing on its functional significance.Mutation analysis was performed for the RET, N-RAS, K-RAS and H-RAS genes by direct sequencing. |
| 7167 | 23934677 | Western blot analysis was done on 4 thyroid tissues from 1 patient carrying the M72I mutation in H-RAS, 1 with the Q61R mutation in H-RAS, 1 with no RET, H-RAS, K-RAS or N-RAS gene mutations, and 1 normal thyroid, using different antibodies against Erk1/2, phospho-Erk1/2 (Thr202/Tyr204), Akt and phospho-Akt (Ser473). |
| 7168 | 23934677 | Large-scale molecular dynamics simulations were completed for H-RAS wt and H-RAS M72I.Western blot analysis demonstrated that both MAPK and PI3K/Akt pathways were activated in the MTC patient carrying the M72I variant. |
| 7169 | 23934677 | Results of molecular dynamics were consistent with Western blot experiments.The M72I mutation may contribute effectively to proliferation and survival signaling throughout the MAPK and PI3K/Akt pathways. |
| 7170 | 23934677 | Functional significance of the novel H-RAS gene mutation M72I in a patient with medullary thyroid cancer. |
| 7171 | 23934677 | Though usually sporadic, 1 in 4 cases are of genetic origin, with germinal mutations in the RET proto-oncogene in familial forms and somatic mutations both in RET and in the RAS family genes in sporadic ones.This study aimed to characterize a rare H-RAS sequence variant -M72I- in a patient with sporadic MTC, focusing on its functional significance.Mutation analysis was performed for the RET, N-RAS, K-RAS and H-RAS genes by direct sequencing. |
| 7172 | 23934677 | Western blot analysis was done on 4 thyroid tissues from 1 patient carrying the M72I mutation in H-RAS, 1 with the Q61R mutation in H-RAS, 1 with no RET, H-RAS, K-RAS or N-RAS gene mutations, and 1 normal thyroid, using different antibodies against Erk1/2, phospho-Erk1/2 (Thr202/Tyr204), Akt and phospho-Akt (Ser473). |
| 7173 | 23934677 | Large-scale molecular dynamics simulations were completed for H-RAS wt and H-RAS M72I.Western blot analysis demonstrated that both MAPK and PI3K/Akt pathways were activated in the MTC patient carrying the M72I variant. |
| 7174 | 23934677 | Results of molecular dynamics were consistent with Western blot experiments.The M72I mutation may contribute effectively to proliferation and survival signaling throughout the MAPK and PI3K/Akt pathways. |
| 7175 | 23935514 | The s908 mutation leads to a leucine to arginine substitution in the ectodomain of the hepatocyte growth factor (HGF) tyrosine kinase receptor, Met. |
| 7176 | 23935514 | Treatment with PI3K and STAT3 inhibitors, but not with MAPK inhibitors, phenocopies the donut pancreatic defect, further indicating that Met signals through migratory pathways during pancreas development. |
| 7177 | 23954465 | We have previously reported that BBR attenuated H2O2 neurotoxicity via activating the PI3K/Akt/Nrf2-dependent pathway. |
| 7178 | 23954465 | However, AG1024, an inhibitor of insulin growth factor-1 (IGF-1) receptor, significantly abolished BBR protection against high glucose-induced neuronal death. |
| 7179 | 23954465 | BBR also increased Bcl-2 expression and decreased cytochrome c release. |
| 7180 | 23954465 | High glucose down-regulated IGF-1 receptor and phosphorylation of Akt and GSK-3β, the effects of which were attenuated by BBR treatment. |
| 7181 | 23954465 | BBR also activated nuclear erythroid 2-related factor 2 (Nrf2), the key antioxidative transcription factor, which is accompanied with up-regulation of hemeoxygenase-1 (HO-1). |
| 7182 | 23954465 | Results indicated Nrf2 siRNA abolished BBR-induced HO-1, NGF, neurite outgrowth and ROS decrease. |
| 7183 | 23956765 | Panax Quinquefolius Saponin of Stem and Leaf Attenuates Intermittent High Glucose-Induced Oxidative Stress Injury in Cultured Human Umbilical Vein Endothelial Cells via PI3K/Akt/GSK-3 β Pathway. |
| 7184 | 23956765 | In the present study, we investigated the protective effects of PQS against intermittent high glucose-induced oxidative damage on human umbilical vein endothelial cells (HUVECs) and the role of phosphatidylinositol 3-kinase kinase (PI3K)/Akt/GSK-3 β pathway involved. |
| 7185 | 23956765 | These findings suggest that PQS attenuates intermittent-high-glucose-induced oxidative stress injury in HUVECs by PI3K/Akt/GSK-3 β pathway. |
| 7186 | 23956765 | Panax Quinquefolius Saponin of Stem and Leaf Attenuates Intermittent High Glucose-Induced Oxidative Stress Injury in Cultured Human Umbilical Vein Endothelial Cells via PI3K/Akt/GSK-3 β Pathway. |
| 7187 | 23956765 | In the present study, we investigated the protective effects of PQS against intermittent high glucose-induced oxidative damage on human umbilical vein endothelial cells (HUVECs) and the role of phosphatidylinositol 3-kinase kinase (PI3K)/Akt/GSK-3 β pathway involved. |
| 7188 | 23956765 | These findings suggest that PQS attenuates intermittent-high-glucose-induced oxidative stress injury in HUVECs by PI3K/Akt/GSK-3 β pathway. |
| 7189 | 23956765 | Panax Quinquefolius Saponin of Stem and Leaf Attenuates Intermittent High Glucose-Induced Oxidative Stress Injury in Cultured Human Umbilical Vein Endothelial Cells via PI3K/Akt/GSK-3 β Pathway. |
| 7190 | 23956765 | In the present study, we investigated the protective effects of PQS against intermittent high glucose-induced oxidative damage on human umbilical vein endothelial cells (HUVECs) and the role of phosphatidylinositol 3-kinase kinase (PI3K)/Akt/GSK-3 β pathway involved. |
| 7191 | 23956765 | These findings suggest that PQS attenuates intermittent-high-glucose-induced oxidative stress injury in HUVECs by PI3K/Akt/GSK-3 β pathway. |
| 7192 | 23974924 | The long QT interval of type 1 diabetic hearts was shortened by insulin treatment ex vivo, and this effect was blocked by a PI3K inhibitor. |
| 7193 | 23975131 | Jiaotai Pill enhances insulin signaling through phosphatidylinositol 3-kinase pathway in skeletal muscle of diabetic rats. |
| 7194 | 23991359 | Adipose tissue insulin sensitivity and macrophage recruitment: Does PI3K pick the pathway? |
| 7195 | 23991359 | In this mini-review, we focus on a potential role of adipose tissue phosphoinositide 3-kinase (PI3K) as a point of convergence of cellular signaling pathways that integrates nutrient sensing and inflammatory signaling to regulate tissue insulin sensitivity. |
| 7196 | 23991359 | Adipose tissue insulin sensitivity and macrophage recruitment: Does PI3K pick the pathway? |
| 7197 | 23991359 | In this mini-review, we focus on a potential role of adipose tissue phosphoinositide 3-kinase (PI3K) as a point of convergence of cellular signaling pathways that integrates nutrient sensing and inflammatory signaling to regulate tissue insulin sensitivity. |
| 7198 | 23992308 | Moreover, the protein levels of MMP-2, MMP-9, and VEGF were increased in PC cells transfected with Si-E-cad. |
| 7199 | 23992308 | Finally, the activation of the PI3K/AKT/GSK-3β signaling pathway was demonstrated to be involved in indometacin reversing HG-induced cell proliferation and invasion in PC cells. |
| 7200 | 23994159 | It is believed that the diabetic myocardium is refractory to cardioprotection by ischemic preconditioning (IPC) mainly because of impaired insulin signaling to phosphatidylinositol 3-kinase (PI3K) and protein kinase B (PKB or Akt). |
| 7201 | 23994159 | Therefore, this study was designed to determine whether activation of insulin signaling prior to IPC is detrimental for cardioprotection and to assess the role of insulin receptors (IRs) and Akt in mediating this effect. |
| 7202 | 23994159 | In addition, transgenic induction of Akt in the heart was sufficient to abrogate IPC even when insulin was absent, further confirming the involvement of Akt in insulin's suppression of cardioprotection by IPC. |
| 7203 | 23994159 | These data provide evidence that excessive insulin signaling to Akt is detrimental for cardioprotection by IPC and could explain the failure of the diabetic myocardium to precondition. |
| 7204 | 12975336 | Insulin and glucagon signaling in regulation of microsomal epoxide hydrolase expression in primary cultured rat hepatocytes. |
| 7205 | 12975336 | The phosphatidylinositol 3-kinase (PI3K) inhibitors wortmannin or LY294002 [2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one], and rapamycin, an inhibitor of p70 S6 kinase phosphorylation, ameliorated the insulin-mediated increase in mEH protein levels. |
| 7206 | 12975336 | The p38 mitogen-activated protein (MAP) kinase inhibitors SB203580 and SB202190 also abrogated the insulin-mediated increase in mEH protein. |
| 7207 | 12975336 | Furthermore, these data suggest that PI3K and p70 S6 kinase are active in the regulation of insulin-mediated mEH expression. |
| 7208 | 12975336 | We also provide data implicating p38 MAP kinase in the insulin-mediated increase in mEH levels. |
| 7209 | 12975336 | Insulin and glucagon signaling in regulation of microsomal epoxide hydrolase expression in primary cultured rat hepatocytes. |
| 7210 | 12975336 | The phosphatidylinositol 3-kinase (PI3K) inhibitors wortmannin or LY294002 [2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one], and rapamycin, an inhibitor of p70 S6 kinase phosphorylation, ameliorated the insulin-mediated increase in mEH protein levels. |
| 7211 | 12975336 | The p38 mitogen-activated protein (MAP) kinase inhibitors SB203580 and SB202190 also abrogated the insulin-mediated increase in mEH protein. |
| 7212 | 12975336 | Furthermore, these data suggest that PI3K and p70 S6 kinase are active in the regulation of insulin-mediated mEH expression. |
| 7213 | 12975336 | We also provide data implicating p38 MAP kinase in the insulin-mediated increase in mEH levels. |