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Gene Information
Gene symbol: GSK3B
Gene name: glycogen synthase kinase 3 beta
HGNC ID: 4617
Related Genes
Related Sentences
| # | PMID | Sentence |
| 1 | 9267989 | Activation of glycogen synthesis in skeletal muscle in response to insulin results from the combined inactivation of glycogen synthase kinase-3 (GSK-3) and activation of the protein phosphatase-1, changing the ratio between the inactive phosphorylated state of the glycogen synthase to the active dephosphorylated state. |
| 2 | 9267989 | In a search for genetic defects responsible for the decreased insulin stimulated glycogen synthesis seen in patients with non-insulin-dependent diabetes mellitus (NIDDM) and their glucose-tolerant first-degree relatives we have performed mutational analysis of the coding region of the 2 isoforms of GSK-3alpha and GSK-3beta in 72 NIDDM patients and 12 control subjects. |
| 3 | 9267989 | Mapping of the GSK-3alpha to chromosome 19q13.1-13.2 and the GSK-3beta to chromosome 3q13.3-q21 outside known genetic loci linked to NIDDM further makes it unlikely that these genes are involved in the pathogenesis of common forms of NIDDM. |
| 4 | 9267989 | Activation of glycogen synthesis in skeletal muscle in response to insulin results from the combined inactivation of glycogen synthase kinase-3 (GSK-3) and activation of the protein phosphatase-1, changing the ratio between the inactive phosphorylated state of the glycogen synthase to the active dephosphorylated state. |
| 5 | 9267989 | In a search for genetic defects responsible for the decreased insulin stimulated glycogen synthesis seen in patients with non-insulin-dependent diabetes mellitus (NIDDM) and their glucose-tolerant first-degree relatives we have performed mutational analysis of the coding region of the 2 isoforms of GSK-3alpha and GSK-3beta in 72 NIDDM patients and 12 control subjects. |
| 6 | 9267989 | Mapping of the GSK-3alpha to chromosome 19q13.1-13.2 and the GSK-3beta to chromosome 3q13.3-q21 outside known genetic loci linked to NIDDM further makes it unlikely that these genes are involved in the pathogenesis of common forms of NIDDM. |
| 7 | 10455163 | Part of the mechanism by which insulin stimulates glycogen synthesis may involve phosphorylation and activation of Akt, serine phosphorylation and deactivation of glycogen synthase kinase-3 (GSK-3), leading to dephosphorylation and activation of glycogen synthase. |
| 8 | 10455163 | To study Akt and GSK-3 regulation in muscle, time course experiments on the effects of insulin injection and treadmill running exercise were performed in hindlimb skeletal muscle from male rats. |
| 9 | 10455163 | Insulin stimulation significantly increased Akt phosphorylation and activity, whereas exercise had no effect. |
| 10 | 10455163 | The time course of the insulin-stimulated increase in Akt was closely matched by GSK-3alpha Ser(21) phosphorylation and a 40-60% decrease in GSK-3alpha and GSK-3beta activity. |
| 11 | 10455163 | These data suggest the following: 1) GSK-3 is constitutively active and tyrosine phosphorylated under basal conditions in skeletal muscle, 2) both exercise and insulin are effective regulators of GSK-3 activity in vivo, 3) the insulin-induced deactivation of GSK-3 occurs in response to increased Akt activity and GSK-3 serine phosphorylation, and 4) there is an Akt-independent mechanism for deactivation of GSK-3 in skeletal muscle. |
| 12 | 11272135 | We observed a small but significant increase in GSK3alpha (10-20%) activity in biopsies obtained from vastus lateralis after both low- and high-intensity exercise, whereas GSK3beta activity was unaffected. |
| 13 | 11272135 | Subsequent food intake increased Aktphosphorylation (approximately 2-fold) and deactivated GSK3alpha (approximately 40%), whereas GSK3beta activity was unchanged. |
| 14 | 11272135 | We conclude that GSK3alpha but not GSK3beta may have a role in the regulation of GS activity in response to meal-associated hyperinsulinemia in humans. |
| 15 | 11272135 | We observed a small but significant increase in GSK3alpha (10-20%) activity in biopsies obtained from vastus lateralis after both low- and high-intensity exercise, whereas GSK3beta activity was unaffected. |
| 16 | 11272135 | Subsequent food intake increased Aktphosphorylation (approximately 2-fold) and deactivated GSK3alpha (approximately 40%), whereas GSK3beta activity was unchanged. |
| 17 | 11272135 | We conclude that GSK3alpha but not GSK3beta may have a role in the regulation of GS activity in response to meal-associated hyperinsulinemia in humans. |
| 18 | 11272135 | We observed a small but significant increase in GSK3alpha (10-20%) activity in biopsies obtained from vastus lateralis after both low- and high-intensity exercise, whereas GSK3beta activity was unaffected. |
| 19 | 11272135 | Subsequent food intake increased Aktphosphorylation (approximately 2-fold) and deactivated GSK3alpha (approximately 40%), whereas GSK3beta activity was unchanged. |
| 20 | 11272135 | We conclude that GSK3alpha but not GSK3beta may have a role in the regulation of GS activity in response to meal-associated hyperinsulinemia in humans. |
| 21 | 11334423 | GLUT1 11 +/- 1%, P < 0.0005) as well as Fas-ligand (control 12 +/- 1% vs. |
| 22 | 11334423 | Provocatively, the enhanced glucose metabolism in GLUT1 overexpressing VSMC as well as neointimal tissue correlated with the inactivation of the proapoptotic kinase, glycogen synthase kinase 3beta (GSK3beta). |
| 23 | 11334423 | GSK3beta-induced apoptosis was significantly attenuated by GLUT1 overexpression (GSK3beta 29 +/- 3% vs. |
| 24 | 11334423 | GLUT1 + GSK3beta 6 +/- 1%, n = 12, P < 0.001), suggesting that the antiapoptotic effect of enhanced glucose metabolism is linked to the inactivation of GSK3beta. |
| 25 | 11334423 | GLUT1 11 +/- 1%, P < 0.0005) as well as Fas-ligand (control 12 +/- 1% vs. |
| 26 | 11334423 | Provocatively, the enhanced glucose metabolism in GLUT1 overexpressing VSMC as well as neointimal tissue correlated with the inactivation of the proapoptotic kinase, glycogen synthase kinase 3beta (GSK3beta). |
| 27 | 11334423 | GSK3beta-induced apoptosis was significantly attenuated by GLUT1 overexpression (GSK3beta 29 +/- 3% vs. |
| 28 | 11334423 | GLUT1 + GSK3beta 6 +/- 1%, n = 12, P < 0.001), suggesting that the antiapoptotic effect of enhanced glucose metabolism is linked to the inactivation of GSK3beta. |
| 29 | 11334423 | GLUT1 11 +/- 1%, P < 0.0005) as well as Fas-ligand (control 12 +/- 1% vs. |
| 30 | 11334423 | Provocatively, the enhanced glucose metabolism in GLUT1 overexpressing VSMC as well as neointimal tissue correlated with the inactivation of the proapoptotic kinase, glycogen synthase kinase 3beta (GSK3beta). |
| 31 | 11334423 | GSK3beta-induced apoptosis was significantly attenuated by GLUT1 overexpression (GSK3beta 29 +/- 3% vs. |
| 32 | 11334423 | GLUT1 + GSK3beta 6 +/- 1%, n = 12, P < 0.001), suggesting that the antiapoptotic effect of enhanced glucose metabolism is linked to the inactivation of GSK3beta. |
| 33 | 11809746 | Insulin-stimulated serine phosphorylation of Akt/protein kinase B was significantly impaired in mutant-transfected cells. |
| 34 | 11809746 | Moreover, the ability of insulin to inactivate GS kinase-3beta (GSK-3beta), the regulatory enzyme immediately upstream of GS, by serine phosphorylation (308 +/- 16, 321 +/- 41, and 458 +/- 34 optical densitometric units (odu) in NON, CMV2, and WT, respectively, p < 0.02 for WT versus CMV2) was attenuated in the presence of either FAT (205 +/- 14, p < 0.01) or KR (189 +/- 4, p < 0.005) mutants. |
| 35 | 11809746 | FAK co-immunoprecipitated with GSK-3beta, but only in cells overexpressing the KR (374 +/- 254 odu) and FAT (555 +/- 308) mutants was this association stimulated by insulin compared with NON (-209 +/- 92), CMV2 (-47 +/- 70), and WT (-39 +/- 31 odu). |
| 36 | 11809746 | This suggests that FAK and GSK-3beta form both a constitutive association and a transient complex upon insulin stimulation, the dissociation of which requires normal function and localization of FAK. |
| 37 | 11809746 | We conclude that FAK regulates the activity of Akt/protein kinase B and GSK-3beta and the association of GSK-3beta with FAK to influence insulin-stimulated glycogen synthesis in hepatocytes. |
| 38 | 11809746 | Insulin-stimulated serine phosphorylation of Akt/protein kinase B was significantly impaired in mutant-transfected cells. |
| 39 | 11809746 | Moreover, the ability of insulin to inactivate GS kinase-3beta (GSK-3beta), the regulatory enzyme immediately upstream of GS, by serine phosphorylation (308 +/- 16, 321 +/- 41, and 458 +/- 34 optical densitometric units (odu) in NON, CMV2, and WT, respectively, p < 0.02 for WT versus CMV2) was attenuated in the presence of either FAT (205 +/- 14, p < 0.01) or KR (189 +/- 4, p < 0.005) mutants. |
| 40 | 11809746 | FAK co-immunoprecipitated with GSK-3beta, but only in cells overexpressing the KR (374 +/- 254 odu) and FAT (555 +/- 308) mutants was this association stimulated by insulin compared with NON (-209 +/- 92), CMV2 (-47 +/- 70), and WT (-39 +/- 31 odu). |
| 41 | 11809746 | This suggests that FAK and GSK-3beta form both a constitutive association and a transient complex upon insulin stimulation, the dissociation of which requires normal function and localization of FAK. |
| 42 | 11809746 | We conclude that FAK regulates the activity of Akt/protein kinase B and GSK-3beta and the association of GSK-3beta with FAK to influence insulin-stimulated glycogen synthesis in hepatocytes. |
| 43 | 11809746 | Insulin-stimulated serine phosphorylation of Akt/protein kinase B was significantly impaired in mutant-transfected cells. |
| 44 | 11809746 | Moreover, the ability of insulin to inactivate GS kinase-3beta (GSK-3beta), the regulatory enzyme immediately upstream of GS, by serine phosphorylation (308 +/- 16, 321 +/- 41, and 458 +/- 34 optical densitometric units (odu) in NON, CMV2, and WT, respectively, p < 0.02 for WT versus CMV2) was attenuated in the presence of either FAT (205 +/- 14, p < 0.01) or KR (189 +/- 4, p < 0.005) mutants. |
| 45 | 11809746 | FAK co-immunoprecipitated with GSK-3beta, but only in cells overexpressing the KR (374 +/- 254 odu) and FAT (555 +/- 308) mutants was this association stimulated by insulin compared with NON (-209 +/- 92), CMV2 (-47 +/- 70), and WT (-39 +/- 31 odu). |
| 46 | 11809746 | This suggests that FAK and GSK-3beta form both a constitutive association and a transient complex upon insulin stimulation, the dissociation of which requires normal function and localization of FAK. |
| 47 | 11809746 | We conclude that FAK regulates the activity of Akt/protein kinase B and GSK-3beta and the association of GSK-3beta with FAK to influence insulin-stimulated glycogen synthesis in hepatocytes. |
| 48 | 11809746 | Insulin-stimulated serine phosphorylation of Akt/protein kinase B was significantly impaired in mutant-transfected cells. |
| 49 | 11809746 | Moreover, the ability of insulin to inactivate GS kinase-3beta (GSK-3beta), the regulatory enzyme immediately upstream of GS, by serine phosphorylation (308 +/- 16, 321 +/- 41, and 458 +/- 34 optical densitometric units (odu) in NON, CMV2, and WT, respectively, p < 0.02 for WT versus CMV2) was attenuated in the presence of either FAT (205 +/- 14, p < 0.01) or KR (189 +/- 4, p < 0.005) mutants. |
| 50 | 11809746 | FAK co-immunoprecipitated with GSK-3beta, but only in cells overexpressing the KR (374 +/- 254 odu) and FAT (555 +/- 308) mutants was this association stimulated by insulin compared with NON (-209 +/- 92), CMV2 (-47 +/- 70), and WT (-39 +/- 31 odu). |
| 51 | 11809746 | This suggests that FAK and GSK-3beta form both a constitutive association and a transient complex upon insulin stimulation, the dissociation of which requires normal function and localization of FAK. |
| 52 | 11809746 | We conclude that FAK regulates the activity of Akt/protein kinase B and GSK-3beta and the association of GSK-3beta with FAK to influence insulin-stimulated glycogen synthesis in hepatocytes. |
| 53 | 11952162 | In vivo effects of insulin and vanadium treatment on glycogen synthase (GS), glycogen synthase kinase-3 (GSK-3) and protein phosphatase-1 (PP1) activity were determined in Wistar rats with streptozotocin (STZ)-induced diabetes. |
| 54 | 11952162 | Diabetes, vanadium, and insulin in vivo treatment did not affect muscle GSK-3beta activity as compared to controls. |
| 55 | 11959983 | Elevated nucleocytoplasmic glycosylation by O-GlcNAc results in insulin resistance associated with defects in Akt activation in 3T3-L1 adipocytes. |
| 56 | 11959983 | Cycling of the O-GlcNAc posttranslational modification was blocked by pharmacological inhibition of O-GlcNAcase, the enzyme that catalyzes O-GlcNAc removal from proteins, with O-(2-acetamido-2-deoxy-d-glucopyranosylidene)amino-N-phenylcarbamate (PUGNAc). |
| 57 | 11959983 | PUGNAc treatment increased levels of O-GlcNAc and caused insulin resistance in 3T3-L1 adipocytes. |
| 58 | 11959983 | Insulin resistance induced through the HSP by glucosamine and chronic insulin treatment correlated with increased O-GlcNAc levels on nucleocytoplasmic proteins. |
| 59 | 11959983 | Whereas insulin receptor autophosphorylation and insulin receptor substrate 2 tyrosine phosphorylation were not affected by PUGNAc inhibition of O-GlcNAcase, downstream phosphorylation of Akt at Thr-308 and glycogen synthase kinase 3 beta at Ser-9 was inhibited. |
| 60 | 11959983 | PUGNAc-induced insulin resistance was associated with increased O-GlcNAc modification of several proteins including insulin receptor substrate 1 and beta-catenin, two important effectors of insulin signaling. |
| 61 | 11959983 | These results suggest that elevation of O-GlcNAc levels attenuate insulin signaling and contribute to the mechanism by which increased flux through the HSP leads to insulin resistance in adipocytes. |
| 62 | 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. |
| 63 | 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. |
| 64 | 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. |
| 65 | 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. |
| 66 | 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. |
| 67 | 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. |
| 68 | 12083774 | The insulin-like effect of zinc cations raises the possibility that they inhibit glycogen synthase kinase-3beta (GSK-3beta), a serine/threonine protein kinase linked with insulin resistance and type 2 diabetes. |
| 69 | 12083774 | Treatment of HEK-293 cells with zinc enhanced glycogen synthase activity and increased the intracellular levels of beta-catenin, providing evidence for inhibition of endogenous GSK-3beta by zinc. |
| 70 | 12083774 | We propose that the in vivo insulin-mimetic actions of zinc are mediated via direct inhibition of endogenous GSK-3beta. |
| 71 | 12083774 | The insulin-like effect of zinc cations raises the possibility that they inhibit glycogen synthase kinase-3beta (GSK-3beta), a serine/threonine protein kinase linked with insulin resistance and type 2 diabetes. |
| 72 | 12083774 | Treatment of HEK-293 cells with zinc enhanced glycogen synthase activity and increased the intracellular levels of beta-catenin, providing evidence for inhibition of endogenous GSK-3beta by zinc. |
| 73 | 12083774 | We propose that the in vivo insulin-mimetic actions of zinc are mediated via direct inhibition of endogenous GSK-3beta. |
| 74 | 12083774 | The insulin-like effect of zinc cations raises the possibility that they inhibit glycogen synthase kinase-3beta (GSK-3beta), a serine/threonine protein kinase linked with insulin resistance and type 2 diabetes. |
| 75 | 12083774 | Treatment of HEK-293 cells with zinc enhanced glycogen synthase activity and increased the intracellular levels of beta-catenin, providing evidence for inhibition of endogenous GSK-3beta by zinc. |
| 76 | 12083774 | We propose that the in vivo insulin-mimetic actions of zinc are mediated via direct inhibition of endogenous GSK-3beta. |
| 77 | 12095990 | Fatty acid infusion selectively impairs insulin action on Akt1 and protein kinase C lambda /zeta but not on glycogen synthase kinase-3. |
| 78 | 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. |
| 79 | 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. |
| 80 | 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. |
| 81 | 12095990 | Insulin increased Akt1 activity 3.9-fold in glycerol-infused rats, and this was impaired 41% in lipid-infused rats. |
| 82 | 12095990 | Insulin action on Akt2 and p70S6K were not impaired, whereas activation of protein kinase C lambda/zeta activity was reduced 47%. |
| 83 | 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. |
| 84 | 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. |
| 85 | 12111750 | Two forms of the enzyme, GSK-3alpha and GSK-3beta, have been previously identified. |
| 86 | 12421827 | Transcriptional activation of the proglucagon gene by lithium and beta-catenin in intestinal endocrine L cells. |
| 87 | 12421827 | Although proglucagon transcription and GLP-1 synthesis were shown to be activated by forskolin and other protein kinase A (PKA) activators, deleting or mutating the cAMP-response element (CRE) only moderately attenuates the proglucagon gene promoter in response to PKA activation. |
| 88 | 12421827 | We show here that lithium, an inhibitor of GSK-3beta, activates proglucagon gene transcription and stimulates GLP-1 synthesis in an intestinal endocrine L cell line, GLUTag. |
| 89 | 12421827 | Co-transfection of beta-catenin, a downstream effector of GSK-3beta activities, activated the proglucagon gene promoter without a CRE. |
| 90 | 12421827 | Furthermore, forskolin and 8-Br-cAMP phosphorylated GSK-3beta at serine 9 in intestinal proglucagon-producing cells, and both lithium and forskolin induced the accumulation of free beta-catenin in these cell lines. |
| 91 | 12421827 | Transcriptional activation of the proglucagon gene by lithium and beta-catenin in intestinal endocrine L cells. |
| 92 | 12421827 | Although proglucagon transcription and GLP-1 synthesis were shown to be activated by forskolin and other protein kinase A (PKA) activators, deleting or mutating the cAMP-response element (CRE) only moderately attenuates the proglucagon gene promoter in response to PKA activation. |
| 93 | 12421827 | We show here that lithium, an inhibitor of GSK-3beta, activates proglucagon gene transcription and stimulates GLP-1 synthesis in an intestinal endocrine L cell line, GLUTag. |
| 94 | 12421827 | Co-transfection of beta-catenin, a downstream effector of GSK-3beta activities, activated the proglucagon gene promoter without a CRE. |
| 95 | 12421827 | Furthermore, forskolin and 8-Br-cAMP phosphorylated GSK-3beta at serine 9 in intestinal proglucagon-producing cells, and both lithium and forskolin induced the accumulation of free beta-catenin in these cell lines. |
| 96 | 12421827 | Transcriptional activation of the proglucagon gene by lithium and beta-catenin in intestinal endocrine L cells. |
| 97 | 12421827 | Although proglucagon transcription and GLP-1 synthesis were shown to be activated by forskolin and other protein kinase A (PKA) activators, deleting or mutating the cAMP-response element (CRE) only moderately attenuates the proglucagon gene promoter in response to PKA activation. |
| 98 | 12421827 | We show here that lithium, an inhibitor of GSK-3beta, activates proglucagon gene transcription and stimulates GLP-1 synthesis in an intestinal endocrine L cell line, GLUTag. |
| 99 | 12421827 | Co-transfection of beta-catenin, a downstream effector of GSK-3beta activities, activated the proglucagon gene promoter without a CRE. |
| 100 | 12421827 | Furthermore, forskolin and 8-Br-cAMP phosphorylated GSK-3beta at serine 9 in intestinal proglucagon-producing cells, and both lithium and forskolin induced the accumulation of free beta-catenin in these cell lines. |
| 101 | 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. |
| 102 | 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. |
| 103 | 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. |
| 104 | 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. |
| 105 | 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. |
| 106 | 12540292 | Recent evidence suggests that glycogen-associated protein phosphatase 1 (PP-1(G)) is essential for basal and exercise-induced glycogen synthesis, which is mediated in part by dephosphorylation and activation of glycogen synthase (GS). |
| 107 | 12540292 | Heat shock also resulted in a rapid and sustained Akt/ glycogen synthase kinase 3 beta (GSK-3 beta) phosphorylation. |
| 108 | 12684506 | L-PGDS (50 microg/ml) was able to significantly inhibit VSMC proliferation and DNA synthesis and induce the apoptotic genes bax, bcl-x, and ei24 in SHR but had no effect on WKY cells. |
| 109 | 12684506 | Furthermore, we examined the effect of L-PGDS incubation on insulin-stimulated Akt, glycogen synthase kinase-3beta (GSK-3beta), and ERK phosphorylation. |
| 110 | 12684506 | Unexpectedly, we found that when WKY cells were pretreated with L-PGDS, insulin could actually induce apoptosis and failed to stimulate Akt/GSK-3beta phosphorylation. |
| 111 | 12684506 | Insulin-stimulated ERK phosphorylation was unaffected by L-PGDS pretreatment in both cell lines. |
| 112 | 12684506 | L-PGDS (50 microg/ml) was able to significantly inhibit VSMC proliferation and DNA synthesis and induce the apoptotic genes bax, bcl-x, and ei24 in SHR but had no effect on WKY cells. |
| 113 | 12684506 | Furthermore, we examined the effect of L-PGDS incubation on insulin-stimulated Akt, glycogen synthase kinase-3beta (GSK-3beta), and ERK phosphorylation. |
| 114 | 12684506 | Unexpectedly, we found that when WKY cells were pretreated with L-PGDS, insulin could actually induce apoptosis and failed to stimulate Akt/GSK-3beta phosphorylation. |
| 115 | 12684506 | Insulin-stimulated ERK phosphorylation was unaffected by L-PGDS pretreatment in both cell lines. |
| 116 | 12711303 | Among the subtypes, DCAPL3 shows significant homology with CAP, an essential component of glucose transport in insulin signal. |
| 117 | 12711303 | Further binding assay revealed that DCAP binds to not only Axin but also Arrow, and Axin binds to not only GSK3beta but also Arrow. |
| 118 | 12711303 | Moreover, early stage embryos lacking maternal Axin show significant delay of initial glycogen decomposition, and RNAi of Axin in S2 cells revealed quite increase of endogenous glycogen level as well as GSK3beta. |
| 119 | 12711303 | In addition, the interaction among Axin, Arrow, and DCAP implies a possible cross-talk between Wnt signal and insulin signal. |
| 120 | 12711303 | Among the subtypes, DCAPL3 shows significant homology with CAP, an essential component of glucose transport in insulin signal. |
| 121 | 12711303 | Further binding assay revealed that DCAP binds to not only Axin but also Arrow, and Axin binds to not only GSK3beta but also Arrow. |
| 122 | 12711303 | Moreover, early stage embryos lacking maternal Axin show significant delay of initial glycogen decomposition, and RNAi of Axin in S2 cells revealed quite increase of endogenous glycogen level as well as GSK3beta. |
| 123 | 12711303 | In addition, the interaction among Axin, Arrow, and DCAP implies a possible cross-talk between Wnt signal and insulin signal. |
| 124 | 14747284 | Leptin impairs insulin signaling in rat adipocytes. |
| 125 | 14747284 | Leptin modulates glucose homeostasis by acting as an insulin-sensitizing factor in most insulin target tissues. |
| 126 | 14747284 | Moreover, elevated leptin concentrations inhibit insulin metabolic effects in adipocytes. |
| 127 | 14747284 | Here we studied both, direct and centrally mediated effects of leptin on insulin signaling in rat adipocytes. |
| 128 | 14747284 | Adipocyte incubation with low leptin concentrations did not modify the insulin stimulation of mitogen-activated protein kinase (MAPK). |
| 129 | 14747284 | However, at elevated concentrations, leptin impaired insulin-stimulated MAPK activity, glycogen synthase kinase (GSK)3beta phosphorylation, and insulin receptor tyrosine phosphorylation without altering vanadate stimulation. |
| 130 | 14747284 | Central administration of leptin decreased insulin effects on adipocyte MAPK and GSK3beta phosphorylation. |
| 131 | 14747284 | In insulin-resistant aged rats with hyperleptinemia and central leptin resistance, insulin poorly stimulated MAPK and central leptin infusion did not further deteriorate adipocyte insulin responsiveness. |
| 132 | 14747284 | Food restriction increased MAPK stimulation by insulin and restored the ability of centrally infused leptin to attenuate adipocyte insulin signaling in aged rats. |
| 133 | 14747284 | We conclude that leptin can modulate, in an inhibitory manner, adipocyte insulin signaling by two different ways: as an autocrine signal and, indirectly, through neuroendocrine pathways. |
| 134 | 15084270 | Coligation of Notch 1 together with TCR and CD28 resulted in a dramatic inhibition of T cell activation, proliferation, and cytokine production. |
| 135 | 15084270 | This effect was dependent on presenilin activity and induced the expression of HES-1, suggestive of Notch 1 signaling. |
| 136 | 15084270 | Biochemical analysis demonstrated an inhibition of AKT and GSK3beta phosphorylation following Notch 1 engagement while other biochemical signals such as TCR and ERK phosphorylation remained intact. |
| 137 | 15094374 | The expression of Wnt signaling genes, WNT1, FZD1, DVL1, GSK3beta, beta-catenin, and TCF1, and adipogenic transcription factors, C/EBPalpha and beta and delta, PPARgamma, and SREBP-1, was reduced in the adipose tissue. |
| 138 | 15094374 | The expression of adipose-specific proteins related to terminal differentiation, such as adiponectin and aP2, was reduced both in the adipose tissue and in the adipose cells isolated from portions of the biopsies. |
| 139 | 15094374 | The adipose cells were enlarged in the insulin-resistant relatives and the cell size inversely correlated with the expression of the Wnt signaling genes, adiponectin, and aP2. |
| 140 | 15194499 | In myotubes established from type 2 diabetic and healthy control subjects we determined GS activity ratio, protein expression, and activity of GSK-3alpha and beta under basal and insulin-stimulated conditions when precultured in increasing insulin concentrations. |
| 141 | 15194499 | In myotubes precultured at low insulin concentrations acute insulin stimulation increased GS activity more in control than in diabetic subjects, whereas the corresponding GSK-3alpha but not GSK-3beta activity was significantly reduced by acute insulin treatment in both groups. |
| 142 | 15194499 | However, in myotubes precultured at high insulin concentrations the effect of insulin on GS and GSK-3alpha activity was blunted in both groups. |
| 143 | 15194499 | In conclusion, myotubes with a primary defect in GS activity express insulin responsive GSK-3alpha, suggesting that failure of insulin to decrease GS phosphorylation involves abnormal activity of another kinase or phosphatase. |
| 144 | 15375789 | The male GSK-3beta transgenic mice had significantly raised plasma insulin levels and by 24 weeks of age became glucose-intolerant as determined by a 50% increase in the area under their oral glucose tolerance curve (P < .001). |
| 145 | 15375789 | At 29 weeks of age, GSK-3beta protein levels were 5-fold higher, and glycogen synthase activation (-27%), glycogen levels (-58%) and insulin receptor substrate-1 (IRS-1) protein levels (-67%) were significantly reduced in skeletal muscle. |
| 146 | 15375789 | We conclude that overexpression of human GSK-3beta in skeletal muscle of male mice resulted in impaired glucose tolerance despite raised insulin levels, consistent with the possibility that elevated levels of GSK-3 in type 2 diabetes are partly responsible for insulin resistance. |
| 147 | 15375789 | The male GSK-3beta transgenic mice had significantly raised plasma insulin levels and by 24 weeks of age became glucose-intolerant as determined by a 50% increase in the area under their oral glucose tolerance curve (P < .001). |
| 148 | 15375789 | At 29 weeks of age, GSK-3beta protein levels were 5-fold higher, and glycogen synthase activation (-27%), glycogen levels (-58%) and insulin receptor substrate-1 (IRS-1) protein levels (-67%) were significantly reduced in skeletal muscle. |
| 149 | 15375789 | We conclude that overexpression of human GSK-3beta in skeletal muscle of male mice resulted in impaired glucose tolerance despite raised insulin levels, consistent with the possibility that elevated levels of GSK-3 in type 2 diabetes are partly responsible for insulin resistance. |
| 150 | 15375789 | The male GSK-3beta transgenic mice had significantly raised plasma insulin levels and by 24 weeks of age became glucose-intolerant as determined by a 50% increase in the area under their oral glucose tolerance curve (P < .001). |
| 151 | 15375789 | At 29 weeks of age, GSK-3beta protein levels were 5-fold higher, and glycogen synthase activation (-27%), glycogen levels (-58%) and insulin receptor substrate-1 (IRS-1) protein levels (-67%) were significantly reduced in skeletal muscle. |
| 152 | 15375789 | We conclude that overexpression of human GSK-3beta in skeletal muscle of male mice resulted in impaired glucose tolerance despite raised insulin levels, consistent with the possibility that elevated levels of GSK-3 in type 2 diabetes are partly responsible for insulin resistance. |
| 153 | 15507471 | The proinvasive activity of Wnt-2 is mediated through a noncanonical Wnt pathway coupled to GSK-3beta and c-Jun/AP-1 signaling. |
| 154 | 15507471 | Here, we show that two activators of the canonical Wnt/beta-catenin transcription pathway, namely Dvl-2, the Axin 501-560 fragment binding glycogen synthase kinase -3beta (GSK-3beta), and the negative Wnt regulator wt-Axin did not alter cell invasion into type I collagen. |
| 155 | 15507471 | In addition, both Dvl-2 and Axin 501-560 exerted a permissive action on the proinvasive activity of HGF and intestinal trefoil factor. |
| 156 | 15507471 | Upstream activation of Wnt signaling by the Wnt-2 and Wnt-3a ligands, stable overexpression of Wnt-2, as well as GSK-3beta inhibition by lithium, SB216763, and GSK-3beta dominant negative forms (K85R and R96E) conferred the invasive phenotype through several proinvasive pathways. |
| 157 | 15507471 | Induction of the matrix metalloprotease MMP-7 (matrilysin) gene and protein by Wnt-2 was abolished by inactivation of the AP-1 binding site in the promoter. |
| 158 | 15507471 | Accordingly, invasion induced by Wnt-2 was prevented by soluble FRP-3 and FRP-1, sequestration of Gbetagamma subunits, depletion of the GSK-3beta protein by RNA interference, the c-Jun dominant negative mutant TAM67 and was not reversed by wt-Axin. |
| 159 | 15507471 | Thus, the proinvasive activity of Wnt-2 is mediated by a noncanonical Wnt pathway using GSK-3beta and the AP-1 oncogene. |
| 160 | 15507471 | The proinvasive activity of Wnt-2 is mediated through a noncanonical Wnt pathway coupled to GSK-3beta and c-Jun/AP-1 signaling. |
| 161 | 15507471 | Here, we show that two activators of the canonical Wnt/beta-catenin transcription pathway, namely Dvl-2, the Axin 501-560 fragment binding glycogen synthase kinase -3beta (GSK-3beta), and the negative Wnt regulator wt-Axin did not alter cell invasion into type I collagen. |
| 162 | 15507471 | In addition, both Dvl-2 and Axin 501-560 exerted a permissive action on the proinvasive activity of HGF and intestinal trefoil factor. |
| 163 | 15507471 | Upstream activation of Wnt signaling by the Wnt-2 and Wnt-3a ligands, stable overexpression of Wnt-2, as well as GSK-3beta inhibition by lithium, SB216763, and GSK-3beta dominant negative forms (K85R and R96E) conferred the invasive phenotype through several proinvasive pathways. |
| 164 | 15507471 | Induction of the matrix metalloprotease MMP-7 (matrilysin) gene and protein by Wnt-2 was abolished by inactivation of the AP-1 binding site in the promoter. |
| 165 | 15507471 | Accordingly, invasion induced by Wnt-2 was prevented by soluble FRP-3 and FRP-1, sequestration of Gbetagamma subunits, depletion of the GSK-3beta protein by RNA interference, the c-Jun dominant negative mutant TAM67 and was not reversed by wt-Axin. |
| 166 | 15507471 | Thus, the proinvasive activity of Wnt-2 is mediated by a noncanonical Wnt pathway using GSK-3beta and the AP-1 oncogene. |
| 167 | 15507471 | The proinvasive activity of Wnt-2 is mediated through a noncanonical Wnt pathway coupled to GSK-3beta and c-Jun/AP-1 signaling. |
| 168 | 15507471 | Here, we show that two activators of the canonical Wnt/beta-catenin transcription pathway, namely Dvl-2, the Axin 501-560 fragment binding glycogen synthase kinase -3beta (GSK-3beta), and the negative Wnt regulator wt-Axin did not alter cell invasion into type I collagen. |
| 169 | 15507471 | In addition, both Dvl-2 and Axin 501-560 exerted a permissive action on the proinvasive activity of HGF and intestinal trefoil factor. |
| 170 | 15507471 | Upstream activation of Wnt signaling by the Wnt-2 and Wnt-3a ligands, stable overexpression of Wnt-2, as well as GSK-3beta inhibition by lithium, SB216763, and GSK-3beta dominant negative forms (K85R and R96E) conferred the invasive phenotype through several proinvasive pathways. |
| 171 | 15507471 | Induction of the matrix metalloprotease MMP-7 (matrilysin) gene and protein by Wnt-2 was abolished by inactivation of the AP-1 binding site in the promoter. |
| 172 | 15507471 | Accordingly, invasion induced by Wnt-2 was prevented by soluble FRP-3 and FRP-1, sequestration of Gbetagamma subunits, depletion of the GSK-3beta protein by RNA interference, the c-Jun dominant negative mutant TAM67 and was not reversed by wt-Axin. |
| 173 | 15507471 | Thus, the proinvasive activity of Wnt-2 is mediated by a noncanonical Wnt pathway using GSK-3beta and the AP-1 oncogene. |
| 174 | 15507471 | The proinvasive activity of Wnt-2 is mediated through a noncanonical Wnt pathway coupled to GSK-3beta and c-Jun/AP-1 signaling. |
| 175 | 15507471 | Here, we show that two activators of the canonical Wnt/beta-catenin transcription pathway, namely Dvl-2, the Axin 501-560 fragment binding glycogen synthase kinase -3beta (GSK-3beta), and the negative Wnt regulator wt-Axin did not alter cell invasion into type I collagen. |
| 176 | 15507471 | In addition, both Dvl-2 and Axin 501-560 exerted a permissive action on the proinvasive activity of HGF and intestinal trefoil factor. |
| 177 | 15507471 | Upstream activation of Wnt signaling by the Wnt-2 and Wnt-3a ligands, stable overexpression of Wnt-2, as well as GSK-3beta inhibition by lithium, SB216763, and GSK-3beta dominant negative forms (K85R and R96E) conferred the invasive phenotype through several proinvasive pathways. |
| 178 | 15507471 | Induction of the matrix metalloprotease MMP-7 (matrilysin) gene and protein by Wnt-2 was abolished by inactivation of the AP-1 binding site in the promoter. |
| 179 | 15507471 | Accordingly, invasion induced by Wnt-2 was prevented by soluble FRP-3 and FRP-1, sequestration of Gbetagamma subunits, depletion of the GSK-3beta protein by RNA interference, the c-Jun dominant negative mutant TAM67 and was not reversed by wt-Axin. |
| 180 | 15507471 | Thus, the proinvasive activity of Wnt-2 is mediated by a noncanonical Wnt pathway using GSK-3beta and the AP-1 oncogene. |
| 181 | 15507471 | The proinvasive activity of Wnt-2 is mediated through a noncanonical Wnt pathway coupled to GSK-3beta and c-Jun/AP-1 signaling. |
| 182 | 15507471 | Here, we show that two activators of the canonical Wnt/beta-catenin transcription pathway, namely Dvl-2, the Axin 501-560 fragment binding glycogen synthase kinase -3beta (GSK-3beta), and the negative Wnt regulator wt-Axin did not alter cell invasion into type I collagen. |
| 183 | 15507471 | In addition, both Dvl-2 and Axin 501-560 exerted a permissive action on the proinvasive activity of HGF and intestinal trefoil factor. |
| 184 | 15507471 | Upstream activation of Wnt signaling by the Wnt-2 and Wnt-3a ligands, stable overexpression of Wnt-2, as well as GSK-3beta inhibition by lithium, SB216763, and GSK-3beta dominant negative forms (K85R and R96E) conferred the invasive phenotype through several proinvasive pathways. |
| 185 | 15507471 | Induction of the matrix metalloprotease MMP-7 (matrilysin) gene and protein by Wnt-2 was abolished by inactivation of the AP-1 binding site in the promoter. |
| 186 | 15507471 | Accordingly, invasion induced by Wnt-2 was prevented by soluble FRP-3 and FRP-1, sequestration of Gbetagamma subunits, depletion of the GSK-3beta protein by RNA interference, the c-Jun dominant negative mutant TAM67 and was not reversed by wt-Axin. |
| 187 | 15507471 | Thus, the proinvasive activity of Wnt-2 is mediated by a noncanonical Wnt pathway using GSK-3beta and the AP-1 oncogene. |
| 188 | 15559249 | Three closely related forms of glycogen synthase kinase 3 (GSK-3alpha, GSK-3beta and GSK-3beta2) have a major role in Wnt and Hedgehog signaling pathways and regulate the cell-division cycle, stem-cell renewal and differentiation, apoptosis, circadian rhythm, transcription and insulin action. |
| 189 | 15559249 | GSK-3, as part of a multi-protein complex that contains proteins such as axin, presenilin and beta-catenin, contains many additional target sites for specific modulation of its activity. |
| 190 | 15585669 | In vitro studies indicate that lithium can induce renal medullary interstitial cell cyclooxygenase 2 (COX2) protein expression via inhibition of glycogen synthase kinase-3beta (GSK-3beta). |
| 191 | 15585669 | Both COX1 and COX2 are expressed in the kidney. |
| 192 | 15585669 | The present studies examined whether induction of the COX2 isoform contributes to LiCl-induced polyuria. |
| 193 | 15585669 | This was temporally associated with increased renal COX2 protein expression and increased urinary PGE(2) excretion, whereas COX1 levels remained unchanged. |
| 194 | 15585669 | COX2 inhibition significantly blunted lithium-induced polyuria (P < 0.0001) and reduced urinary PGE(2) levels. |
| 195 | 15585669 | COX2 inhibition completely prevented polyuria and PGE(2) excretion in COX1-/- mice, suggesting that COX2, but not COX1, plays a critical role in lithium-induced polyuria. |
| 196 | 15585669 | Lithium also induced renal medullary COX2 protein expression in congenitally polyuric antidiuretic hormone (AHD)-deficient rats, demonstrating that lithium-induced COX2 protein expression is not secondary to altered ADH levels or polyuria. |
| 197 | 15585669 | Lithium also decreased renal medullary GSK-3beta activity, and this was temporally related to increased COX2 expression in the kidney from lithium-treated mice, consistent with a tonic in vivo suppression of COX2 expression by GSK-3 activity. |
| 198 | 15585669 | In conclusion, these findings temporally link decreased GSK-3 activity to enhanced renal COX2 expression and COX2-derived urine PGE(2) excretion. |
| 199 | 15585669 | In vitro studies indicate that lithium can induce renal medullary interstitial cell cyclooxygenase 2 (COX2) protein expression via inhibition of glycogen synthase kinase-3beta (GSK-3beta). |
| 200 | 15585669 | Both COX1 and COX2 are expressed in the kidney. |
| 201 | 15585669 | The present studies examined whether induction of the COX2 isoform contributes to LiCl-induced polyuria. |
| 202 | 15585669 | This was temporally associated with increased renal COX2 protein expression and increased urinary PGE(2) excretion, whereas COX1 levels remained unchanged. |
| 203 | 15585669 | COX2 inhibition significantly blunted lithium-induced polyuria (P < 0.0001) and reduced urinary PGE(2) levels. |
| 204 | 15585669 | COX2 inhibition completely prevented polyuria and PGE(2) excretion in COX1-/- mice, suggesting that COX2, but not COX1, plays a critical role in lithium-induced polyuria. |
| 205 | 15585669 | Lithium also induced renal medullary COX2 protein expression in congenitally polyuric antidiuretic hormone (AHD)-deficient rats, demonstrating that lithium-induced COX2 protein expression is not secondary to altered ADH levels or polyuria. |
| 206 | 15585669 | Lithium also decreased renal medullary GSK-3beta activity, and this was temporally related to increased COX2 expression in the kidney from lithium-treated mice, consistent with a tonic in vivo suppression of COX2 expression by GSK-3 activity. |
| 207 | 15585669 | In conclusion, these findings temporally link decreased GSK-3 activity to enhanced renal COX2 expression and COX2-derived urine PGE(2) excretion. |
| 208 | 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). |
| 209 | 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. |
| 210 | 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%). |
| 211 | 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). |
| 212 | 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. |
| 213 | 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%). |
| 214 | 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. |
| 215 | 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. |
| 216 | 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). |
| 217 | 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. |
| 218 | 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. |
| 219 | 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. |
| 220 | 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). |
| 221 | 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. |
| 222 | 15855348 | Cardiac function was significantly improved after kallikrein gene transfer as evidenced by increased cardiac output and +/-delta P/delta t (maximum speed of contraction/relaxation), along with elevated cardiac sarco(endo)plasmic reticulum (Ca2+ + Mg2+)-ATPase (SERCA)-2a, phosphorylated phospholamban, NOx and cAMP levels, and GLUT4 translocation into plasma membranes of cardiac and skeletal muscle. |
| 223 | 15855348 | Kallikrein gene delivery also increased Akt and glycogen synthase kinase (GSK)-3beta phosphorylation, resulting in decreased GSK-3beta activity in the heart. |
| 224 | 16039605 | The effect of insulin deficiency on tau and neurofilament in the insulin knockout mouse. |
| 225 | 16039605 | In addition, we showed hyperphosphorylation of c-Jun N-terminal kinase (JNK) and glycogen synthase kinase 3 beta (GSK-3 beta) at serine 9. |
| 226 | 16039605 | Extracellular signal-regulated kinase 1 (ERK 1) showed decrease in phosphorylation, whereas ERK 2 showed no changes. |
| 227 | 16039605 | Thus, lack of insulin brain stimulation induces JNK hyperphosphorylation followed by hyperphosphorylation of tau and neurofilament, and ultrastructural cellular damage, that over time may induce decrease in cognition and learning disabilities. |
| 228 | 16055077 | Since inorganic vanadium compounds have been found to activate several key components of the insulin signaling cascade, such as protein kinase B (PKB), the objective of the present study was to investigate if stimulation of PKB and its downstream target glycogen synthase kinase-3 (GSK-3), are responsible for the more potent insulinomimetic effects of OVC. |
| 229 | 16055077 | Among several vanadium compounds tested, vanadium (IV) oxo bis (acetylacetonate) and vanadium (IV) oxo bis(maltolato) markedly induced the phosphorylation of PKB as well as GSK-3beta compared to vanadyl sulfate (VS), an inorganic vanadium salts in Chinese hamster ovary cells overexpressing the insulin receptor (IR). |
| 230 | 16055077 | In addition, greater IRS-1/p85alpha interaction was elicited by the OVC than by VS. |
| 231 | 16055077 | These data indicate that the higher PTPase inhibitory potential of OVC translates into greater phosphorylation of PKB and GSK-3beta, which, in turn, may contribute to a more potent effect of OVC on glucose homeostasis. |
| 232 | 16055077 | Since inorganic vanadium compounds have been found to activate several key components of the insulin signaling cascade, such as protein kinase B (PKB), the objective of the present study was to investigate if stimulation of PKB and its downstream target glycogen synthase kinase-3 (GSK-3), are responsible for the more potent insulinomimetic effects of OVC. |
| 233 | 16055077 | Among several vanadium compounds tested, vanadium (IV) oxo bis (acetylacetonate) and vanadium (IV) oxo bis(maltolato) markedly induced the phosphorylation of PKB as well as GSK-3beta compared to vanadyl sulfate (VS), an inorganic vanadium salts in Chinese hamster ovary cells overexpressing the insulin receptor (IR). |
| 234 | 16055077 | In addition, greater IRS-1/p85alpha interaction was elicited by the OVC than by VS. |
| 235 | 16055077 | These data indicate that the higher PTPase inhibitory potential of OVC translates into greater phosphorylation of PKB and GSK-3beta, which, in turn, may contribute to a more potent effect of OVC on glucose homeostasis. |
| 236 | 16135669 | Inhibition of PI-3 kinase/Akt/mTOR, but not calcineurin signaling, reverses insulin-like growth factor I-induced protection against glucose toxicity in cardiomyocyte contractile function. |
| 237 | 16135669 | Insulin-like growth factor-I (IGF-1) ameliorates cardiac dysfunction in diabetes although the mechanism of action remains poorly understood. |
| 238 | 16135669 | This study examined the role of PI-3 kinase/Akt/mammalian target of rapamycin (mTOR) and calcineurin pathways in cardiac effects of IGF-1 against glucose toxicity. |
| 239 | 16135669 | Adult rat ventricular myocytes were cultured for 8 h with either normal (NG, 5.5 mM) or high (HG, 25.5 mM) glucose, in the presence or absence of IGF-1 (10-500 nM), the PI-3 kinase/Akt inhibitor LY294002 (10 microM), the mTOR inhibitor rapamycin (20 microM) or the calcineurin inhibitors cyclosporin A (5 microM) or FK506 (10 mg/l). |
| 240 | 16135669 | Western blot analysis indicated that HG and IGF-1 stimulated phosphorylation of Akt and mTOR. |
| 241 | 16135669 | However, the HG-induced alterations in phosphorylation of Akt, mTOR, p70s6k and GSK-3beta were significantly reversed by IGF-1. |
| 242 | 16135669 | Protein expression of Akt, mTOR, p70s6k, GSK-3beta, SERCA2a and phospholamban was unaffected by HG, IGF-1 or rapamycin. |
| 243 | 16135669 | Collectively, our data suggest that IGF-1 may provide cardiac protection against glucose in part through a PI-3 kinase/Akt/mTOR/ p70s6k-dependent and calcineurin-independent pathway. |
| 244 | 16135669 | Inhibition of PI-3 kinase/Akt/mTOR, but not calcineurin signaling, reverses insulin-like growth factor I-induced protection against glucose toxicity in cardiomyocyte contractile function. |
| 245 | 16135669 | Insulin-like growth factor-I (IGF-1) ameliorates cardiac dysfunction in diabetes although the mechanism of action remains poorly understood. |
| 246 | 16135669 | This study examined the role of PI-3 kinase/Akt/mammalian target of rapamycin (mTOR) and calcineurin pathways in cardiac effects of IGF-1 against glucose toxicity. |
| 247 | 16135669 | Adult rat ventricular myocytes were cultured for 8 h with either normal (NG, 5.5 mM) or high (HG, 25.5 mM) glucose, in the presence or absence of IGF-1 (10-500 nM), the PI-3 kinase/Akt inhibitor LY294002 (10 microM), the mTOR inhibitor rapamycin (20 microM) or the calcineurin inhibitors cyclosporin A (5 microM) or FK506 (10 mg/l). |
| 248 | 16135669 | Western blot analysis indicated that HG and IGF-1 stimulated phosphorylation of Akt and mTOR. |
| 249 | 16135669 | However, the HG-induced alterations in phosphorylation of Akt, mTOR, p70s6k and GSK-3beta were significantly reversed by IGF-1. |
| 250 | 16135669 | Protein expression of Akt, mTOR, p70s6k, GSK-3beta, SERCA2a and phospholamban was unaffected by HG, IGF-1 or rapamycin. |
| 251 | 16135669 | Collectively, our data suggest that IGF-1 may provide cardiac protection against glucose in part through a PI-3 kinase/Akt/mTOR/ p70s6k-dependent and calcineurin-independent pathway. |
| 252 | 16176184 | Insulin inhibits GSK3 by promoting phosphorylation of a serine residue (Ser-21 in GSK3alpha, Ser-9 in GSK3beta), thereby relieving GSK3 inhibition of glycogen synthesis in muscle. |
| 253 | 16176184 | GSK3 inhibition in liver reduces expression of the gluconeogenic genes PEPCK (phosphoenolpyruvate carboxykinase), G6Pase (glucose-6-phosphatase), as well as IGFBP1 (insulin-like growth factor binding protein-1). |
| 254 | 16176184 | Interestingly, insulin injection of wild-type mice, which activates PKB (protein kinase B) and inhibits GSK3 to a greater degree than feeding (50% versus 25%), does not repress these genes. |
| 255 | 16227617 | Mice with muscle-specific knockout of the Glut4 glucose transporter (muscle-G4KO) are insulin resistant and mildly diabetic. |
| 256 | 16227617 | The increased glycogen synthase activity occurs in spite of decreased signaling through the insulin receptor substrate 1 (IRS-1)-phosphoinositide (PI) 3-kinase-Akt pathway and increased glycogen synthase kinase 3beta (GSK3beta) activity in the basal state. |
| 257 | 16227617 | In addition, the levels of two scaffolding proteins that are glycogen-targeting subunits of protein phosphatase 1 (PP1), the muscle-specific regulatory subunit (RGL) and the protein targeting to glycogen (PTG), are strikingly increased by 3.2- to 4.2-fold in muscle of muscle-G4KO mice compared to wild-type mice. |
| 258 | 16293347 | Thyrotropin-releasing hormone (TRH) is an endogenous antidepressant that reduces the expression of glycogen synthase kinase-3beta (GSK-3beta), an enzyme that hyperphosphorylates tau and is implicated in bipolar depression, diabetes and Alzheimer's disease. |
| 259 | 16374520 | Irs1 and Irs2 signaling is essential for hepatic glucose homeostasis and systemic growth. |
| 260 | 16374520 | Insulin receptor substrates, including Irs1 and Irs2, integrate insulin and IGF receptor signals with heterologous pathways to coordinate growth and metabolism. |
| 261 | 16374520 | Since Irs2 is thought to be especially important in hepatic nutrient homeostasis, we deleted Irs2 [corrected] from hepatocytes of WT mice (called LKO) or genetically insulin-resistant Irs1-/- mice (called LKO::Irs1-/-). |
| 262 | 16374520 | Hepatic insulin receptors were functional in all the mice, but insulin signaling via the Akt-FoxO1 pathway was reduced in Irs1-/- and LKO liver, and undetected in LKO::Irs1-/- liver; however, Gsk3beta phosphorylation (Ser9) and hepatic glycogen stores were nearly normal in all of the mice. |
| 263 | 16374520 | Regardless, few hepatic genes changed expression significantly in Irs1-/- or LKO mice, whereas hundreds of genes changed in LKO::Irs1-/- mice--including elevated levels of Pck1, G6pc, Ppargc1, Pparg, and Igfbp1. |
| 264 | 16374520 | Thus, signals delivered by Irs1 or Irs2 regulate hepatic gene expression that coordinates glucose homeostasis and systemic growth. |
| 265 | 16478782 | Regulation of dishevelled and beta-catenin in rat skeletal muscle: an alternative exercise-induced GSK-3beta signaling pathway. |
| 266 | 16478782 | beta-catenin is a multifunctional protein involved in cell-cell adhesion and the Wnt signaling pathway. beta-Catenin is activated upon its dephosphorylation, an event triggered by Dishevelled (Dvl)-mediated phosphorylation and deactivation of glycogen synthase kinase-3beta (GSK-3beta). |
| 267 | 16478782 | In skeletal muscle, both insulin and exercise decrease GSK-3beta activity, and we tested the hypothesis that these two stimuli regulate beta-catenin. |
| 268 | 16478782 | Immunoblotting demonstrated that Dvl, Axin, GSK-3beta, and beta-catenin proteins are expressed in rat red and white gastrocnemius muscles. |
| 269 | 16478782 | Treadmill running exercise in vivo significantly decreased beta-catenin phosphorylation in both muscle types, with complete dephosphorylation being elicited by maximal exercise. beta-Catenin dephosphorylation was intensity dependent, as dephosphorylation was highly correlated with muscle glycogen depletion during exercise (r(2) = 0.84, P < 0.001). beta-Catenin dephosphorylation was accompanied by increases in GSK-3beta Ser(9) phosphorylation and Dvl-GSK-3beta association. |
| 270 | 16478782 | In contrast to exercise, maximal insulin treatment (1 U/kg body wt) had no effect on skeletal muscle beta-catenin phosphorylation or Dvl-GSK-3beta interaction. |
| 271 | 16478782 | In conclusion, exercise in vivo, but not insulin, increases the association between Dvl and GSK-3beta in skeletal muscle, an event paralleled by beta-catenin dephosphorylation. |
| 272 | 16478782 | Regulation of dishevelled and beta-catenin in rat skeletal muscle: an alternative exercise-induced GSK-3beta signaling pathway. |
| 273 | 16478782 | beta-catenin is a multifunctional protein involved in cell-cell adhesion and the Wnt signaling pathway. beta-Catenin is activated upon its dephosphorylation, an event triggered by Dishevelled (Dvl)-mediated phosphorylation and deactivation of glycogen synthase kinase-3beta (GSK-3beta). |
| 274 | 16478782 | In skeletal muscle, both insulin and exercise decrease GSK-3beta activity, and we tested the hypothesis that these two stimuli regulate beta-catenin. |
| 275 | 16478782 | Immunoblotting demonstrated that Dvl, Axin, GSK-3beta, and beta-catenin proteins are expressed in rat red and white gastrocnemius muscles. |
| 276 | 16478782 | Treadmill running exercise in vivo significantly decreased beta-catenin phosphorylation in both muscle types, with complete dephosphorylation being elicited by maximal exercise. beta-Catenin dephosphorylation was intensity dependent, as dephosphorylation was highly correlated with muscle glycogen depletion during exercise (r(2) = 0.84, P < 0.001). beta-Catenin dephosphorylation was accompanied by increases in GSK-3beta Ser(9) phosphorylation and Dvl-GSK-3beta association. |
| 277 | 16478782 | In contrast to exercise, maximal insulin treatment (1 U/kg body wt) had no effect on skeletal muscle beta-catenin phosphorylation or Dvl-GSK-3beta interaction. |
| 278 | 16478782 | In conclusion, exercise in vivo, but not insulin, increases the association between Dvl and GSK-3beta in skeletal muscle, an event paralleled by beta-catenin dephosphorylation. |
| 279 | 16478782 | Regulation of dishevelled and beta-catenin in rat skeletal muscle: an alternative exercise-induced GSK-3beta signaling pathway. |
| 280 | 16478782 | beta-catenin is a multifunctional protein involved in cell-cell adhesion and the Wnt signaling pathway. beta-Catenin is activated upon its dephosphorylation, an event triggered by Dishevelled (Dvl)-mediated phosphorylation and deactivation of glycogen synthase kinase-3beta (GSK-3beta). |
| 281 | 16478782 | In skeletal muscle, both insulin and exercise decrease GSK-3beta activity, and we tested the hypothesis that these two stimuli regulate beta-catenin. |
| 282 | 16478782 | Immunoblotting demonstrated that Dvl, Axin, GSK-3beta, and beta-catenin proteins are expressed in rat red and white gastrocnemius muscles. |
| 283 | 16478782 | Treadmill running exercise in vivo significantly decreased beta-catenin phosphorylation in both muscle types, with complete dephosphorylation being elicited by maximal exercise. beta-Catenin dephosphorylation was intensity dependent, as dephosphorylation was highly correlated with muscle glycogen depletion during exercise (r(2) = 0.84, P < 0.001). beta-Catenin dephosphorylation was accompanied by increases in GSK-3beta Ser(9) phosphorylation and Dvl-GSK-3beta association. |
| 284 | 16478782 | In contrast to exercise, maximal insulin treatment (1 U/kg body wt) had no effect on skeletal muscle beta-catenin phosphorylation or Dvl-GSK-3beta interaction. |
| 285 | 16478782 | In conclusion, exercise in vivo, but not insulin, increases the association between Dvl and GSK-3beta in skeletal muscle, an event paralleled by beta-catenin dephosphorylation. |
| 286 | 16478782 | Regulation of dishevelled and beta-catenin in rat skeletal muscle: an alternative exercise-induced GSK-3beta signaling pathway. |
| 287 | 16478782 | beta-catenin is a multifunctional protein involved in cell-cell adhesion and the Wnt signaling pathway. beta-Catenin is activated upon its dephosphorylation, an event triggered by Dishevelled (Dvl)-mediated phosphorylation and deactivation of glycogen synthase kinase-3beta (GSK-3beta). |
| 288 | 16478782 | In skeletal muscle, both insulin and exercise decrease GSK-3beta activity, and we tested the hypothesis that these two stimuli regulate beta-catenin. |
| 289 | 16478782 | Immunoblotting demonstrated that Dvl, Axin, GSK-3beta, and beta-catenin proteins are expressed in rat red and white gastrocnemius muscles. |
| 290 | 16478782 | Treadmill running exercise in vivo significantly decreased beta-catenin phosphorylation in both muscle types, with complete dephosphorylation being elicited by maximal exercise. beta-Catenin dephosphorylation was intensity dependent, as dephosphorylation was highly correlated with muscle glycogen depletion during exercise (r(2) = 0.84, P < 0.001). beta-Catenin dephosphorylation was accompanied by increases in GSK-3beta Ser(9) phosphorylation and Dvl-GSK-3beta association. |
| 291 | 16478782 | In contrast to exercise, maximal insulin treatment (1 U/kg body wt) had no effect on skeletal muscle beta-catenin phosphorylation or Dvl-GSK-3beta interaction. |
| 292 | 16478782 | In conclusion, exercise in vivo, but not insulin, increases the association between Dvl and GSK-3beta in skeletal muscle, an event paralleled by beta-catenin dephosphorylation. |
| 293 | 16478782 | Regulation of dishevelled and beta-catenin in rat skeletal muscle: an alternative exercise-induced GSK-3beta signaling pathway. |
| 294 | 16478782 | beta-catenin is a multifunctional protein involved in cell-cell adhesion and the Wnt signaling pathway. beta-Catenin is activated upon its dephosphorylation, an event triggered by Dishevelled (Dvl)-mediated phosphorylation and deactivation of glycogen synthase kinase-3beta (GSK-3beta). |
| 295 | 16478782 | In skeletal muscle, both insulin and exercise decrease GSK-3beta activity, and we tested the hypothesis that these two stimuli regulate beta-catenin. |
| 296 | 16478782 | Immunoblotting demonstrated that Dvl, Axin, GSK-3beta, and beta-catenin proteins are expressed in rat red and white gastrocnemius muscles. |
| 297 | 16478782 | Treadmill running exercise in vivo significantly decreased beta-catenin phosphorylation in both muscle types, with complete dephosphorylation being elicited by maximal exercise. beta-Catenin dephosphorylation was intensity dependent, as dephosphorylation was highly correlated with muscle glycogen depletion during exercise (r(2) = 0.84, P < 0.001). beta-Catenin dephosphorylation was accompanied by increases in GSK-3beta Ser(9) phosphorylation and Dvl-GSK-3beta association. |
| 298 | 16478782 | In contrast to exercise, maximal insulin treatment (1 U/kg body wt) had no effect on skeletal muscle beta-catenin phosphorylation or Dvl-GSK-3beta interaction. |
| 299 | 16478782 | In conclusion, exercise in vivo, but not insulin, increases the association between Dvl and GSK-3beta in skeletal muscle, an event paralleled by beta-catenin dephosphorylation. |
| 300 | 16478782 | Regulation of dishevelled and beta-catenin in rat skeletal muscle: an alternative exercise-induced GSK-3beta signaling pathway. |
| 301 | 16478782 | beta-catenin is a multifunctional protein involved in cell-cell adhesion and the Wnt signaling pathway. beta-Catenin is activated upon its dephosphorylation, an event triggered by Dishevelled (Dvl)-mediated phosphorylation and deactivation of glycogen synthase kinase-3beta (GSK-3beta). |
| 302 | 16478782 | In skeletal muscle, both insulin and exercise decrease GSK-3beta activity, and we tested the hypothesis that these two stimuli regulate beta-catenin. |
| 303 | 16478782 | Immunoblotting demonstrated that Dvl, Axin, GSK-3beta, and beta-catenin proteins are expressed in rat red and white gastrocnemius muscles. |
| 304 | 16478782 | Treadmill running exercise in vivo significantly decreased beta-catenin phosphorylation in both muscle types, with complete dephosphorylation being elicited by maximal exercise. beta-Catenin dephosphorylation was intensity dependent, as dephosphorylation was highly correlated with muscle glycogen depletion during exercise (r(2) = 0.84, P < 0.001). beta-Catenin dephosphorylation was accompanied by increases in GSK-3beta Ser(9) phosphorylation and Dvl-GSK-3beta association. |
| 305 | 16478782 | In contrast to exercise, maximal insulin treatment (1 U/kg body wt) had no effect on skeletal muscle beta-catenin phosphorylation or Dvl-GSK-3beta interaction. |
| 306 | 16478782 | In conclusion, exercise in vivo, but not insulin, increases the association between Dvl and GSK-3beta in skeletal muscle, an event paralleled by beta-catenin dephosphorylation. |
| 307 | 16484495 | In experiments with cultured cells, we show here that GSK3beta phosphorylates and stabilizes the orphan nuclear receptor Rev-erbalpha, a negative component of the circadian clock. |
| 308 | 16530186 | We found that GSK3beta became more active (less phosphorylated at serine 9) via decreased Akt phosphorylation, in parallel to c-Jun NH2 terminal kinase activation, which correlated with increased activated caspase 3 and myocardial apoptosis 3 days after streptozotocin (STZ) injection in mice. |
| 309 | 16530186 | However, 28 days after STZ injection, GSK3beta became inactive, which correlated with the enhanced protein kinase C beta2 and p38 mitogen activated protein kinase expression, nuclear translocation of nuclear factor of activated T cells c3, cardiac hypertrophy and fibrosis. |
| 310 | 16530186 | We found that GSK3beta became more active (less phosphorylated at serine 9) via decreased Akt phosphorylation, in parallel to c-Jun NH2 terminal kinase activation, which correlated with increased activated caspase 3 and myocardial apoptosis 3 days after streptozotocin (STZ) injection in mice. |
| 311 | 16530186 | However, 28 days after STZ injection, GSK3beta became inactive, which correlated with the enhanced protein kinase C beta2 and p38 mitogen activated protein kinase expression, nuclear translocation of nuclear factor of activated T cells c3, cardiac hypertrophy and fibrosis. |
| 312 | 16687499 | In good agreement, mice with conditional overexpression of GSK-3 in forebrain neurons (Tet/GSK-3beta mice) recapitulate aspects of AD neuropathology such as tau hyperphosphorylation, apoptotic neuronal death, and reactive astrocytosis as well as spatial learning deficit. |
| 313 | 16757548 | GSK-3alpha and GSK-3beta expression decreased in adipocytes (P < 0.05), whereas GSK-3alpha protein expression increased in skeletal muscle (P < 0.05). |
| 314 | 16787414 | In addition to being a target for diabetes, PPARgamma activation state has recently been shown to modulate beta-amyloid peptide (Abeta) production in cellular models relevant to Alzheimer's disease. |
| 315 | 16787414 | Furthermore, PPARgamma transcriptional activity did not appear to be responsible for decreased phosphorylation of tau. |
| 316 | 16787414 | Thus, we believe that the thiazolidinedione regulates tau phosphorylation through a PPARgamma-dependent/independent mechanism involving an Akt/glycogen synthase kinase-3(GSK-3beta)-independent signalling cascade: PDK1/p70S6K/mTor. |
| 317 | 16803855 | In addition, lack of Akt2 did not result in alterations in basal Akt Thr(308) or basal and contraction-stimulated glycogen synthase kinase-3beta (GSK-3beta) Ser(9) phosphorylation, glycogen synthase phosphorylation, or glycogen synthase activity. |
| 318 | 16803855 | In contrast, in situ contraction failed to elicit normal increases in Akt T-loop Thr(308) phosphorylation and GSK-3alpha Ser(21) phosphorylation in tibialis anterior muscles from Akt2-deficient animals. |
| 319 | 16803855 | Our data establish a key role for Akt2 in the regulation of GSK-3alpha Ser(21) phosphorylation with contraction and add genetic evidence to support the separation of the intracellular pathways regulated by insulin and exercise that converge on glucose uptake and glycogen synthesis in skeletal muscle. |
| 320 | 16823721 | We have recently shown that 12(S)-hydroxyeicosatetraenoic acid plays a role in the organization of actin microfilaments in rat cardiomyocytes, and that inhibition of 12-lipoxygenase abrogates insulin-stimulated GLUT4 translocation in these cells. |
| 321 | 16823721 | Insulin-regulated serine phosphorylation of Akt and GSK3alpha and GSK3beta was unaltered in heart and skeletal muscle of knockout mice, suggesting unaltered insulin signaling. |
| 322 | 16823721 | Fractionation of hind limb muscles showed that insulin had induced a prominent translocation of GLUT4 to skeletal muscle plasma membranes in control mice. |
| 323 | 16823721 | However, perturbation of GLUT4 translocation in skeletal muscle of knockout mice may indicate latent insulin resistance, and supports our hypothesis that eicosanoids are involved in insulin-mediated regulation of muscle glucose transport. |
| 324 | 16882729 | Caenorhabditis elegans ortholog of a diabetes susceptibility locus: oga-1 (O-GlcNAcase) knockout impacts O-GlcNAc cycling, metabolism, and dauer. |
| 325 | 16882729 | Two highly conserved enzymes (O-GlcNAc transferase and O-GlcNAcase) catalyze the final steps in this nutrient-driven "hexosamine-signaling pathway." |
| 326 | 16882729 | Interfering with O-GlcNAc cycling with either oga-1(ok1207) or the O-GlcNAc transferase-null ogt-1(ok430) altered Ser- and Thr-phosphoprotein profiles and increased glycogen synthase kinase 3beta (GSK-3beta) levels. |
| 327 | 16882729 | These striking metabolic changes prompted us to examine the insulin-like signaling pathway controlling nutrient storage, longevity, and dauer formation in the C. elegans O-GlcNAc cycling mutants. |
| 328 | 16882729 | Our findings suggest that the enzymes of O-GlcNAc cycling "fine-tune" insulin-like signaling in response to nutrient flux. |
| 329 | 16882729 | The knockout of O-GlcNAcase (oga-1) in C. elegans mimics many of the metabolic and signaling changes associated with human insulin resistance and provides a genetically amenable model of non-insulin-dependent diabetes. |
| 330 | 16943306 | Wnt/beta-catenin signaling modulates survival of high glucose-stressed mesangial cells. |
| 331 | 16943306 | Whereas Wnt signaling has been found to regulate renal morphogenesis and pathogenesis, the biologic role of Wnt/beta-catenin signaling in controlling high glucose-induced mesangial cell apoptosis is not well defined. |
| 332 | 16943306 | Herein is reported that Wnt/beta-catenin signaling is required for protecting glomerular mesangial cells from high glucose-mediated cell apoptosis. |
| 333 | 16943306 | High glucose downregulated Wnt4 and Wnt5a expression and the subsequent nuclear translocation of beta-catenin, whereas it increased glycogen synthase kinase-3beta (GSK-3beta) and caspase-3 activities and apoptosis of glomerular mesangial cells. |
| 334 | 16943306 | Suppression of GSK-3beta activation or increase in nuclear beta-catenin by transfection of Wnt4 or Wnt5a or stable beta-catenin (S33Y) reversed Akt activation and reduced the high glucose-mediated caspase-3 cleavage and cell apoptosis. |
| 335 | 16943306 | Pharmacologic inhibition of GSK-3beta by recombinant Wnt5a or bromoindirubin-3'-oxime or LiCl increased Akt phosphorylation and beta-catenin translocation and abrogated high glucose-mediated proapoptotic activities. |
| 336 | 16943306 | Exogenous bromoindirubin-3'-oxime treatment reduced phospho-Ser(9)-GSK-3beta and beta-catenin expression and apoptosis of cells adjacent to glomeruli in diabetic kidneys and attenuated urinary protein secretion in diabetic rats. |
| 337 | 16943306 | Sustaining Wnt/beta-catenin signaling is beneficial for promoting survival of mesangial cells that are exposed to high glucose stress. |
| 338 | 16943306 | Wnt/beta-catenin signaling modulates survival of high glucose-stressed mesangial cells. |
| 339 | 16943306 | Whereas Wnt signaling has been found to regulate renal morphogenesis and pathogenesis, the biologic role of Wnt/beta-catenin signaling in controlling high glucose-induced mesangial cell apoptosis is not well defined. |
| 340 | 16943306 | Herein is reported that Wnt/beta-catenin signaling is required for protecting glomerular mesangial cells from high glucose-mediated cell apoptosis. |
| 341 | 16943306 | High glucose downregulated Wnt4 and Wnt5a expression and the subsequent nuclear translocation of beta-catenin, whereas it increased glycogen synthase kinase-3beta (GSK-3beta) and caspase-3 activities and apoptosis of glomerular mesangial cells. |
| 342 | 16943306 | Suppression of GSK-3beta activation or increase in nuclear beta-catenin by transfection of Wnt4 or Wnt5a or stable beta-catenin (S33Y) reversed Akt activation and reduced the high glucose-mediated caspase-3 cleavage and cell apoptosis. |
| 343 | 16943306 | Pharmacologic inhibition of GSK-3beta by recombinant Wnt5a or bromoindirubin-3'-oxime or LiCl increased Akt phosphorylation and beta-catenin translocation and abrogated high glucose-mediated proapoptotic activities. |
| 344 | 16943306 | Exogenous bromoindirubin-3'-oxime treatment reduced phospho-Ser(9)-GSK-3beta and beta-catenin expression and apoptosis of cells adjacent to glomeruli in diabetic kidneys and attenuated urinary protein secretion in diabetic rats. |
| 345 | 16943306 | Sustaining Wnt/beta-catenin signaling is beneficial for promoting survival of mesangial cells that are exposed to high glucose stress. |
| 346 | 16943306 | Wnt/beta-catenin signaling modulates survival of high glucose-stressed mesangial cells. |
| 347 | 16943306 | Whereas Wnt signaling has been found to regulate renal morphogenesis and pathogenesis, the biologic role of Wnt/beta-catenin signaling in controlling high glucose-induced mesangial cell apoptosis is not well defined. |
| 348 | 16943306 | Herein is reported that Wnt/beta-catenin signaling is required for protecting glomerular mesangial cells from high glucose-mediated cell apoptosis. |
| 349 | 16943306 | High glucose downregulated Wnt4 and Wnt5a expression and the subsequent nuclear translocation of beta-catenin, whereas it increased glycogen synthase kinase-3beta (GSK-3beta) and caspase-3 activities and apoptosis of glomerular mesangial cells. |
| 350 | 16943306 | Suppression of GSK-3beta activation or increase in nuclear beta-catenin by transfection of Wnt4 or Wnt5a or stable beta-catenin (S33Y) reversed Akt activation and reduced the high glucose-mediated caspase-3 cleavage and cell apoptosis. |
| 351 | 16943306 | Pharmacologic inhibition of GSK-3beta by recombinant Wnt5a or bromoindirubin-3'-oxime or LiCl increased Akt phosphorylation and beta-catenin translocation and abrogated high glucose-mediated proapoptotic activities. |
| 352 | 16943306 | Exogenous bromoindirubin-3'-oxime treatment reduced phospho-Ser(9)-GSK-3beta and beta-catenin expression and apoptosis of cells adjacent to glomeruli in diabetic kidneys and attenuated urinary protein secretion in diabetic rats. |
| 353 | 16943306 | Sustaining Wnt/beta-catenin signaling is beneficial for promoting survival of mesangial cells that are exposed to high glucose stress. |
| 354 | 16943306 | Wnt/beta-catenin signaling modulates survival of high glucose-stressed mesangial cells. |
| 355 | 16943306 | Whereas Wnt signaling has been found to regulate renal morphogenesis and pathogenesis, the biologic role of Wnt/beta-catenin signaling in controlling high glucose-induced mesangial cell apoptosis is not well defined. |
| 356 | 16943306 | Herein is reported that Wnt/beta-catenin signaling is required for protecting glomerular mesangial cells from high glucose-mediated cell apoptosis. |
| 357 | 16943306 | High glucose downregulated Wnt4 and Wnt5a expression and the subsequent nuclear translocation of beta-catenin, whereas it increased glycogen synthase kinase-3beta (GSK-3beta) and caspase-3 activities and apoptosis of glomerular mesangial cells. |
| 358 | 16943306 | Suppression of GSK-3beta activation or increase in nuclear beta-catenin by transfection of Wnt4 or Wnt5a or stable beta-catenin (S33Y) reversed Akt activation and reduced the high glucose-mediated caspase-3 cleavage and cell apoptosis. |
| 359 | 16943306 | Pharmacologic inhibition of GSK-3beta by recombinant Wnt5a or bromoindirubin-3'-oxime or LiCl increased Akt phosphorylation and beta-catenin translocation and abrogated high glucose-mediated proapoptotic activities. |
| 360 | 16943306 | Exogenous bromoindirubin-3'-oxime treatment reduced phospho-Ser(9)-GSK-3beta and beta-catenin expression and apoptosis of cells adjacent to glomeruli in diabetic kidneys and attenuated urinary protein secretion in diabetic rats. |
| 361 | 16943306 | Sustaining Wnt/beta-catenin signaling is beneficial for promoting survival of mesangial cells that are exposed to high glucose stress. |
| 362 | 16945017 | A cellular assay for measuring the inhibition of glycogen synthase kinase-3 via the accumulation of beta-catenin in Chinese hamster ovary clone K1 cells. |
| 363 | 16945017 | Glycogen synthase kinase-3 (GSK3) is a serine-threonine protein kinase that exists as two isozymes, GSK3alpha and GSK3beta. |
| 364 | 16945017 | We describe the development of a cell-based assay designed to measure the activity of GSK3 by directly measuring the accumulation of beta-catenin in Chinese hamster ovary clone K1 (CHOK1) cells. |
| 365 | 16945017 | Beta-catenin levels were assessed using an antibody-based staining protocol with a luminometric readout. |
| 366 | 16960890 | Long-term effects of tumor necrosis factor-alpha treatment on insulin signaling pathway in HepG2 cells and HepG2 cells overexpressing constitutively active Akt/PKB. |
| 367 | 16960890 | Tumor necrosis factor-alpha (TNF-alpha) mediated attenuation of insulin signaling pathway is an important cause in several disorders like obesity, obesity linked diabetes mellitus. |
| 368 | 16960890 | In the present study, the effects of long-term TNF-alpha (1 ng/ml) exposure on the components of insulin signaling pathway in HepG2 and HepG2 cells overexpressing constitutively active Akt1/PKB-alpha (HepG2-CA-Akt/PKB) have been investigated. |
| 369 | 16960890 | In parental HepG2 cells, TNF-alpha treatment for 24 h reduced the phosphorylation of Akt1/PKB-alpha and GSK-3beta and under these conditions cells also showed reduced insulin responsiveness in terms of Akt1/PKB-alpha and GSK-3beta phosphorylation. |
| 370 | 16960890 | TNF-alpha pre-incubated HepG2-CA-Akt/PKB cells showed lower reduction in Akt1/PKB-alpha and GSK-3beta phosphorylation and insulin responsiveness after 24 h as compared to parental HepG2 cells. |
| 371 | 16960890 | We report that the long-term TNF-alpha pre-incubation in both parental HepG2 and HepG2-CA-Akt/PKB-alpha cells leads to the reduction in the levels of IRS-1 without altering the levels of IRS-2. |
| 372 | 16960890 | In order to understand the reason for the differential insulin resistance in both the cell types, the effect of long-term TNF-alpha treatment on the proteins upstream to Akt/PKB was investigated. |
| 373 | 16960890 | TNF-alpha pre-incubation also showed reduced insulin-stimulated Tyr phosphorylation of insulin receptor (IR-beta) in both the cell types, moreover hyperphosphorylation of IRS-1 at Ser 312 residue was observed in TNF-alpha pre-incubated cells. |
| 374 | 16960890 | As hyperphosphorylation of IRS-1 at Ser 312 can induce its degradation, it is possible that reduced insulin responsiveness after long-term TNF-alpha pre-incubation observed in this study is due to the decrease in IRS-1 levels. |
| 375 | 16960890 | Long-term effects of tumor necrosis factor-alpha treatment on insulin signaling pathway in HepG2 cells and HepG2 cells overexpressing constitutively active Akt/PKB. |
| 376 | 16960890 | Tumor necrosis factor-alpha (TNF-alpha) mediated attenuation of insulin signaling pathway is an important cause in several disorders like obesity, obesity linked diabetes mellitus. |
| 377 | 16960890 | In the present study, the effects of long-term TNF-alpha (1 ng/ml) exposure on the components of insulin signaling pathway in HepG2 and HepG2 cells overexpressing constitutively active Akt1/PKB-alpha (HepG2-CA-Akt/PKB) have been investigated. |
| 378 | 16960890 | In parental HepG2 cells, TNF-alpha treatment for 24 h reduced the phosphorylation of Akt1/PKB-alpha and GSK-3beta and under these conditions cells also showed reduced insulin responsiveness in terms of Akt1/PKB-alpha and GSK-3beta phosphorylation. |
| 379 | 16960890 | TNF-alpha pre-incubated HepG2-CA-Akt/PKB cells showed lower reduction in Akt1/PKB-alpha and GSK-3beta phosphorylation and insulin responsiveness after 24 h as compared to parental HepG2 cells. |
| 380 | 16960890 | We report that the long-term TNF-alpha pre-incubation in both parental HepG2 and HepG2-CA-Akt/PKB-alpha cells leads to the reduction in the levels of IRS-1 without altering the levels of IRS-2. |
| 381 | 16960890 | In order to understand the reason for the differential insulin resistance in both the cell types, the effect of long-term TNF-alpha treatment on the proteins upstream to Akt/PKB was investigated. |
| 382 | 16960890 | TNF-alpha pre-incubation also showed reduced insulin-stimulated Tyr phosphorylation of insulin receptor (IR-beta) in both the cell types, moreover hyperphosphorylation of IRS-1 at Ser 312 residue was observed in TNF-alpha pre-incubated cells. |
| 383 | 16960890 | As hyperphosphorylation of IRS-1 at Ser 312 can induce its degradation, it is possible that reduced insulin responsiveness after long-term TNF-alpha pre-incubation observed in this study is due to the decrease in IRS-1 levels. |
| 384 | 16968709 | The orphan nuclear receptor Rev-erb alpha regulates circadian expression of plasminogen activator inhibitor type 1. |
| 385 | 16968709 | Plasminogen activator inhibitor type 1 (PAI-1) is a major physiologic regulator of the fibrinolytic system and has recently gained recognition as a modulator of inflammation and atherosclerosis. |
| 386 | 16968709 | We discovered that the orphan nuclear receptor Rev-erb alpha, a core component of the circadian loop, represses human PAI-1 gene expression through two Rev-erb alpha binding sites in the PAI-1 promoter. |
| 387 | 16968709 | Furthermore, glycogen synthase kinase 3beta (GSK3beta) contributes to pai-1 repression by phosphorylating and stabilizing Rev-erb alpha protein, which can be blocked by lithium. |
| 388 | 16968709 | Ectopic expression of a stabilized form of Rev-erb alpha that mimics GSK3beta phosphorylation dramatically dampened PAI-1 circadian oscillations. |
| 389 | 16968709 | The orphan nuclear receptor Rev-erb alpha regulates circadian expression of plasminogen activator inhibitor type 1. |
| 390 | 16968709 | Plasminogen activator inhibitor type 1 (PAI-1) is a major physiologic regulator of the fibrinolytic system and has recently gained recognition as a modulator of inflammation and atherosclerosis. |
| 391 | 16968709 | We discovered that the orphan nuclear receptor Rev-erb alpha, a core component of the circadian loop, represses human PAI-1 gene expression through two Rev-erb alpha binding sites in the PAI-1 promoter. |
| 392 | 16968709 | Furthermore, glycogen synthase kinase 3beta (GSK3beta) contributes to pai-1 repression by phosphorylating and stabilizing Rev-erb alpha protein, which can be blocked by lithium. |
| 393 | 16968709 | Ectopic expression of a stabilized form of Rev-erb alpha that mimics GSK3beta phosphorylation dramatically dampened PAI-1 circadian oscillations. |
| 394 | 16970914 | Among them, VO(3mpa)(2) was found to be the highest potent activator in inducing not only the phosphotyrosine levels of both IRbeta and IRS but also the activation of downstream kinases in the insulin receptor, such as Akt and GSK3beta, which in turn translocated the insulin-dependent GLUT4 to the plasma membrane. |
| 395 | 16970914 | Our present data indicate that both activation of insulin signaling pathway, which follows the GLUT4 translocation to the plasma membrane, and enhancement of glucose utilization by oxovanadium(IV) complexes cause the hypoglycemic effect in diabetic animals. |
| 396 | 17049785 | Here we review the role of insulin signaling in brain aging and AD, concluding that the signaling pathways downstream to neurotrophic and insulin signaling are defective and coincident with aberrant phosphorylation and translocation of key components, notably AKT and GSK3beta, but also rac> PAK signaling. |
| 397 | 17100578 | In mammals, GSK-3 is encoded by two genes, termed GSK-3alpha and GSK-3beta, that yield related but distinct protein-serine kinases. |
| 398 | 17192474 | The GSK3beta mediators, P-Akt, P-extracellular signal-related kinase (ERK)1, and P-signal transducer and activator of transcription (STAT)3, were also significantly reduced in untreated DBR compared with NDBR rats. |
| 399 | 17223256 | Regulation of SOCS-3 expression by leptin and its co-localization with insulin receptor in rat skeletal muscle cells. |
| 400 | 17223256 | Induction of suppressor of cytokine-3 (SOCS-3) protein expression has been implicated as a possible mechanism of leptin-induced insulin resistance. |
| 401 | 17223256 | Here, we show that treatment of rat skeletal muscle cells with leptin activated the SOCS-3 gene promoter and caused a time-dependent increase in both SOCS-3 mRNA and protein content. |
| 402 | 17223256 | Confocal microscopy demonstrated increased co-localization of SOCS-3 with insulin receptor in leptin-treated cells and we confirmed a direct interaction between these two proteins by showing increased coimmunoprecipitation of SOCS-3 and insulin receptor after exposure of cells to leptin. |
| 403 | 17223256 | However, the expected functional consequences were not observed, as we saw no change in basal or insulin-stimulated glucose uptake and phosphorylation of GSK3beta, Akt (T308 and S473) or ERK1/2. |
| 404 | 17223256 | In summary, leptin induced SOCS-3 expression and its association with the insulin receptor in rat skeletal muscle cells but functional significance of this increase was not apparent upon measuring glucose uptake. |
| 405 | 17293880 | In the absence of drug, GSK-3beta(FRB)*(/FRB)* mutants appear phenotypically identical to GSK-3beta-/- mutants. |
| 406 | 17329594 | Furthermore, the insulin- and eCG-stimulated phosphoinositide-3-OH kinase signaling events, which included phosphorylation of Akt/protein kinase B and glycogen synthase kinase 3-beta, were impaired, whereas mitogen-activated protein kinase signaling was preserved in Irs2 null ovaries. |
| 407 | 17329594 | These abnormalities were associated with reduced expression of cyclin D2 and increased CDKN1B levels, which indicates dysregulation of key components of the cell cycle apparatus implicated in ovarian function. |
| 408 | 17513702 | Effects of endurance exercise training on insulin signaling in human skeletal muscle: interactions at the level of phosphatidylinositol 3-kinase, Akt, and AS160. |
| 409 | 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. |
| 410 | 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). |
| 411 | 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). |
| 412 | 17513702 | In contrast, training reduced IRS-1-associated PI3-K activity (P < 0.05) in both basal and insulin-stimulated muscle tissue. |
| 413 | 17570255 | Therefore, we assessed the functionality of proximal and distal insulin signaling elements in isolated type I (slow-twitch oxidative) soleus muscles of ZDF rats after in vitro exposure to a selective GSK-3 inhibitor (1 micromol/L CT98014, K(i) <10 nmol/L for GSK-3alpha and GSK-3beta). |
| 414 | 17570255 | Maximally insulin-stimulated (5 mU/mL) GSK-3beta serine phosphorylation was significantly less (35%, P < .05) in soleus muscle of ZDF rats compared with insulin-sensitive lean Zucker rats, indicating GSK-3 overactivity. |
| 415 | 17570255 | GSK-3 inhibition led to significant enhancement (28%) of insulin-stimulated glucose transport activity that was associated with significant up-regulation of tyrosine phosphorylation of IR (52%) and IRS-1 (50%), and with enhanced Akt Ser473 phosphorylation (48%) and GSK-3beta Ser9 phosphorylation (36%). |
| 416 | 17570255 | Moreover, the selective GSK-3 inhibitor induced a significant reduction in the phosphorylation of IRS-1 Ser307 (26%) and c-jun N-terminal kinases 1 and 2 (31%), a mediator of IRS-1 Ser307 phosphorylation. |
| 417 | 17570255 | These results indicate that selective inhibition of GSK-3 activity in type I skeletal muscle from overtly diabetic ZDF rats enhances IRS-1-dependent insulin signaling, possibly by a decrease in c-jun N-terminal kinase activation and a diminution of the deleterious effects of IRS-1 Ser307 phosphorylation. |
| 418 | 17570255 | Therefore, we assessed the functionality of proximal and distal insulin signaling elements in isolated type I (slow-twitch oxidative) soleus muscles of ZDF rats after in vitro exposure to a selective GSK-3 inhibitor (1 micromol/L CT98014, K(i) <10 nmol/L for GSK-3alpha and GSK-3beta). |
| 419 | 17570255 | Maximally insulin-stimulated (5 mU/mL) GSK-3beta serine phosphorylation was significantly less (35%, P < .05) in soleus muscle of ZDF rats compared with insulin-sensitive lean Zucker rats, indicating GSK-3 overactivity. |
| 420 | 17570255 | GSK-3 inhibition led to significant enhancement (28%) of insulin-stimulated glucose transport activity that was associated with significant up-regulation of tyrosine phosphorylation of IR (52%) and IRS-1 (50%), and with enhanced Akt Ser473 phosphorylation (48%) and GSK-3beta Ser9 phosphorylation (36%). |
| 421 | 17570255 | Moreover, the selective GSK-3 inhibitor induced a significant reduction in the phosphorylation of IRS-1 Ser307 (26%) and c-jun N-terminal kinases 1 and 2 (31%), a mediator of IRS-1 Ser307 phosphorylation. |
| 422 | 17570255 | These results indicate that selective inhibition of GSK-3 activity in type I skeletal muscle from overtly diabetic ZDF rats enhances IRS-1-dependent insulin signaling, possibly by a decrease in c-jun N-terminal kinase activation and a diminution of the deleterious effects of IRS-1 Ser307 phosphorylation. |
| 423 | 17570255 | Therefore, we assessed the functionality of proximal and distal insulin signaling elements in isolated type I (slow-twitch oxidative) soleus muscles of ZDF rats after in vitro exposure to a selective GSK-3 inhibitor (1 micromol/L CT98014, K(i) <10 nmol/L for GSK-3alpha and GSK-3beta). |
| 424 | 17570255 | Maximally insulin-stimulated (5 mU/mL) GSK-3beta serine phosphorylation was significantly less (35%, P < .05) in soleus muscle of ZDF rats compared with insulin-sensitive lean Zucker rats, indicating GSK-3 overactivity. |
| 425 | 17570255 | GSK-3 inhibition led to significant enhancement (28%) of insulin-stimulated glucose transport activity that was associated with significant up-regulation of tyrosine phosphorylation of IR (52%) and IRS-1 (50%), and with enhanced Akt Ser473 phosphorylation (48%) and GSK-3beta Ser9 phosphorylation (36%). |
| 426 | 17570255 | Moreover, the selective GSK-3 inhibitor induced a significant reduction in the phosphorylation of IRS-1 Ser307 (26%) and c-jun N-terminal kinases 1 and 2 (31%), a mediator of IRS-1 Ser307 phosphorylation. |
| 427 | 17570255 | These results indicate that selective inhibition of GSK-3 activity in type I skeletal muscle from overtly diabetic ZDF rats enhances IRS-1-dependent insulin signaling, possibly by a decrease in c-jun N-terminal kinase activation and a diminution of the deleterious effects of IRS-1 Ser307 phosphorylation. |
| 428 | 17577098 | Effects of PPAR-gamma knock-down and hyperglycemia on insulin signaling in vascular smooth muscle cells from hypertensive rats. |
| 429 | 17577098 | Peroxisome proliferator-activated receptor (PPAR)-gamma, a target in the treatment of diabetes, improves insulin sensitivity and exerts cardiovascular protective effects by mechanisms that are not completely elucidated. |
| 430 | 17577098 | To investigate underlying molecular mechanisms responsible for PPAR-gamma-associated vascular insulin signaling in hypertension, we tested whether PPAR-gamma downregulation in vascular smooth muscle cells (VSMC) from WKY and SHRSP rats would decrease insulin signaling and glucose uptake and whether this response would be worsened by hyperglycemia to a greater extent in VSMC of hypertensive origin. |
| 431 | 17577098 | Passaged mesenteric artery VSMC grown in euglycemic (5.5 mmol/L) or hyperglycemic media (25.0 mmol/L) were treated with PPAR-gamma-siRNA (5 nmol/L), PPAR-gamma antagonist (GW-9662, 10 micromol/L), or PPAR-gamma activator (rosiglitazone, 10 micromol/L) in the presence or absence of insulin (100 nmol/L). |
| 432 | 17577098 | Immunoblotting revealed that hyperglycemia and PPAR-gamma inhibition significantly (P < 0.001) decreased insulin-stimulated insulin receptor (IR)-beta, Akt, and glycogen synthase kinase (GSK)-3beta phosphorylation, whereas phosphotyrosine phosphatase (PTP)-1B expression was increased in VSMC from both strains. |
| 433 | 17577098 | Rosiglitazone tended to increase insulin-mediated IR-beta, Akt, and GSK-3beta phosphorylation in VSMC from both strains, whereas insulin-induced PTP-1B expression was reduced by hyperglycemia. |
| 434 | 17577098 | Insulin-stimulated GLUT-4 expression and glucose transport were attenuated by hyperglycemia in both VSMC. |
| 435 | 17577098 | These data suggest that PPAR-gamma inhibition results in decreased insulin signaling, particularly in SHR, in an IR-beta phosphorylation-dependent manner. |
| 436 | 17652946 | Glycogen synthase kinase 3beta (GSK3beta) is a well-known marker and potential therapeutic target in non-insulin-dependent diabetes mellitus and Alzheimer's disease. |
| 437 | 17652946 | The NRIKA uses a sequential combination of immunoprecipitations to isolate GSK3beta in sample cells' lysates, and an in vitro kinase reaction that uses recombinant beta-catenin protein (substrate) and nonradioisotopic ATP, followed by immunoblotting to detect beta-catenin phosphorylated in serine 33, 37 and/or threonine 41 residues. |
| 438 | 17652946 | The NRIKA provides a basis for evolving a high-throughput tool for testing substances for GSK3beta inhibition, and for screening and identifying novel GSK3beta inhibitors with a view to discovering drugs for treatment of cancer as well as non-insulin-dependent diabetes mellitus and Alzheimer's disease. |
| 439 | 17652946 | Glycogen synthase kinase 3beta (GSK3beta) is a well-known marker and potential therapeutic target in non-insulin-dependent diabetes mellitus and Alzheimer's disease. |
| 440 | 17652946 | The NRIKA uses a sequential combination of immunoprecipitations to isolate GSK3beta in sample cells' lysates, and an in vitro kinase reaction that uses recombinant beta-catenin protein (substrate) and nonradioisotopic ATP, followed by immunoblotting to detect beta-catenin phosphorylated in serine 33, 37 and/or threonine 41 residues. |
| 441 | 17652946 | The NRIKA provides a basis for evolving a high-throughput tool for testing substances for GSK3beta inhibition, and for screening and identifying novel GSK3beta inhibitors with a view to discovering drugs for treatment of cancer as well as non-insulin-dependent diabetes mellitus and Alzheimer's disease. |
| 442 | 17652946 | Glycogen synthase kinase 3beta (GSK3beta) is a well-known marker and potential therapeutic target in non-insulin-dependent diabetes mellitus and Alzheimer's disease. |
| 443 | 17652946 | The NRIKA uses a sequential combination of immunoprecipitations to isolate GSK3beta in sample cells' lysates, and an in vitro kinase reaction that uses recombinant beta-catenin protein (substrate) and nonradioisotopic ATP, followed by immunoblotting to detect beta-catenin phosphorylated in serine 33, 37 and/or threonine 41 residues. |
| 444 | 17652946 | The NRIKA provides a basis for evolving a high-throughput tool for testing substances for GSK3beta inhibition, and for screening and identifying novel GSK3beta inhibitors with a view to discovering drugs for treatment of cancer as well as non-insulin-dependent diabetes mellitus and Alzheimer's disease. |
| 445 | 17698034 | Rat hepatocytes in primary culture exhibited a rightward shift of the insulin dose-response curve for PKB phosphorylation during culture with palmitate. |
| 446 | 17698034 | The insulin-stimulated phosphorylation of GSK-3beta, a metabolic substrate of PKB, was diminished in palmitate hepatocytes. |
| 447 | 17698034 | Metformin treatment of the hepatocytes resulted in activation of the AMP-activated kinase, attenuation of the mTOR/S6K1 pathway, reduction of IRS-1 phosphorylation, and a leftward shift in the insulin dose-response curve for PKB activation. |
| 448 | 17765928 | Catalase alleviates cardiomyocyte dysfunction in diabetes: role of Akt, Forkhead transcriptional factor and silent information regulator 2. |
| 449 | 17765928 | Western blot analysis revealed that diabetes reduced Akt phosphorylation, enhanced the silent information regulator 2 (Sirt2), and upregulated Forkhead transcriptional factor Foxo3a as well as glycogen synthase kinase-3beta (GSK-3beta) and pGSK-3beta. |
| 450 | 17765928 | While catalase itself exhibited little effect on these proteins or their phosphorylation (with the exception of Sirt2), it significantly attenuated diabetes-induced alteration in pAkt, Foxo3a and Sirt2 without affecting GSK-3beta. |
| 451 | 17765928 | In summary, our data suggest potential roles of Akt, Foxo3a and Sirt2 in the onset of diabetic cardiomyopathy and the therapeutic potential of catalase. |
| 452 | 17765928 | Catalase alleviates cardiomyocyte dysfunction in diabetes: role of Akt, Forkhead transcriptional factor and silent information regulator 2. |
| 453 | 17765928 | Western blot analysis revealed that diabetes reduced Akt phosphorylation, enhanced the silent information regulator 2 (Sirt2), and upregulated Forkhead transcriptional factor Foxo3a as well as glycogen synthase kinase-3beta (GSK-3beta) and pGSK-3beta. |
| 454 | 17765928 | While catalase itself exhibited little effect on these proteins or their phosphorylation (with the exception of Sirt2), it significantly attenuated diabetes-induced alteration in pAkt, Foxo3a and Sirt2 without affecting GSK-3beta. |
| 455 | 17765928 | In summary, our data suggest potential roles of Akt, Foxo3a and Sirt2 in the onset of diabetic cardiomyopathy and the therapeutic potential of catalase. |
| 456 | 18036354 | In this study we examined the effect of the statin atorvastatin on the Akt/GSK-3beta pathway. |
| 457 | 18036354 | Our findings indicate that atorvastatin treatment for 15 days inhibited pressure overload-induced cardiac hypertrophy and prevented nuclear translocation of GATA4 and c-Jun and AP-1 DNA-binding activity. |
| 458 | 18036354 | In addition, atorvastatin treatment prevented the increase in the phosphorylation of Akt and GSK-3beta caused by cardiac hypertrophy, and this effect correlated with an increase in protein levels of phosphatase and tensin homolog on chromosome 10 (PTEN), which negatively regulates the phosphoinositide-3 kinase/Akt pathway. |
| 459 | 18036354 | To test whether the inhibitory effect of atorvastatin on Akt and GSK-3beta phosphorylation was direct we performed in vitro studies using embryonic rat heart-derived H9c2 cells, human AC16 cardiomyoblasts and neonatal rat cardiomyocytes. |
| 460 | 18036354 | Preincubation of cells with atorvastatin prevented Akt/GSK-3beta phosphorylation by different hypertrophic stimuli without affecting PTEN protein levels. |
| 461 | 18036354 | These findings point to a new potential anti-hypertrophic effect of statins, which can prevent activation of the Akt/GSK-3beta hypertrophic pathway by modulating PTEN activation by different mechanisms in chronic and acute treatments. |
| 462 | 18036354 | In this study we examined the effect of the statin atorvastatin on the Akt/GSK-3beta pathway. |
| 463 | 18036354 | Our findings indicate that atorvastatin treatment for 15 days inhibited pressure overload-induced cardiac hypertrophy and prevented nuclear translocation of GATA4 and c-Jun and AP-1 DNA-binding activity. |
| 464 | 18036354 | In addition, atorvastatin treatment prevented the increase in the phosphorylation of Akt and GSK-3beta caused by cardiac hypertrophy, and this effect correlated with an increase in protein levels of phosphatase and tensin homolog on chromosome 10 (PTEN), which negatively regulates the phosphoinositide-3 kinase/Akt pathway. |
| 465 | 18036354 | To test whether the inhibitory effect of atorvastatin on Akt and GSK-3beta phosphorylation was direct we performed in vitro studies using embryonic rat heart-derived H9c2 cells, human AC16 cardiomyoblasts and neonatal rat cardiomyocytes. |
| 466 | 18036354 | Preincubation of cells with atorvastatin prevented Akt/GSK-3beta phosphorylation by different hypertrophic stimuli without affecting PTEN protein levels. |
| 467 | 18036354 | These findings point to a new potential anti-hypertrophic effect of statins, which can prevent activation of the Akt/GSK-3beta hypertrophic pathway by modulating PTEN activation by different mechanisms in chronic and acute treatments. |
| 468 | 18036354 | In this study we examined the effect of the statin atorvastatin on the Akt/GSK-3beta pathway. |
| 469 | 18036354 | Our findings indicate that atorvastatin treatment for 15 days inhibited pressure overload-induced cardiac hypertrophy and prevented nuclear translocation of GATA4 and c-Jun and AP-1 DNA-binding activity. |
| 470 | 18036354 | In addition, atorvastatin treatment prevented the increase in the phosphorylation of Akt and GSK-3beta caused by cardiac hypertrophy, and this effect correlated with an increase in protein levels of phosphatase and tensin homolog on chromosome 10 (PTEN), which negatively regulates the phosphoinositide-3 kinase/Akt pathway. |
| 471 | 18036354 | To test whether the inhibitory effect of atorvastatin on Akt and GSK-3beta phosphorylation was direct we performed in vitro studies using embryonic rat heart-derived H9c2 cells, human AC16 cardiomyoblasts and neonatal rat cardiomyocytes. |
| 472 | 18036354 | Preincubation of cells with atorvastatin prevented Akt/GSK-3beta phosphorylation by different hypertrophic stimuli without affecting PTEN protein levels. |
| 473 | 18036354 | These findings point to a new potential anti-hypertrophic effect of statins, which can prevent activation of the Akt/GSK-3beta hypertrophic pathway by modulating PTEN activation by different mechanisms in chronic and acute treatments. |
| 474 | 18036354 | In this study we examined the effect of the statin atorvastatin on the Akt/GSK-3beta pathway. |
| 475 | 18036354 | Our findings indicate that atorvastatin treatment for 15 days inhibited pressure overload-induced cardiac hypertrophy and prevented nuclear translocation of GATA4 and c-Jun and AP-1 DNA-binding activity. |
| 476 | 18036354 | In addition, atorvastatin treatment prevented the increase in the phosphorylation of Akt and GSK-3beta caused by cardiac hypertrophy, and this effect correlated with an increase in protein levels of phosphatase and tensin homolog on chromosome 10 (PTEN), which negatively regulates the phosphoinositide-3 kinase/Akt pathway. |
| 477 | 18036354 | To test whether the inhibitory effect of atorvastatin on Akt and GSK-3beta phosphorylation was direct we performed in vitro studies using embryonic rat heart-derived H9c2 cells, human AC16 cardiomyoblasts and neonatal rat cardiomyocytes. |
| 478 | 18036354 | Preincubation of cells with atorvastatin prevented Akt/GSK-3beta phosphorylation by different hypertrophic stimuli without affecting PTEN protein levels. |
| 479 | 18036354 | These findings point to a new potential anti-hypertrophic effect of statins, which can prevent activation of the Akt/GSK-3beta hypertrophic pathway by modulating PTEN activation by different mechanisms in chronic and acute treatments. |
| 480 | 18036354 | In this study we examined the effect of the statin atorvastatin on the Akt/GSK-3beta pathway. |
| 481 | 18036354 | Our findings indicate that atorvastatin treatment for 15 days inhibited pressure overload-induced cardiac hypertrophy and prevented nuclear translocation of GATA4 and c-Jun and AP-1 DNA-binding activity. |
| 482 | 18036354 | In addition, atorvastatin treatment prevented the increase in the phosphorylation of Akt and GSK-3beta caused by cardiac hypertrophy, and this effect correlated with an increase in protein levels of phosphatase and tensin homolog on chromosome 10 (PTEN), which negatively regulates the phosphoinositide-3 kinase/Akt pathway. |
| 483 | 18036354 | To test whether the inhibitory effect of atorvastatin on Akt and GSK-3beta phosphorylation was direct we performed in vitro studies using embryonic rat heart-derived H9c2 cells, human AC16 cardiomyoblasts and neonatal rat cardiomyocytes. |
| 484 | 18036354 | Preincubation of cells with atorvastatin prevented Akt/GSK-3beta phosphorylation by different hypertrophic stimuli without affecting PTEN protein levels. |
| 485 | 18036354 | These findings point to a new potential anti-hypertrophic effect of statins, which can prevent activation of the Akt/GSK-3beta hypertrophic pathway by modulating PTEN activation by different mechanisms in chronic and acute treatments. |
| 486 | 18198341 | SCFCdc4 acts antagonistically to the PGC-1alpha transcriptional coactivator by targeting it for ubiquitin-mediated proteolysis. |
| 487 | 18198341 | Peroxisome proliferator-activated receptor gamma (PPARgamma) coactivator-1alpha (PGC-1alpha) is a highly regulated transcriptional coactivator that coordinates energy metabolism in mammals. |
| 488 | 18198341 | We identified SCF(Cdc4) as an E3 ubiquitin ligase that regulates PGC-1alpha through ubiquitin-mediated proteolysis. |
| 489 | 18198341 | PGC-1alpha contains two Cdc4 phosphodegrons that bind Cdc4 when phosphorylated by Glycogen Synthase Kinase 3beta (GSK3beta) and p38 MAPK, leading to SCF(Cdc4)-dependent ubiquitylation and proteasomal degradation of PGC-1alpha. |
| 490 | 18198341 | Furthermore, SCF(Cdc4) negatively regulates PGC-1alpha-dependent transcription. |
| 491 | 18198341 | These results suggest that attenuation of SCF(Cdc4)-dependent proteasomal degradation of PGC-1alpha has a role in mediating the PGC-1alpha-dependent transcriptional response to oxidative stress. |
| 492 | 18245813 | Iron depletion improves insulin resistance in patients with nonalcoholic fatty liver disease and diabetes and also stabilizes the hypoxia-inducible factor (HIF)-1, resulting in increased glucose uptake in vitro. |
| 493 | 18245813 | In HepG2 cells, deferoxamine stabilized HIF-1alpha and induced the constitutive glucose transporter Glut1 and the insulin receptor. |
| 494 | 18245813 | Up-regulation of insulin receptor by deferoxamine was mimicked by the intracellular iron chelator deferasirox and the hypoxia inducer CoCl2 and required the HIF-1 obligate partner ARNT/HIF-1beta. |
| 495 | 18245813 | Deferoxamine consistently increased the phosphorylation status of Akt/PKB and its targets FoxO1 and Gsk3beta, which mediate the effect of insulin on gluconeogenesis and glycogen synthesis, and up-regulated genes involved in glucose uptake and utilization. |
| 496 | 18245813 | Iron depletion of Sprague-Dawley rats increased HIF-1alpha expression, improved glucose clearance, and was associated with up-regulation of insulin receptor and Akt/PKB levels and of glucose transport in hepatic tissue. |
| 497 | 18268048 | STAT3 sensitizes insulin signaling by negatively regulating glycogen synthase kinase-3 beta. |
| 498 | 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). |
| 499 | 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. |
| 500 | 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. |
| 501 | 18288891 | Preservation of beta-cell mass in Gsk-3beta+/- Irs2-/- mice was accompanied by suppressed p27(kip1) levels and increased Pdx1 levels. |
| 502 | 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-/-). |
| 503 | 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). |
| 504 | 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. |
| 505 | 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. |
| 506 | 18288891 | Preservation of beta-cell mass in Gsk-3beta+/- Irs2-/- mice was accompanied by suppressed p27(kip1) levels and increased Pdx1 levels. |
| 507 | 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-/-). |
| 508 | 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). |
| 509 | 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. |
| 510 | 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. |
| 511 | 18288891 | Preservation of beta-cell mass in Gsk-3beta+/- Irs2-/- mice was accompanied by suppressed p27(kip1) levels and increased Pdx1 levels. |
| 512 | 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-/-). |
| 513 | 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). |
| 514 | 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. |
| 515 | 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. |
| 516 | 18288891 | Preservation of beta-cell mass in Gsk-3beta+/- Irs2-/- mice was accompanied by suppressed p27(kip1) levels and increased Pdx1 levels. |
| 517 | 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-/-). |
| 518 | 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). |
| 519 | 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. |
| 520 | 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. |
| 521 | 18288891 | Preservation of beta-cell mass in Gsk-3beta+/- Irs2-/- mice was accompanied by suppressed p27(kip1) levels and increased Pdx1 levels. |
| 522 | 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-/-). |
| 523 | 18296634 | Proteomic analysis of lithium-induced nephrogenic diabetes insipidus: mechanisms for aquaporin 2 down-regulation and cellular proliferation. |
| 524 | 18296634 | We demonstrate that members of several signaling pathways are activated by lithium treatment, including the PKB/Akt-kinase and the mitogen-activated protein kinases (MAPK), such as extracellular regulated kinase (ERK), c-Jun NH(2)-terminal kinase (JNK), and p38. |
| 525 | 18296634 | Lithium treatment increased the intracellular accumulation of beta-catenin in association with increased levels of phosphorylated glycogen synthase kinase type 3beta (GSK3beta). |
| 526 | 18339714 | Superoxide destabilization of beta-catenin augments apoptosis of high-glucose-stressed mesangial cells. |
| 527 | 18339714 | Although reactive oxygen radicals and Wnt signaling components are potent regulators that modulate renal tissue remodeling and morphogenesis, cross-talk between oxidative stress and Wnt/beta-catenin signaling in controlling high-glucose-impaired mesangial cell survival and renal function have not been tested. |
| 528 | 18339714 | In this study, high glucose induced Ras and Rac1 activation, superoxide burst, and Wnt5a/beta-catenin destabilization and subsequently promoted caspase-3 and poly (ADP-ribose) polymerase cleavage and apoptosis in mesangial cell cultures. |
| 529 | 18339714 | The pharmacological and genetic suppression of superoxide synthesis by superoxide dismutase and diphenyloniodium, dominant-negative Ras (S17N), and dominant-negative Rac1 (T17N) abrogated high-glucose-induced glycogen synthase kinase (GSK-3beta) activation and caspase-3 and poly (ADP-ribose) polymerase degradation. |
| 530 | 18339714 | Inactivation of Ras and Racl also reversed Wnt/beta-catenin expression and survival of mesangial cells. |
| 531 | 18339714 | Stabilization of beta-catenin by the transfection of stable beta-catenin (Delta45) and kinase-inactive GSK-3beta attenuated high-glucose-mediated mesangial cell apoptosis. |
| 532 | 18339714 | Immunohistological observation revealed that superoxide dismutase treatment abrogated diabetes-induced caspase-3 cleavage and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end-labeling (TUNEL) and increased Wnt5a/beta-catenin expression in renal glomeruli. |
| 533 | 18339714 | The Ras and Rac1 regulation of superoxide appeared to raise apoptotic activity by activating GSK-3beta and inhibiting Wnt5a/beta-catenin signaling. |
| 534 | 18339714 | Controlling oxidative stress and Wnt/beta-catenin signaling has potential for protecting renal tissue against the deleterious effect of high glucose. |
| 535 | 18339714 | Superoxide destabilization of beta-catenin augments apoptosis of high-glucose-stressed mesangial cells. |
| 536 | 18339714 | Although reactive oxygen radicals and Wnt signaling components are potent regulators that modulate renal tissue remodeling and morphogenesis, cross-talk between oxidative stress and Wnt/beta-catenin signaling in controlling high-glucose-impaired mesangial cell survival and renal function have not been tested. |
| 537 | 18339714 | In this study, high glucose induced Ras and Rac1 activation, superoxide burst, and Wnt5a/beta-catenin destabilization and subsequently promoted caspase-3 and poly (ADP-ribose) polymerase cleavage and apoptosis in mesangial cell cultures. |
| 538 | 18339714 | The pharmacological and genetic suppression of superoxide synthesis by superoxide dismutase and diphenyloniodium, dominant-negative Ras (S17N), and dominant-negative Rac1 (T17N) abrogated high-glucose-induced glycogen synthase kinase (GSK-3beta) activation and caspase-3 and poly (ADP-ribose) polymerase degradation. |
| 539 | 18339714 | Inactivation of Ras and Racl also reversed Wnt/beta-catenin expression and survival of mesangial cells. |
| 540 | 18339714 | Stabilization of beta-catenin by the transfection of stable beta-catenin (Delta45) and kinase-inactive GSK-3beta attenuated high-glucose-mediated mesangial cell apoptosis. |
| 541 | 18339714 | Immunohistological observation revealed that superoxide dismutase treatment abrogated diabetes-induced caspase-3 cleavage and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end-labeling (TUNEL) and increased Wnt5a/beta-catenin expression in renal glomeruli. |
| 542 | 18339714 | The Ras and Rac1 regulation of superoxide appeared to raise apoptotic activity by activating GSK-3beta and inhibiting Wnt5a/beta-catenin signaling. |
| 543 | 18339714 | Controlling oxidative stress and Wnt/beta-catenin signaling has potential for protecting renal tissue against the deleterious effect of high glucose. |
| 544 | 18339714 | Superoxide destabilization of beta-catenin augments apoptosis of high-glucose-stressed mesangial cells. |
| 545 | 18339714 | Although reactive oxygen radicals and Wnt signaling components are potent regulators that modulate renal tissue remodeling and morphogenesis, cross-talk between oxidative stress and Wnt/beta-catenin signaling in controlling high-glucose-impaired mesangial cell survival and renal function have not been tested. |
| 546 | 18339714 | In this study, high glucose induced Ras and Rac1 activation, superoxide burst, and Wnt5a/beta-catenin destabilization and subsequently promoted caspase-3 and poly (ADP-ribose) polymerase cleavage and apoptosis in mesangial cell cultures. |
| 547 | 18339714 | The pharmacological and genetic suppression of superoxide synthesis by superoxide dismutase and diphenyloniodium, dominant-negative Ras (S17N), and dominant-negative Rac1 (T17N) abrogated high-glucose-induced glycogen synthase kinase (GSK-3beta) activation and caspase-3 and poly (ADP-ribose) polymerase degradation. |
| 548 | 18339714 | Inactivation of Ras and Racl also reversed Wnt/beta-catenin expression and survival of mesangial cells. |
| 549 | 18339714 | Stabilization of beta-catenin by the transfection of stable beta-catenin (Delta45) and kinase-inactive GSK-3beta attenuated high-glucose-mediated mesangial cell apoptosis. |
| 550 | 18339714 | Immunohistological observation revealed that superoxide dismutase treatment abrogated diabetes-induced caspase-3 cleavage and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end-labeling (TUNEL) and increased Wnt5a/beta-catenin expression in renal glomeruli. |
| 551 | 18339714 | The Ras and Rac1 regulation of superoxide appeared to raise apoptotic activity by activating GSK-3beta and inhibiting Wnt5a/beta-catenin signaling. |
| 552 | 18339714 | Controlling oxidative stress and Wnt/beta-catenin signaling has potential for protecting renal tissue against the deleterious effect of high glucose. |
| 553 | 18430969 | Coordinated phosphorylation of insulin receptor substrate-1 by glycogen synthase kinase-3 and protein kinase C betaII in the diabetic fat tissue. |
| 554 | 18430969 | Overexpression of PKCalpha or PKCbetaII isoforms in cells enhanced IRS-1 phosphorylation at Ser(336) and Ser(332), and in vitro kinase assays verified that these two kinases directly phosphorylated IRS-1 at Ser(336). |
| 555 | 18430969 | Elevated levels of PKCbetaII were also associated with enhanced phosphorylation of IRS-1 at Ser(336/332) and elevated activity of GSK-3beta. |
| 556 | 18434357 | Insulin-stimulated insulin receptor (IR) Tyr1162/Tyr1163 phosphorylation and IR substrate (IRS)-1 Tyr612 phosphorylation were increased at least twofold over basal in GLYC rats with insulin and this increase was not significantly impaired in the LIP rats. |
| 557 | 18434357 | However, there was no insulin-stimulated protein kinase B (PKB) Ser473 or glycogen synthase kinase (GSK)-3beta Ser9 phosphorylation in the LIP rats, compared with at least a twofold increase over basal in GLYC rats for both proteins. c-Jun N-terminal kinase, inhibitor of kappa kinase beta and inhibitor of nuclear factor-kappaB phosphorylation and total protein expression, as well as Ser307-IRS-1 phosphorylation, were not altered by lipid infusion compared with GLYC infusion. |
| 558 | 18434357 | These data indicate that acute, physiological elevation in FFA has a greater impact on insulin signalling downstream of IR and IRS-1, at the level of PKB and GSK-3beta, and that under these conditions stress signalling pathways are not significantly stimulated. |
| 559 | 18434357 | Decreased PKB and GSK-3beta phosphorylation in RQ may therefore be primary determinants of the reduced insulin action observed in situations of acute FFA oversupply. |
| 560 | 18434357 | Insulin-stimulated insulin receptor (IR) Tyr1162/Tyr1163 phosphorylation and IR substrate (IRS)-1 Tyr612 phosphorylation were increased at least twofold over basal in GLYC rats with insulin and this increase was not significantly impaired in the LIP rats. |
| 561 | 18434357 | However, there was no insulin-stimulated protein kinase B (PKB) Ser473 or glycogen synthase kinase (GSK)-3beta Ser9 phosphorylation in the LIP rats, compared with at least a twofold increase over basal in GLYC rats for both proteins. c-Jun N-terminal kinase, inhibitor of kappa kinase beta and inhibitor of nuclear factor-kappaB phosphorylation and total protein expression, as well as Ser307-IRS-1 phosphorylation, were not altered by lipid infusion compared with GLYC infusion. |
| 562 | 18434357 | These data indicate that acute, physiological elevation in FFA has a greater impact on insulin signalling downstream of IR and IRS-1, at the level of PKB and GSK-3beta, and that under these conditions stress signalling pathways are not significantly stimulated. |
| 563 | 18434357 | Decreased PKB and GSK-3beta phosphorylation in RQ may therefore be primary determinants of the reduced insulin action observed in situations of acute FFA oversupply. |
| 564 | 18467435 | Role of Akt/GSK-3beta/beta-catenin transduction pathway in the muscle anti-atrophy action of insulin-like growth factor-I in glucocorticoid-treated rats. |
| 565 | 18467435 | Muscle atrophy induced by dexamethasone (dexa) administration occurred with a decrease in Akt (-53%; P<0.01) phosphorylation together with a decrease in beta-catenin protein levels (-40%; P<0.001). |
| 566 | 18467435 | Prevention of atrophy by IGF-I was associated with restoration of Akt phosphorylation and beta-catenin levels. |
| 567 | 18467435 | This hypertrophy was associated with an increase in phosphorylated GSK-3beta (+17%; P<0.05) and in beta-catenin content (+35%; P<0.05). |
| 568 | 18467435 | Furthermore, overexpression of a dominant-negative GSK-3beta or a stable form of beta-catenin increased fiber cross-sectional area by, respectively, 23% (P<0.001) and 29% (P<0.001) in dexa-treated rats, preventing completely the atrophic effect of GC. |
| 569 | 18467435 | In conclusion, this work indicates that Akt, GSK-3beta, and beta-catenin probably contribute together to the IGF-I anti-atrophic effect in GC-induced muscle atrophy. |
| 570 | 18467435 | Role of Akt/GSK-3beta/beta-catenin transduction pathway in the muscle anti-atrophy action of insulin-like growth factor-I in glucocorticoid-treated rats. |
| 571 | 18467435 | Muscle atrophy induced by dexamethasone (dexa) administration occurred with a decrease in Akt (-53%; P<0.01) phosphorylation together with a decrease in beta-catenin protein levels (-40%; P<0.001). |
| 572 | 18467435 | Prevention of atrophy by IGF-I was associated with restoration of Akt phosphorylation and beta-catenin levels. |
| 573 | 18467435 | This hypertrophy was associated with an increase in phosphorylated GSK-3beta (+17%; P<0.05) and in beta-catenin content (+35%; P<0.05). |
| 574 | 18467435 | Furthermore, overexpression of a dominant-negative GSK-3beta or a stable form of beta-catenin increased fiber cross-sectional area by, respectively, 23% (P<0.001) and 29% (P<0.001) in dexa-treated rats, preventing completely the atrophic effect of GC. |
| 575 | 18467435 | In conclusion, this work indicates that Akt, GSK-3beta, and beta-catenin probably contribute together to the IGF-I anti-atrophic effect in GC-induced muscle atrophy. |
| 576 | 18495798 | We investigated the potential of PKB/Akt to mediate the profibrotic bioactions of TGF-beta1 in kidney. |
| 577 | 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. |
| 578 | 18495798 | TGF-beta1 also stimulated increased Smad3 phosphorylation in these cells, a response that was insensitive to inhibition of PI3K or PKB/Akt. |
| 579 | 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. |
| 580 | 18495798 | These effects were blocked with inhibitors of PI3K and PKB/Akt. |
| 581 | 18495798 | Furthermore, overexpression of PTEN, the lipid phosphatase regulator of PKB/Akt activation, inhibited TGF-beta1-induced PKB/Akt activation. |
| 582 | 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. |
| 583 | 18495798 | We investigated the potential of PKB/Akt to mediate the profibrotic bioactions of TGF-beta1 in kidney. |
| 584 | 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. |
| 585 | 18495798 | TGF-beta1 also stimulated increased Smad3 phosphorylation in these cells, a response that was insensitive to inhibition of PI3K or PKB/Akt. |
| 586 | 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. |
| 587 | 18495798 | These effects were blocked with inhibitors of PI3K and PKB/Akt. |
| 588 | 18495798 | Furthermore, overexpression of PTEN, the lipid phosphatase regulator of PKB/Akt activation, inhibited TGF-beta1-induced PKB/Akt activation. |
| 589 | 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. |
| 590 | 18606491 | Glycogen synthase kinase 3beta (GSK3beta), a multifunctional serine/threonine kinase found in all eukaryotes, had been initially identified as a key regulator of insulin-dependent glycogen synthesis. |
| 591 | 18606491 | Aberrant regulation of GSK3beta has been implicated in a range of human pathologies including non-insulin-dependent diabetes mellitus, cardiovascular disease, some neurodegenerative diseases, and bipolar disorder. |
| 592 | 18606491 | Glycogen synthase kinase 3beta (GSK3beta), a multifunctional serine/threonine kinase found in all eukaryotes, had been initially identified as a key regulator of insulin-dependent glycogen synthesis. |
| 593 | 18606491 | Aberrant regulation of GSK3beta has been implicated in a range of human pathologies including non-insulin-dependent diabetes mellitus, cardiovascular disease, some neurodegenerative diseases, and bipolar disorder. |
| 594 | 18830417 | The hypertrophic myopathy was caused by cardiomyocyte hyperproliferation without hypertrophy and was associated with increased expression and nuclear localization of three regulators of proliferation - GATA4, cyclin D1, and c-Myc. |
| 595 | 18830417 | These studies, which we believe are the first in mammals to examine the role of GSK-3alpha and GSK-3beta in the heart using loss-of-function approaches, implicate GSK-3beta as a central regulator of embryonic cardiomyocyte proliferation and differentiation, as well as of outflow tract development. |
| 596 | 18838540 | Here, we discovered a new target for GSK-3beta phosphorylation: the human glucocorticoid receptor (GR). |
| 597 | 18838540 | Cells expressing a GR that is incapable of GSK-3beta phosphorylation had a redirection of the global transcriptional response to hormone, including the activation of additional signaling pathways, in part due to the altered ability of unphosphorylatable GR to recruit transcriptional cofactors CBP/p300 and the p65 (RelA) subunit of NF-kappaB. |
| 598 | 18838540 | Here, we discovered a new target for GSK-3beta phosphorylation: the human glucocorticoid receptor (GR). |
| 599 | 18838540 | Cells expressing a GR that is incapable of GSK-3beta phosphorylation had a redirection of the global transcriptional response to hormone, including the activation of additional signaling pathways, in part due to the altered ability of unphosphorylatable GR to recruit transcriptional cofactors CBP/p300 and the p65 (RelA) subunit of NF-kappaB. |
| 600 | 18839067 | Comparison of the active site residues of GSK-3alpha and GSK-3beta isoforms shows that all the key amino acids involved in polar interactions with the maleimides for the beta isoform are the same in the alpha isoform, except that Asp133 in the beta isoform is replaced by Glu196 in the alpha isoform. |
| 601 | 19013138 | Coexistences of insulin signaling-related proteins and choline acetyltransferase in neurons. |
| 602 | 19013138 | Using immunohistochemistry, the insulin signaling-related proteins, such as insulin receptor (InsR), insulin receptor substrate-1 (IRS-1), protein kinase B (PKB, also named Akt), glycogen synthase kinase-3beta (GSK-3beta) and insulin-degrading enzyme (IDE) were analysed. |
| 603 | 19081248 | Moreover, they showed the selectivity for GSK-3beta over other kinases with IC(50) values of 2 to 10microM or more Incubation of cells with KRM-191 with highly selective and potent inhibitory activity caused accumulation of beta-catenin, downstream of GSK-3beta signaling pathway, indicating that small molecule can prevent degradation of beta-catenin via GSK-3beta inhibition. |
| 604 | 19099246 | There are two homologous forms of glycogen synthase kinase (GSK)-3, GSK-3alpha and GSK-3beta, which play overlapping roles in the regulation of Wnt, Hedgehog, and insulin pathways, as well as the activation of nuclear factor (NF)-kappaB-mediated gene transcription. |
| 605 | 19244253 | Our findings show that the AKT/GSK-3beta dependent pathway plays an important role in mediating the protection of erythropoietin against diabetic neuropathy. |
| 606 | 19349976 | The endogenous inhibitor of Akt, CTMP, is critical to ischemia-induced neuronal death. |
| 607 | 19349976 | Although ischemia induced a marked phosphorylation and nuclear translocation of Akt, phosphorylated Akt was not active in post-ischemic neurons, as assessed by kinase assays and phosphorylation of the downstream targets GSK-3beta and FOXO3A. |
| 608 | 19365404 | Pancreas-specific Pten deficiency causes partial resistance to diabetes and elevated hepatic AKT signaling. |
| 609 | 19365404 | PTEN, a negative regulator of the phosphatidylinositol-3-kinase/AKT pathway, is an important modulator of insulin signaling. |
| 610 | 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. |
| 611 | 19365404 | We found that Pten loss in the pancreas causes the elevation of AKT signaling in the liver. |
| 612 | 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. |
| 613 | 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. |
| 614 | 19533653 | Atrogin-1, MuRF1, and FoXO, as well as phosphorylated GSK-3beta and 4E-BP1 are reduced in skeletal muscle of chronic spinal cord-injured patients. |
| 615 | 19533653 | Therefore, the aim of this study was to determine whether there was an increase in catabolic signaling targets, such as atrogin-1, muscle ring finger-1 (MuRF1), forkhead transcription factor (FoXO), and myostatin, and decreases in anabolic signaling targets, such as insulin-like growth factor (IGF), v-akt murine thymoma viral oncogene (Akt), glycogen synthase kinase-beta (GSK-3beta), mammalian target of rapamycin (mTOR), eukaryotic initiation factor 4E binding protein 1 (4E-BP1), and p70(s6kinase) in chronic complete SCI patients. |
| 616 | 19533653 | In SCI patients, when compared with controls, there was a significant reduction in mRNA levels of atrogin-1 (59%; P < 0.05), MuRF1 (55%; P < 0.05), and myostatin (46%; P < 0.01), and in protein levels of FoXO1 (72%; P < 0.05), FoXO3a (60%; P < 0.05), and atrogin-1 (36%; P < 0.05). |
| 617 | 19533653 | Decreases in the protein levels of IGF-1 (48%; P < 0.001) and phosphorylated GSK-3beta (54%; P < 0.05), 4E-BP1 (48%; P < 0.05), and p70(s6kinase) (60%; P = 0.1) were also observed, the latter three in an Akt- and mTOR-independent manner. |
| 618 | 19533653 | Reductions in atrogin-1, MuRF1, FoXO, and myostatin suggest the existence of an internal mechanism aimed at reducing further loss of muscle proteins during chronic SCI. |
| 619 | 19533653 | The downregulation of signaling proteins that regulate anabolism, such as IGF, GSK-3beta, and 4E-BP1, would reduce the ability to increase protein synthesis rates. |
| 620 | 19533653 | Atrogin-1, MuRF1, and FoXO, as well as phosphorylated GSK-3beta and 4E-BP1 are reduced in skeletal muscle of chronic spinal cord-injured patients. |
| 621 | 19533653 | Therefore, the aim of this study was to determine whether there was an increase in catabolic signaling targets, such as atrogin-1, muscle ring finger-1 (MuRF1), forkhead transcription factor (FoXO), and myostatin, and decreases in anabolic signaling targets, such as insulin-like growth factor (IGF), v-akt murine thymoma viral oncogene (Akt), glycogen synthase kinase-beta (GSK-3beta), mammalian target of rapamycin (mTOR), eukaryotic initiation factor 4E binding protein 1 (4E-BP1), and p70(s6kinase) in chronic complete SCI patients. |
| 622 | 19533653 | In SCI patients, when compared with controls, there was a significant reduction in mRNA levels of atrogin-1 (59%; P < 0.05), MuRF1 (55%; P < 0.05), and myostatin (46%; P < 0.01), and in protein levels of FoXO1 (72%; P < 0.05), FoXO3a (60%; P < 0.05), and atrogin-1 (36%; P < 0.05). |
| 623 | 19533653 | Decreases in the protein levels of IGF-1 (48%; P < 0.001) and phosphorylated GSK-3beta (54%; P < 0.05), 4E-BP1 (48%; P < 0.05), and p70(s6kinase) (60%; P = 0.1) were also observed, the latter three in an Akt- and mTOR-independent manner. |
| 624 | 19533653 | Reductions in atrogin-1, MuRF1, FoXO, and myostatin suggest the existence of an internal mechanism aimed at reducing further loss of muscle proteins during chronic SCI. |
| 625 | 19533653 | The downregulation of signaling proteins that regulate anabolism, such as IGF, GSK-3beta, and 4E-BP1, would reduce the ability to increase protein synthesis rates. |
| 626 | 19533653 | Atrogin-1, MuRF1, and FoXO, as well as phosphorylated GSK-3beta and 4E-BP1 are reduced in skeletal muscle of chronic spinal cord-injured patients. |
| 627 | 19533653 | Therefore, the aim of this study was to determine whether there was an increase in catabolic signaling targets, such as atrogin-1, muscle ring finger-1 (MuRF1), forkhead transcription factor (FoXO), and myostatin, and decreases in anabolic signaling targets, such as insulin-like growth factor (IGF), v-akt murine thymoma viral oncogene (Akt), glycogen synthase kinase-beta (GSK-3beta), mammalian target of rapamycin (mTOR), eukaryotic initiation factor 4E binding protein 1 (4E-BP1), and p70(s6kinase) in chronic complete SCI patients. |
| 628 | 19533653 | In SCI patients, when compared with controls, there was a significant reduction in mRNA levels of atrogin-1 (59%; P < 0.05), MuRF1 (55%; P < 0.05), and myostatin (46%; P < 0.01), and in protein levels of FoXO1 (72%; P < 0.05), FoXO3a (60%; P < 0.05), and atrogin-1 (36%; P < 0.05). |
| 629 | 19533653 | Decreases in the protein levels of IGF-1 (48%; P < 0.001) and phosphorylated GSK-3beta (54%; P < 0.05), 4E-BP1 (48%; P < 0.05), and p70(s6kinase) (60%; P = 0.1) were also observed, the latter three in an Akt- and mTOR-independent manner. |
| 630 | 19533653 | Reductions in atrogin-1, MuRF1, FoXO, and myostatin suggest the existence of an internal mechanism aimed at reducing further loss of muscle proteins during chronic SCI. |
| 631 | 19533653 | The downregulation of signaling proteins that regulate anabolism, such as IGF, GSK-3beta, and 4E-BP1, would reduce the ability to increase protein synthesis rates. |
| 632 | 19533653 | Atrogin-1, MuRF1, and FoXO, as well as phosphorylated GSK-3beta and 4E-BP1 are reduced in skeletal muscle of chronic spinal cord-injured patients. |
| 633 | 19533653 | Therefore, the aim of this study was to determine whether there was an increase in catabolic signaling targets, such as atrogin-1, muscle ring finger-1 (MuRF1), forkhead transcription factor (FoXO), and myostatin, and decreases in anabolic signaling targets, such as insulin-like growth factor (IGF), v-akt murine thymoma viral oncogene (Akt), glycogen synthase kinase-beta (GSK-3beta), mammalian target of rapamycin (mTOR), eukaryotic initiation factor 4E binding protein 1 (4E-BP1), and p70(s6kinase) in chronic complete SCI patients. |
| 634 | 19533653 | In SCI patients, when compared with controls, there was a significant reduction in mRNA levels of atrogin-1 (59%; P < 0.05), MuRF1 (55%; P < 0.05), and myostatin (46%; P < 0.01), and in protein levels of FoXO1 (72%; P < 0.05), FoXO3a (60%; P < 0.05), and atrogin-1 (36%; P < 0.05). |
| 635 | 19533653 | Decreases in the protein levels of IGF-1 (48%; P < 0.001) and phosphorylated GSK-3beta (54%; P < 0.05), 4E-BP1 (48%; P < 0.05), and p70(s6kinase) (60%; P = 0.1) were also observed, the latter three in an Akt- and mTOR-independent manner. |
| 636 | 19533653 | Reductions in atrogin-1, MuRF1, FoXO, and myostatin suggest the existence of an internal mechanism aimed at reducing further loss of muscle proteins during chronic SCI. |
| 637 | 19533653 | The downregulation of signaling proteins that regulate anabolism, such as IGF, GSK-3beta, and 4E-BP1, would reduce the ability to increase protein synthesis rates. |
| 638 | 19561140 | Short-term exposure to UCF-101 did not change the expression of X-linked inhibitor of apoptosis protein (XIAP) and Omi stress-regulated endoprotease, high temperature requirement protein A2 (Omi/HtrA2), favouring an apoptosis-independent mechanism. |
| 639 | 19561140 | In addition, UCF-101 promoted the phosphorylation of p38 mitogen-activated protein kinases and c-Jun N-terminal kinase (JNK) after 15 min of incubation, while it failed to affect the phosphorylation of extracellular signal-regulated kinase (ERK) and glycogen synthase kinase-3beta (GSK-3beta) within 120 min in H9C2 myoblasts. |
| 640 | 19616957 | The GSK-3beta inhibitory activity of PMHs entitles them to be potential leads for the treatment of cancer, Alzheimer's disease, bipolar disorders, stroke, different tau pathologies, and type-2 diabetes. |
| 641 | 19716700 | Palbinone and triterpenes from Moutan Cortex (Paeonia suffruticosa, Paeoniaceae) stimulate glucose uptake and glycogen synthesis via activation of AMPK in insulin-resistant human HepG2 Cells. |
| 642 | 19716700 | These compounds remakably stimulated AMP-activated protein kinase (AMPK), GSK-3beta, and ACC phosphorylation. |
| 643 | 19817973 | In addition, melatonin increased the phosphorylation of subcellular signals at the level of protein kinase C zeta (PKCzeta), Akt, and glycogen synthase kinase 3beta (GSK3beta) while the increase in glycogen synthesis induced by melatonin was inhibited by PKCzeta pseudo-peptide. |
| 644 | 20080974 | Glycogen synthase kinase-3 (GSK-3) isoforms, GSK-3alpha and GSK-3beta, are serine/threonine kinases involved in numerous cellular processes and diverse diseases, including Alzheimer disease, cancer, and diabetes. |
| 645 | 20080974 | Here, we describe a structure-function analysis of GSK-3alpha and GSK-3beta in mammalian cells. |
| 646 | 20080974 | We examined the effect of these mutations on GSK-3 activity toward Tau, activity in Wnt signaling, interaction with Axin, and GSK-3alpha/beta Tyr(279/216) phosphorylation. |
| 647 | 20080974 | Glycogen synthase kinase-3 (GSK-3) isoforms, GSK-3alpha and GSK-3beta, are serine/threonine kinases involved in numerous cellular processes and diverse diseases, including Alzheimer disease, cancer, and diabetes. |
| 648 | 20080974 | Here, we describe a structure-function analysis of GSK-3alpha and GSK-3beta in mammalian cells. |
| 649 | 20080974 | We examined the effect of these mutations on GSK-3 activity toward Tau, activity in Wnt signaling, interaction with Axin, and GSK-3alpha/beta Tyr(279/216) phosphorylation. |
| 650 | 20175116 | Further studies revealed that HG treatment resulted in phosphorylation and membrane translocation of Rac1, p47phox, and p67phox subunits leading to NADPH oxidase activation. |
| 651 | 20175116 | GSPs treatment remarkably disrupted the phosphorylation and membrane translocation of Rac1, p47phox, and p67phox subunits. |
| 652 | 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. |
| 653 | 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. |
| 654 | 20347724 | Diabetes induces changes in ILK, PINCH and components of related pathways in the spinal cord of rats. |
| 655 | 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. |
| 656 | 20347724 | ILK and PINCH proteins levels were significantly decreased and both colocalized to neurons and oligodendrocytes. |
| 657 | 20347724 | Phosphorylation of tau and MAP2A/B protein expression were significantly increased, and expression of synaptophysin and drebrin were reduced in diabetic rats. |
| 658 | 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. |
| 659 | 20357182 | Curcumin-induced suppression of adipogenic differentiation is accompanied by activation of Wnt/beta-catenin signaling. |
| 660 | 20357182 | Curcumin inhibited mitogen-activated protein kinase (MAPK) (ERK, JNK, and p38) phosphorylation that was associated with differentiation of 3T3-L1 cells into adipocytes. |
| 661 | 20357182 | During differentiation, curcumin also restored nuclear translocation of the integral Wnt signaling component beta-catenin in a dose-dependent manner. |
| 662 | 20357182 | In parallel, curcumin reduced differentiation-stimulated expression of CK1alpha, GSK-3beta, and Axin, components of the destruction complex targeting beta-catenin. |
| 663 | 20357182 | Accordingly, quantitative PCR analysis revealed that curcumin inhibited the mRNA expression of AP2 (mature adipocyte marker) and increased the mRNA expression of Wnt10b, Fz2 (Wnt direct receptor), and LRP5 (Wnt coreceptor). |
| 664 | 20357182 | Curcumin also increased mRNA levels of c-Myc and cyclin D1, well-known Wnt targets. |
| 665 | 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. |
| 666 | 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. |
| 667 | 20368287 | Moreover, GSK3 inhibitors increased DEAF1 transcriptional activity on the 5-HT1A serotonin receptor promoter. |
| 668 | 20398714 | Moreover, we found that diabetes further increased AT8, a marker of hyperphosphorylated tau, protein and immunopositive stained cells in the hippocampus of rats following MCAO while reduced the level of phosphorylated glycogen synthase kinase 3-beta at serine-9 residues (p-ser9-GSK-3beta), indicating activation of GSK-3beta. |
| 669 | 20398714 | We conclude that diabetes further deteriorates ischemia-induced brain damage and cognitive deficits which may be associated with abnormal phosphorylation of tau as well as activation of GSK-3beta. |
| 670 | 20398714 | Moreover, we found that diabetes further increased AT8, a marker of hyperphosphorylated tau, protein and immunopositive stained cells in the hippocampus of rats following MCAO while reduced the level of phosphorylated glycogen synthase kinase 3-beta at serine-9 residues (p-ser9-GSK-3beta), indicating activation of GSK-3beta. |
| 671 | 20398714 | We conclude that diabetes further deteriorates ischemia-induced brain damage and cognitive deficits which may be associated with abnormal phosphorylation of tau as well as activation of GSK-3beta. |
| 672 | 20404919 | RAGE modulates hypoxia/reoxygenation injury in adult murine cardiomyocytes via JNK and GSK-3beta signaling pathways. |
| 673 | 20466847 | Glycogen synthase kinase 3 beta mediates high glucose-induced ubiquitination and proteasome degradation of insulin receptor substrate 1. |
| 674 | 20466847 | Genetic and biological studies have shown that reductions in IRS1 and/or IRS2 protein levels are associated with insulin resistance. |
| 675 | 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. |
| 676 | 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. |
| 677 | 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. |
| 678 | 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. |
| 679 | 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. |
| 680 | 20466847 | Glycogen synthase kinase 3 beta mediates high glucose-induced ubiquitination and proteasome degradation of insulin receptor substrate 1. |
| 681 | 20466847 | Genetic and biological studies have shown that reductions in IRS1 and/or IRS2 protein levels are associated with insulin resistance. |
| 682 | 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. |
| 683 | 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. |
| 684 | 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. |
| 685 | 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. |
| 686 | 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. |
| 687 | 20554184 | Quantitative real-time PCR was used to investigate CE effects on the expression of genes coding for adipokines, glucose transporter (GLUT) family, and insulin-signaling components in mouse 3T3-L1 adipocytes. |
| 688 | 20554184 | CE decreased the expression of further genes encoding insulin-signaling pathway proteins including GSK3B, IGF1R, IGF2R, and PIK3R1. |
| 689 | 21910999 | As a result, five shared risk feature genes, CD80, EGFR, FN1, GSK3B and TRAF6 were found and proven to be associated with rheumatoid arthritis by previous reports. |
| 690 | 23832395 | We found that STZ-induced diabetes resulted in decreased hippocampal expression of genes involved in epigenetic regulation and synaptic plasticity, for example, histone deacetylases and glycogen synthase kinase 3 beta (HDACs and GSK3β). |
| 691 | 23832395 | We also found increased expression of genes involved in signalling cascades related to cell growth, cell survival and energy metabolism, such as neurotropic tyrosine kinase receptor type 2, apolipoprotein E, and protein tyrosine phosphatase receptor type (Ntrk2, APOE, PTPRT). |
| 692 | 23904355 | We used the 3.6-kb Col1a1 promoter to inactivate the Gsk3b gene (Col1a1-Gsk3b knockout) in skeletal cells. |