- About
- Home
- Introduction
- Statistics
- Programs
- Dignet
- Gene
- GenePair
- Help & Docs
- Documents
- Help
- FAQs
- Links
- Acknowledge
- Disclaimer
- Contact Us
Gene Information
Gene symbol: AKT1
Gene name: v-akt murine thymoma viral oncogene homolog 1
HGNC ID: 391
Synonyms: RAC, PKB, PRKBA, AKT
Related Genes
Related Sentences
| # | PMID | Sentence |
| 1 | 21896669 | Western blotting was used to quantify the expression and phosphorylation of insulin receptor, insulin receptor substrate 1, and Akt and of inflammatory mediators that modulate insulin signaling in a negative manner (IKK?, JNK, and inducible nitric oxide synthase). |
| 2 | 22031698 | Here we describe that targeting Akt kinase to the cell membrane markedly reduced sensitivity of phosphorylated Akt to dephosphorylation by protein phosphatase 2A. |
| 3 | 21272185 | Western blot analysis revealed that the effects of comparable Akt phosphorylation, reduced AMPK phosphorylation, downregulation of sarco(endo)plasmic reticulum Ca(2+)-ATPase and lessened phosphorylation of phospholamban in diabetic myocardium were unaffected by apocynin. |
| 4 | 21437903 | Insulin treatment (10 mU/ml/30 min) increased the phosphorylation of the IR ?-subunit and Akt. |
| 5 | 21143387 | In cardiomyocytes, CM from EAT of HFD-fed animals increased SMAD2-phosphorylation, a marker for activin A-signalling, decreased sarcoplasmic-endoplasmic reticulum calcium ATPase 2a expression, and reduced insulin-mediated phosphorylation of Akt-Ser473 versus CM from SAT and standard diet-fed animals. |
| 6 | 21926268 | At the molecular level, insulin-elicited activation of protein kinase B (Akt) and endothelial NO synthase and production of NO were enhanced in APPL1 transgenic mice but were abrogated in APPL1 knockout mice. |
| 7 | 21926268 | In endothelial cells, APPL1 potentiated insulin-stimulated Akt activation by competing with the Akt inhibitor Tribbles 3 (TRB3) and suppressed ERK1/2 signaling by altering the phosphorylation status of its upstream kinase Raf-1. |
| 8 | 21933986 | In contrast, inhibition of phosphatidylinositol 3-kinase (PI3K) or PKB significantly increased IRS-2 levels in ?-cells. |
| 9 | 21933987 | Furthermore, with TRB3 gene silencing, the inhibited phosphorylation of Akt was restored and the increased phosphorylation of extracellular signal-regulated kinase 1/2 and Jun NH(2)-terminal kinase in DCM was significantly decreased. |
| 10 | 21801810 | Additionally we investigated the effect of NPY on insulin action in adipocyte cultures by assessing the phosphorylation of Akt and [(3)H]-deoxyglucose uptake. |
| 11 | 21914810 | In the presence of Rheb and insulin, PRAS40 release is abolished by Akt inhibition without diminishing mTORC1 signaling. |
| 12 | 9392506 | In soleus muscle from GK rats, maximal insulin-stimulated (120 nmol/l) Akt kinase activity was reduced by 68% (P < 0.01) and glucose transport was decreased by 39% (P < 0.05), compared with Wistar rats. |
| 13 | 9392506 | At a submaximal insulin concentration (2.4 nmol/l), activity of Akt kinase and glucose transport were unaltered. |
| 14 | 9392506 | In conclusion, improved glucose tolerance in diabetic GK rats by phlorizin treatment fully restored insulin-stimulated activity of Akt kinase and glucose transport. |
| 15 | 10811851 | Protein kinase B (PKB) activity in liver was decreased in null mice compared with the wild-type and the null mice expressing IRS-1 or IRS-1Deltap85. |
| 16 | 10811851 | These data suggest that PKB in liver plays a pivotal role in systemic glucose homeostasis and that PKB activation might be sufficient for reducing insulin resistance even without full activation of PI3K. |
| 17 | 10749857 | Similarly, in adipocytes of nondiabetic rats, rosiglitazone provoked increases in insulin-stimulated 2-deoxyglucose uptake, PKC-zeta/lambda enzyme activity and phosphorylation of both threonine 410 activation loop and threonine 560 autophosphorylation sites in PKC-zeta, but had no effect on PI 3-kinase activation or PKB activation/phosphorylation. |
| 18 | 11018037 | Furthermore, overexpression of constitutive active Akt was sufficient to induce CTGF gene expression, and inhibition of Akt activation by overexpressing dominant negative mutant of Akt abolished the VEGF-induced CTGF expression. |
| 19 | 10861205 | Thus acute activation of PKB is sufficient to induce SREBP1 mRNA accumulation in primary hepatocytes, and might be the major signalling event by which insulin induces SREBP1 gene expression in the liver. |
| 20 | 11147784 | IGF-I promotes the survival of multiple cell types by activating the IGF-I receptor (IGF-IR), which signals downstream to a serine/threonine kinase termed Akt. |
| 21 | 11274905 | At LG, insulin stimulated PKB activity. |
| 22 | 11274905 | Again, both HG and GlcN significantly reduced insulin's ability to stimulate PKB activity. |
| 23 | 11274905 | We conclude that the hexosamine-mediated insulin resistance of GS activity seen in rat-1 cells is mediated by hexosamine regulation of PI-3K and PKB. |
| 24 | 11124266 | We show that in mammalian cells, C. elegans DAF-16 is a direct target of AKT and that AKT phosphorylation generates 14-3-3 binding sites and regulates the nuclear/cytoplasmic distribution of DAF-16 as previously shown for its mammalian homologs FKHR and FKHRL1. |
| 25 | 11342531 | SOCS-1 and SOCS-6 do not inhibit insulin-dependent IR autophosphorylation, but both proteins inhibit insulin-dependent activation of ERK1/2 and protein kinase B in vivo and IR-directed phosphorylation of IRS-1 in vitro. |
| 26 | 11402048 | However, cells expressing the eNOS-S1179A mutant (disrupted Akt phosphorylation site) did not produce detectable NO in response to insulin, whereas the response to LPA was similar to that observed in cells expressing wild-type eNOS. |
| 27 | 11402048 | We conclude that insulin regulates eNOS activity using a Ca(2+)-independent mechanism requiring phosphorylation of eNOS by Akt. |
| 28 | 11560942 | Exposure of R28 cells, a model of retinal neurons, to 20 mm glucose for 24 h attenuated the ability of 10 nm insulin to rescue them from serum deprivation-induced apoptosis and to phosphorylate Akt compared with 5 mm glucose. |
| 29 | 11560942 | Azaserine, a glutamine:fructose-6-phosphate amidotransferase inhibitor, reversed the effect of 20 mm glucose, but not that of 1.5 mm glucosamine, on attenuation of the ability of insulin to promote cell survival and phosphorylate Akt as well as accumulation of UDP-HexNAc. |
| 30 | 11560942 | These results suggest that the excessive glucose flux through the HBP may direct retinal neurons to undergo apoptosis in a bimodal fashion; i.e. via perturbation of the neuroprotective effect of insulin mediated by Akt and via induction of apoptosis possibly by altered glycosylation of proteins. |
| 31 | 11739095 | There was also no change in insulin-stimulated protein kinase B activity (1.3 +/- 0.1 vs. 1.4 +/- 0.2-fold stimulation with insulin) with training. |
| 32 | 11812753 | Insulin-stimulated Akt activity also increased after troglitazone treatment (from 32 +/- 8 to 107 +/- 32% stimulation, P < 0.05) but was unchanged after metformin therapy. |
| 33 | 11916914 | Phosphorylation of p70(S6K) was also increased by IGF-1/glucose, but not by TGF-alpha/EGF, despite upstream PKB activation. |
| 34 | 11916922 | Transfection of cells in culture with ASO targeting PTEN reduced PTEN mRNA and protein levels and increased insulin-stimulated Akt phosphorylation in alpha-mouse liver-12 (AML12) cells. |
| 35 | 11916922 | Inhibition of PTEN expression also dramatically reduced insulin concentrations in ob/ob mice, improved the performance of db/db mice during insulin tolerance tests, and increased Akt phosphorylation in liver in response to insulin. |
| 36 | 11922615 | In vitro phosphorylation analyses revealed that shikonin did not induce tyrosine phosphorylation of the insulin receptor, but significantly induced both Thr-308 and Ser-473 phosphorylation of Akt. |
| 37 | 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. |
| 38 | 11991199 | PDGF also stimulated phosphorylation of protein kinase B (Akt/PKB) and p70 S6Kinase (p70S6K) in a wortmannin-sensitive manner. |
| 39 | 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. |
| 40 | 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. |
| 41 | 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. |
| 42 | 12101188 | This effect of SAP-1 was dependent on cellular caspase activities and was preceded by inactivation of two serine-threonine protein kinases, Akt and integrin-linked kinase (ILK), both of which function downstream of phosphoinositide (PI) 3-kinase to promote cell survival. |
| 43 | 12101188 | Furthermore, expression of a dominant negative mutant of PI 3-kinase did not induce cell death as efficiently as did SAP-1, although this mutant inhibited Akt and ILK activities more effectively than did SAP-1. |
| 44 | 12101188 | These results suggest that SAP-1 induces apoptotic cell death by at least two distinct mechanisms: inhibition of cell survival signaling mediated by PI 3-kinase, Akt, and ILK and activation of a caspase-dependent proapoptotic pathway. |
| 45 | 12424252 | In order to investigate the effects of CNTF on fat cells, we examined the expression of CNTF receptor complex proteins (LIFR, gp130, and CNTFRalpha) during adipocyte differentiation and the effects of CNTF on STAT, Akt, and MAPK activation. |
| 46 | 12560330 | Ectopically expressed SOCS-3 associated with the IR and suppressed insulin-dependent receptor autophosphorylation, insulin receptor substrate-1 (IRS-1) tyrosine phosphorylation, association of IRS-1 with the p85 subunit of phosphatidylinositol 3-kinase, and activation of Akt. |
| 47 | 12663464 | It is unknown, however, which Akt isoform shows impaired activation in insulin resistance. |
| 48 | 12663464 | Hence, we investigated the stimulation of PI3K and Akt-1, -2, and -3 by insulin and epidermal growth factors (EGFs) in skeletal muscles from lean and obese insulin-resistant humans. |
| 49 | 12663464 | Insulin activated all Akt isoforms in lean muscles, whereas only Akt-1 was activated in obese muscles. |
| 50 | 12663464 | Insulin receptor substrate (IRS)-1 was associated with PI3K activity, which is necessary for Akt activation by insulin, and was reduced in obese muscles, and this was accompanied by decreased IRS-1 expression. |
| 51 | 12594228 | Suppression of IRS-1/2 down-regulation by LY294002 rescued the responsiveness of PKB and MAPK toward acute insulin stimulation. |
| 52 | 12594228 | IRS-2 appears to be the chief molecule responsible for MAPK and PKB activation by insulin, as knockdown of IRS-2 (but not IRS-1) by RNA interference severely impaired activation of both kinases. |
| 53 | 12594228 | In summary, (i) PI3K mediates insulin-induced reduction of IRS-1 by phosphorylating it while a PI3K/mTOR pathway controls insulin-induced reduction of IRS-2, (ii) in L6 cells, IRS-2 is the major adapter molecule linking the insulin receptor to activation of PKB and MAPK, (iii) the mechanism of IRS-1/2 down-regulation is different in L6 cells compared with 3T3-L1 adipocytes. |
| 54 | 12714600 | Furthermore, other serine kinases including Akt, extracellular regulated kinase, mammalian target of rapamycin, and PKCzeta were also activated by TNF-alpha (as assessed by phospho-specific antibodies). |
| 55 | 12825835 | The antiapoptotic protein, Akt, was not affected by P2Y6 receptor activation. |
| 56 | 12941762 | Downstream PI 3-kinase, activation of Akt, glycogen synthase kinase (GSK)-3 (alpha and beta isoforms), Foxo1, and atypical protein kinase C were blunted in insulin-stimulated IRS-2(-/-) cells. |
| 57 | 12837666 | However, stretch had no effect on Akt in the slow-twitch soleus muscle, although there was a robust phosphorylation of the stress-activated protein kinase p38. |
| 58 | 12909611 | Exercise synergistically enhanced insulin-stimulated insulin receptor substrate 1-associated phosphatidylinositol 3-kinase activity (P < 0.05) and Akt Ser473 phosphorylation (P < 0.05) in nondiabetic subjects but had little effect in diabetic subjects. |
| 59 | 12941959 | Using transgenic mice expressing activated calcineurin in skeletal muscle, we report that skeletal muscle reprogramming by calcineurin activation leads to improved insulin-stimulated 2-deoxyglucose uptake in extensor digitorum longus (EDL) muscles compared with wild-type mice, concomitant with increased protein expression of the insulin receptor, Akt, glucose transporter 4, and peroxisome proliferator-activated receptor-gamma co-activator 1. |
| 60 | 12944390 | Using phospho-specific antibodies, we observed that either adiponectin or insulin treatment (but not LPA treatment) caused phosphorylation of both Akt at Ser473 and endothelial nitric-oxide synthase (eNOS) at Ser1179 that was inhibitable by wortmannin. |
| 61 | 14500580 | The activity of FOXO proteins is principally regulated by activation of protein kinase B (PKB)/Akt by insulin and other cytokines. |
| 62 | 14504291 | These cells have a 50% decrease in PI 3-kinase activity and a 30% decrease in Akt activity, leading to decreased insulin-induced glucose uptake and anti-apoptosis. |
| 63 | 14504291 | Pik3r2-/- (p85 beta-/-) cells show a 25% reduction of p85 protein but normal levels of p85-p110 and PI 3-kinase activity, supporting the fact that p85 is more abundant than p110 in wild type. p85 beta-/- cells, however, exhibit significantly increased insulin-induced Akt activation, leading to increased anti-apoptosis. |
| 64 | 14504291 | Reconstitution experiments suggest that the discrepancy between PI 3-kinase activity and Akt activity is at least in part due to the p85-dependent negative regulation of downstream signaling of PI 3-kinase. |
| 65 | 14505487 | Previous work showed that acute stimulation of a conditionally active protein kinase B (PKB or cAKT) was sufficient to elicit insulin-like induction of GCK (glucokinase) and SREBP1 (sterol regulatory element-binding protein 1) in hepatocytes [Iynedjian, Roth, Fleischmann and Gjinovci (2000) Biochem. |
| 66 | 14505487 | The stimulation of gene expression by constitutively active PKB-CaaX and inhibition of the insulin effect by ceramide are compatible with a role for PKB in the insulin-dependent induction of GCK and SREBP1. |
| 67 | 15044356 | The proliferative effects of GLP-1 appear to involve multiple intracellular pathways, including stimulation of Akt, activation of protein kinase Czeta, and transactivation of the epidermal growth factor receptor through the c-src kinase. |
| 68 | 15044356 | GLP-1 receptor activation also promotes cell survival in beta-cells and neurons via increased levels of cAMP leading to cAMP response element binding protein activation, enhanced insulin receptor substrate-2 activity and, ultimately, activation of Akt. |
| 69 | 15143198 | Furthermore, in vivo insulin-induced activation of the protein kinase Akt is enhanced in skeletal muscle and liver from mice lacking phosphatidylinositol 5-phosphate 4-kinase beta. |
| 70 | 15010337 | Although a pharmacological dose of insulin produces a dramatic increase in phosphorylation and activity of Akt isoforms 1 and 2 in mammalian skeletal muscle, few studies have examined the effect of physiological concentrations of insulin on the phosphorylation of Akt-1 and -2 in normal and diabetic tissue. |
| 71 | 15211372 | The IKK inhibitor I229 did not affect protein expression of Akt, but fully restored insulin action in myocytes subjected to co-culture. |
| 72 | 15240629 | Protein kinase B (PKB) expression and phosphorylated PKB levels in response to insulin stimulation (20 nm) were comparable in the diabetic and control cultures. 5-Amino-4-imidazolecarboxamide riboside (AICAR) mimics the effect of exercise on glucose uptake by activating AMP-activated protein kinase. |
| 73 | 15467831 | Reduction of Akt activity in transgenic animals resulted in impaired glucose tolerance due to defective insulin secretion. |
| 74 | 15339744 | Yet unknown mechanisms in insulin signaling downstream of Akt may be responsible. |
| 75 | 15526284 | High glucose can trigger endothelial cell apoptosis by de-activation of endothelial nitric oxide synthase (eNOS). eNOS was recently demonstrated to be extensively regulated by Akt and heat shock protein 90 (HSP90). |
| 76 | 15590659 | These data suggest that insulin inhibits glucagon gene transcription by signaling via PI 3-kinase and PKB, with the transcription factor Pax6 and its potential coactivator CBP being critical components of the targeted promoter-specific nucleoprotein complex. |
| 77 | 15386812 | Signaling-related defects in the soleus muscle of sedentary obese Zucker rats, which impaired glucose transporter subtype 4 (GLUT 4), included decreased phosphorylation of insulin receptor substrate (IRS)-1, as well as an attenuated p85 regulatory subunit of phosphatidylinositol 3-kinase (PI3 kinase) and Akt serine phosphorylation. |
| 78 | 15632103 | Insulin increased the phosphorylation of Akt in all cardiomyocyte preparations (control, db/db, COOH-treated db/db) to the same extent. |
| 79 | 15632103 | Thus insulin has selective metabolic actions in mouse cardiomyocytes; deoxyglucose uptake and Akt phosphorylation are increased, but fatty acid oxidation and AMPK phosphorylation are unchanged. |
| 80 | 15935144 | The three principal objectives of this commentary are to: (i) review the existing evidence, which suggests regulation, by glucose and other insulin secretagogues, of PP2A in the beta cell; (ii) discuss the experimental evidence, which implicates PP2A-like enzymes in the dephosphorylation and inactivation of key beta cell phosphoprotein substrates (e.g., Akt and Bcl-2), which may be necessary for beta cell proliferation and survival, culminating in the loss of the beta cell mass; and (iii) highlight potential avenues for future research, including the development of specific pharmacological and therapeutic interventional modalities for the inhibition of specific PP2A-like phosphatases for the prevention of loss of beta cell mass leading to the onset of diabetes. |
| 81 | 15935983 | Under serum-free conditions, recombinant human IGFBP-3 blocked Akt phosphorylation at threonine 308 (pThr308), whereas anti-sense oligo treatment was associated with enhanced pThr308 activity. |
| 82 | 15855265 | In mice, a heterozygous deletion of the Pten gene is associated with increased activation of AKT and with development of pheochromocytomas. |
| 83 | 16061670 | The present study shows that PTEN can partially inhibit the Wnt-1-induced mammary tumorigenesis in early neoplastic stages by blocking the AKT pathway and by reducing the IGF-I receptor levels in mammary gland. |
| 84 | 16087719 | We have investigated, in isolated rat adipocytes, the changes caused by GLP-1, Ex-4 and Ex-9 compared with those provoked by insulin or glucagon, upon the activity of phosphatidylinositol-3-kinase (PI3K), protein kinase B (PKB), p42/44 MAP kinases (MAPKs) and p70s6 kinase (p70s6k), and the participation of these kinases and protein kinase C (PKC) in their action upon 2-deoxy-d-glucose uptake, lipolysis and lipogenesis. |
| 85 | 16087719 | In normal rat adipocytes, GLP-1 and both exendins share with insulin an increasing action upon the activity of all kinases studied (except PKB), PI3K, p44 and p42 MAPKs and possibly PKC, all being required for their stimulating effect upon glucose uptake. |
| 86 | 16179727 | Insulin regulates glucose transport by activating insulin receptor substrate-1 (IRS-1)-dependent phosphatidylinositol 3-kinase (PI3K) which, via increases in PI-3,4,5-triphosphate (PIP(3)), activates atypical protein kinase C (aPKC) and protein kinase B (PKB/Akt). |
| 87 | 16179727 | In most cases, defective muscle aPKC/PKB activation reflects both impaired activation of IRS-1/PI3K, the upstream activator of aPKC and PKB in muscle and, in the case of aPKC, poor responsiveness to PIP(3), the lipid product of PI3K. |
| 88 | 16180585 | We have examined the basal and insulin-mediated phosphorylation of protein kinase B (PKB), protein kinase Czeta (PKCzeta), p70(S6k), mitogen-activated protein kinase (MAPK)/p90(rsk) pathway and the expression of IGFBP-3, -4, and -5 in mice selected for body weight gain (line C) and reduction (line L). |
| 89 | 16150913 | Interestingly, phosphorylation of IRS-1 at Tyr895 continued to increase over the 20-min period, and protein kinase B (PKB) phosphorylation at Ser473 reached a plateau by 5 min, demonstrating that different profiles of phosphorylation are involved in transmission of the insulin signal despite a constant level of insulin stimulation. |
| 90 | 16150913 | These results demonstrate that under conditions of increased insulin, similar to those used to assess insulin action in vivo, chronic high-fat feeding impairs insulin signal transduction related to glucose metabolism at the level of IRS-1 Tyr612 and PKB Ser473 and that these effects are independent of the type of fat used in the high-fat diet. |
| 91 | 16170201 | The Irs2 branch of the insulin/insulin-like growth factor signaling cascade activates the phosphatidylinositol 3-kinase --> Akt --> Foxo1 cascade in many tissues, including hepatocytes and pancreatic beta-cells. |
| 92 | 16170201 | Pten insufficiency increased peripheral insulin sensitivity in wild type and Irs2(-/-) mice and increased Akt and Foxo1 phosphorylation in the islets. |
| 93 | 16311104 | Glucose transport, insulin receptor (IR), and IR substrate 1 (IRS1) phosphorylation, phosphatidylinositol 3'-kinase (PI3K) activity, as well as Akt-Ser473 phosphorylation have been investigated at the end of the incubation period and after a further short-term insulin stimulation. |
| 94 | 16311104 | After a short-term insulin stimulation (10 nmol/L insulin for 10 minutes), IR and IRS1 tyrosine phosphorylation, PI3K activation, and Akt-Ser473 phosphorylation significantly increased (P < .01 and P < .05 for Akt) in SkMC-L but not in SkMC-H. |
| 95 | 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. |
| 96 | 16186174 | Finally, using in vitro cellular models of amyloid precursor protein (APP)-processing and Abeta generation/clearance, we confirmed that human recombinant (hr)CTGF may increase Abeta1-40 and Abeta1-42 peptide steady-state levels, possibly through a mechanism that involves gamma-secretase activation and decreased insulin-degrading enzyme (IDE) steady-state levels in a MAP kinase (MAPK)/ phosphatidylinositol 3-kinase (PI-3K)/protein kinase-B (AKT)1-dependent manner. |
| 97 | 16557003 | The PI3-K pathway, which activates serine/threonine protein kinase Akt, enhances NO synthase phosphorylation and NO production. |
| 98 | 16216433 | NADPH oxidase-derived reactive oxygen species (ROS) generation is required for the AGE-RAGE signaling in vascular wall cells, and small G protein Rac is a critical component of vascular NADPH oxidase complex. |
| 99 | 16344371 | Akt activity was increased by Ang II and returned to basal levels under rosiglitazone in both vascular beds. |
| 100 | 16399506 | Conversely, increased PI3K signaling induced by hypothalamic overexpression of either IRS-2 or protein kinase B (PKB, a key downstream mediator of PI3K action) enhanced the glycemic response to insulin by approximately 2-fold in STZ-DM rats. |
| 101 | 16234413 | In endothelial cells, S1P has been shown to modulate the activity of the endothelial nitric-oxide synthase (eNOS) through phosphorylation operated by Akt. |
| 102 | 16339499 | Using Ser473 phosphorylation of protein kinase B as output for insulin signaling, a 2-fold increase is found in insulin-stimulated normal platelets, but in DM platelets there is no significant response. |
| 103 | 16341839 | We used a conditionally active form of PKB, produced using recombinant adenovirus, to test the role of acute PKB activation in the control of glycogen phosphorylase and glycogen synthesis in hepatocytes. |
| 104 | 16341839 | Glycogen synthesis correlated inversely with the activity of phosphorylase-a, irrespective of whether this was modulated by insulin, by PKB activation or by a selective phosphorylase ligand, supporting an essential role for phosphorylase inactivation in the glycogenic action of insulin in hepatocytes. |
| 105 | 16375864 | In the present study, we found that Akt down-regulation is important for inducing CHOP expression, an ER stress-induced transcription factor. |
| 106 | 16424109 | Unlike insulin, the PI3-K inhibitor wortmannin did not reverse GE antilipolysis, and GE did not affect phosphorylation of protein kinase B (PKB). |
| 107 | 16505232 | Insulin-stimulated increases in Akt phosphorylation and cGMP concentration (a measure of NO bioavailability) after euglycemic-hyperinsulinemic clamp were blunted in the aorta of fatty compared with lean rats but were partly normalized after 2 weeks of treatment with the PKCbeta inhibitor ruboxistaurin (LY333531). |
| 108 | 16505232 | In endothelial cell culture, overexpression of PKCbeta1 and -beta2, but not PKCalpha, -delta, or -zeta, decreased insulin-stimulated Akt phosphorylation and eNOS expression. |
| 109 | 16505232 | Overexpression of PKCbeta1 and -beta2, but not PKCalpha or -delta, also decreased Akt phosphorylation stimulated by vascular endothelial growth factor (VEGF). |
| 110 | 16505232 | In microvessels isolated from transgenic mice overexpressing PKCbeta2 only in vascular cells, Akt phosphorylation stimulated by insulin was decreased compared with wild-type mice. |
| 111 | 16505232 | Thus, activation of PKCbeta in endothelial cells and vascular tissue inhibits Akt activation by insulin and VEGF, inhibits Akt-dependent eNOS regulation by insulin, and causes endothelial dysfunction in obesity-associated insulin resistance. |
| 112 | 16506055 | It is also reduced in Zucker fa/fa rats, which present an impaired ability of insulin to induce Akt, ERK-1/2 and JNK-1/2 phosphorylation. |
| 113 | 16807405 | A marked decrease of basal and insulin-stimulated AKT phosphorylation, which correlated with the increase of patients' insulin resistance, and a significant increase of IRS total protein expression, together with a lower (IRS-2) or absent (IRS-1) increase of insulin-induced tyrosine phosphorylation, were found. |
| 114 | 16873695 | In the present study, we examined whether insulin's effect on PDK4 expression is impaired in acute insulin-resistant states and, if so, whether this change is accompanied by decreased insulin's effects to stimulate Akt and forkhead box class O (FOXO) 1 phosphorylation. |
| 115 | 16873695 | Insulin stimulation of Akt and FOXO1 phosphorylation was also significantly decreased with Intralipid and lactate infusions. |
| 116 | 16873703 | Our results suggest that PI3 kinase-dependent Akt activation, an essential signal for HSP72 expression, is depressed in the heart in insulin-resistant OLETF rats, and the results suggest also that the restoration of HSP72 expression and tolerance against ischemia/reperfusion injury by treatment with pioglitazone might be due to an improvement of insulin resistance, leading to restoration of impaired PI3 kinase-dependent Akt activation in response to hyperthermia. |
| 117 | 16880400 | Although PI3K enzymatic activity is diminished in L-Pik3r1KO livers because of a reduced level of regulatory and catalytic subunits of PI3K, insulin-stimulated Akt activity is actually increased. |
| 118 | 16880201 | The RabGAP (Rab GTPase-activating protein) AS160 (Akt substrate of 160 kDa) is a direct substrate of Akt and plays an essential role in the regulation of GLUT4 trafficking. |
| 119 | 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. |
| 120 | 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. |
| 121 | 16955284 | The aims of this study were to determine effects of diabetes duration on myocardial ischemia/reperfusion (I/R) injury and test whether time-dependent differences in sensitivity of the streptozotocin diabetic rat heart to I/R are related to differences in vascular density, levels of vascular endothelial growth factor (VEGF) or endothelial nitric oxide synthase (eNOS) expression, NO formation, activation of Akt, and/or oxidative stress. |
| 122 | 16842857 | Overexpression of PTEN and SKIP also inhibited insulin-induced phosphorylation of Akt and the uptake of glucose in cultured cells. |
| 123 | 16966378 | LKB1-mediated TRB3 expression provides a novel link between LKB1 and Akt, critical kinases involved in both tumor genesis and cell metabolism. |
| 124 | 17046573 | We found that the addition of either Ins or IGF-1 to BMMCs triggers the phosphorylation of protein kinase B (PKB) and p38 kinase but not extracellular signal-regulated kinase (Erk). |
| 125 | 16855220 | Corroborating these results, constitutively active Akt upregulated the signaling molecules involved in insulin-induced relaxation such as iNOS, cGK1alpha, and MBP activity, even in the absence of insulin stimulation. |
| 126 | 16855220 | On the contrary, the contractile response involving the phosphorylation of MYPT1 and MLC20, and increased ROKalpha activity stimulated by ANG II were all abolished by overexpressing active Akt. |
| 127 | 16855220 | In conclusion, we demonstrated here that insulin-induced VSMC relaxation is dependent on Akt activation via iNOS, cGK1alpha, and MBP activation, as well as the decreased phosphorylations of MYPT1 and MLC20 and decreased ROKalpha activity. |
| 128 | 17019595 | Insulin activation of (1) IRS1, (2) IRS2, (3) phosphotyrosine-associated phosphatidylinositol-3 kinase activity and (4) the substrate of phosphorylated Akt, AS160, a functional Rab GTPase activating protein important for GLUT4 (now known as solute carrier family 2 [facilitated glucose transporter], member 4 [SLC2A4]) translocation, was unchanged after acute or chronic exercise in either group. |
| 129 | 17028898 | The aim of this study was to test the hypothesis that dose-related effects of insulin may account for the reported differences in insulin signalling to PKB in diabetic muscle. |
| 130 | 17028898 | We compared enzymatic activation of aPKC and PKB, and PKB phosphorylation (threonine-308 and serine-473) during hyperinsulinaemic-euglycaemic clamp studies using both submaximal (400-500 pmol/l) and maximal (1400 pmol/l) insulin levels in non-diabetic control and obese diabetic subjects. |
| 131 | 17028898 | In lean control subjects, the submaximal insulin concentration increased aPKC activity and glucose disposal to approximately 50% of the maximal level and PKBbeta activity to 25% of the maximal level, but PKBalpha activity was not increased. |
| 132 | 17028898 | In obese diabetic subjects, whereas aPKC activation was defective at submaximal and maximal insulin concentrations, PKBbeta activation and the phosphorylation of PKBbeta and PKBalpha were defective at submaximal, but not maximal, insulin concentrations. |
| 133 | 17109620 | Inhibitors of insulin receptor tyrosine kinase, PI3K, Akt and mTOR abrogated insulin-induced Nrf2-mediated GCLc expression, redox balance, and IHEC survival. |
| 134 | 16962100 | Akt, mammalian target of rapamycin (mTOR), ribosomal-S6 kinase (p70(S6K)), the eukaryotic translation initiation factor 4E (eIF4E)-binding protein 1 (4E-BP1) and insulin receptor substrate (IRS)-2 were evaluated by Western blot analysis. |
| 135 | 16962100 | Acetaldehyde suppressed basal and insulin-stimulated Akt phosphorylation without affecting total Akt expression. |
| 136 | 16962100 | Rapamycin, which inhibits mTOR leading to inactivation of p70(S6K), did not affect acetaldehyde-induced inhibition on phosphorylation of Akt and mTOR. |
| 137 | 17063460 | While the early actions of FGF-21 on 3T3-L1 adipocytes involve rapid accumulation of intracellular calcium and phosphorylation of Akt, GSK-3, p70(S6K), SHP-2, MEK1/2, and Stat3, continuous treatment for 72 h induces an increase in PPARgamma protein expression. |
| 138 | 17182546 | Syk is constitutively activated in primary tumors and B lymphoma cell lines and curcumin down-modulates Syk activity accompanied by down-regulation of Akt activation. |
| 139 | 16960657 | We have already shown that chronic exposure to the ketone body beta-hydroxybutyrate (OHB) decreases insulin-mediated activation of protein kinase B (PKB) and glucose uptake in cardiomyocytes. |
| 140 | 17106060 | Moreover, ghrelin stimulated increased phosphorylation of Akt (Ser473) and eNOS (Akt phosphorylation site Ser1179) that was inhibitable by knockdown of GHSR-1a using siRNA or by pretreatment of cells with wortmannin but not with PD-98059. |
| 141 | 17218436 | We gave insulin intravenously to these rats and determined the association of glucose transporter-4 with plasma membranes, as well as the phosphorylation of phosphoinositide-dependent protein kinase-1 (PDK1), Akt, and PKCzeta. |
| 142 | 17218436 | Insulin stimulation of PDK1, Akt, and PKCzeta phosphorylation was also reduced. |
| 143 | 17287469 | The objective of this study was to determine whether CaMKKalpha regulates skeletal muscle glucose uptake, and whether it is dependent on AMPK and/or Akt activation. |
| 144 | 17287469 | Akt (Thr(308)) phosphorylation was not altered by CaMKKalpha, and caCaMKKalpha plus insulin stimulation did not increase the insulin-induced phosphorylation of Akt (Thr(308)). |
| 145 | 17287469 | Collectively, these results implicate CaMKKalpha in the regulation of skeletal muscle glucose uptake independent of AMPK and Akt activation. |
| 146 | 17303803 | These data demonstrate that deletion of Trib3 has minimal effect on insulin-induced Akt activation in hepatic tissue, and, as such, they question any nonredundant role for Trb3 in the maintenance of glucose and energy homeostasis in mice. |
| 147 | 17359956 | Finally, in db/db mice, considerable increases in phosphorylation of Akt on serine 473 and of eNOS on serine 1177 were found in aortas pretreated with apelin. |
| 148 | 17359956 | Apelin treatment modulates the abnormal aortic vascular tone in response to Ang II and acetylcholine by potentiating phosphorylation of Akt and eNOS in diabetic mice, suggesting that the apelin-APJ system might be an important regulator of vascular function in diabetes. |
| 149 | 17508911 | Increased levels of HO-1 produced a new pancreatic phenotype, as reflected by increases in phosphorylated AKT, BcL-xL and RSK levels, and decreases in O(2)- and 3-NT levels. |
| 150 | 17473225 | Phosphorylation of Akt was analyzed by Western blot and apoptosis by Blc-2 and Bax measurements. |
| 151 | 17599861 | Insulin-activated signaling pathways and pattern of Akt-1 and Akt-2 expression and insulin-stimulated phosphorylation were analyzed in skeletal muscle biopsy specimens. |
| 152 | 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). |
| 153 | 17513706 | AICAR significantly increased phosphorylation of extracellular signal-regulated kinase 1/2, but phosphorylation of beta-acetyl-CoA carboxylase, glycogen synthase, and protein kinase B or insulin receptor substrate-1 level was unchanged. |
| 154 | 17533199 | Further, there was reduced insulin induced Akt activation and increased tumor necrosis factor-alpha levels in vascular smooth muscle cells from Ren2 and Sprague-Dawley rats treated with angiotensin II, abnormalities that were abrogated by angiotensin type 1 receptor blockade with valsartan or antioxidant N-acetylcysteine. |
| 155 | 17550900 | At the molecular level, JNK1 knockdown mice had sustained and significant increase of hepatic Akt phosphorylation. |
| 156 | 17572128 | In contrast, decreased suppression of calpain-10 expression did not affect insulin-stimulated glycogen synthesis nor insulin-stimulated phosphorylation of protein kinase B, a key component of the insulin-signalling pathway. |
| 157 | 17647198 | SHP-1 and SHP-2 modulate cellular signals that involve phosphatidylinositol 3-kinase, Akt, Janus kinase 2, signal transducer and activator of transcription proteins, mitogen-activating protein kinases, extracellular signal-related kinases, c-Jun-amino terminal kinases, and nuclear factor-kappaB. |
| 158 | 17604276 | By silencing Akt and blocking Erk1/2 MAPK pathways, we also demonstrate that these signals are downstream to Rac-1/reactive oxygen species production and epidermal growth factor receptor activation. |
| 159 | 17640984 | In addition, Ser(629) of IRS-1 is directly phosphorylated by Akt in vitro. |
| 160 | 17640984 | Cells expressing the Ser(629)Ala mutation, along with increased Ser(636) phosphorylation, had decreased insulin-stimulated association of the p85 regulatory subunit of phosphatidylinositol 3'-kinase with IRS-1 and decreased phosphorylation of Akt at Ser(473). |
| 161 | 17640984 | Finally, in vitro phosphorylation of a Ser(629)-containing IRS-1 fragment with Akt reduces the subsequent ability of ERK to phosphorylate Ser(636/639). |
| 162 | 17719561 | Exposure of cells to ghrelin (10(-7)M) caused rapid activation of Akt. |
| 163 | 17623817 | Conditions accelerating muscle proteolysis are frequently associated with defective phosphatidylinositol 3-kinase (PI3K)/Akt signaling and reduced PI3K-generated phosphatidylinositol 3,4,5-triphosphate (PIP(3)). |
| 164 | 17666488 | We investigated FN mRNA, EDB(+)FN mRNA, and transforming growth factor (TGF)-beta mRNA expression, Akt phosphorylation, Akt kinase activity, and NF-kappaB and AP-1 activation in the retina, heart, and kidney. |
| 165 | 17805301 | During feeding, increases in circulating pancreatic insulin inhibit hepatic glucose output through the activation of the Ser/Thr kinase AKT and subsequent phosphorylation of the forkhead transcription factor FOXO1 (refs 1-3). |
| 166 | 17875968 | Exposure of cultured human umbilical vein endothelial cells to either peroxynitrite (ONOO-) or high glucose significantly inhibited both basal and insulin-stimulated Akt phosphorylation at Ser473 and Akt activity in parallel with increased apoptosis, phosphorylation, and activity of phosphatase and tensin homologue deleted on chromosome 10 (PTEN). |
| 167 | 17875968 | Furthermore, protein kinase B/Akt inhibition induced by ONOO- or high glucose and apoptosis triggered by high glucose could be abolished by transfection of PTEN-specific small interfering RNA, suggesting that PTEN mediated the Akt inhibition by ONOO-. |
| 168 | 17875968 | Interestingly, the ONOO(-)-enhanced PTEN phosphorylation and Akt inhibition can be blocked by LKB1-specific small interfering RNA. |
| 169 | 17875968 | Furthermore, administration of PTEN-specific small interfering RNA suppressed diabetes-enhanced apoptosis and Akt inhibition. |
| 170 | 17875968 | We conclude that hyperglycemia triggers apoptosis by inhibiting Akt signaling via ONOO(-)-mediated LKB1-dependent PTEN activation. |
| 171 | 17575262 | However, the sensitivity to insulin for downstream signaling to control of protein kinase B and glucose uptake was not affected by RBP4. |
| 172 | 17652184 | Adenovirus-mediated overexpression of miR-29a/b/c in 3T3-L1 adipocytes could largely repress insulin-stimulated glucose uptake, presumably through inhibiting Akt activation. |
| 173 | 17652184 | In this paper, we demonstrate that Akt is not the direct target gene of miR-29 and that the negative effects of miR-29 on insulin signaling might be mediated by other unknown intermediates. |
| 174 | 17687071 | Here we report the identification of novel, small-molecule, insulin mimetics that activate the insulin receptor (IR) in vivo and in vitro, stimulate the Akt and extracellular signal-regulated kinase pathways downstream of the IR, and mimic the ability of insulin to stimulate glucose uptake, glycogen synthesis, and lipid synthesis in 3T3-L1 adipocytes. |
| 175 | 17785466 | NR4A3 hyperexpression also led to an increase in insulin-mediated tyrosine phosphorylation of insulin receptor substrate-1 as well as Akt phosphorylation. |
| 176 | 17785466 | Suppression of NR4A3 using lentiviral short hairpin RNA constructs reduced the ability of insulin to stimulate glucose transport and phosphorylate Insulin receptor substrate-1 and Akt. |
| 177 | 17952839 | This reduction was associated with enhanced tyrosine phosphorylation of IRS2 and serine (473) phosphporylation of Akt, indicating improved hepatic insulin signaling. |
| 178 | 17637789 | The subsequent increased arterial inflow to the cavernosal sinoids and shear stress on the endothelium lining penile arteries activates endothelial NO production through Akt phosphorylation of endothelial NO synthase (eNOS). |
| 179 | 17991742 | TrkC expression leads to the constitutive activation of two major effector pathways, namely the Ras-MAP kinase (MAPK) mitogenic pathway and the phosphatidylinositol 3-kinase (PI3K)-AKT pathway mediating cell survival. |
| 180 | 18171435 | Evidence now suggests that the improvements in insulin sensitivity associated with exercise training are also related to changes in the expression and/or activity of proteins involved in insulin signal transduction in skeletal muscle such as the AMP-activated protein kinase (AMPK) and the protein kinase B (Akt) substrate AS160. |
| 181 | 18180317 | GLP-1 treatment also inhibited TNF-alpha-mediated induction of Akt phosphorylation. |
| 182 | 18191647 | The current wisdom indicates that insulin's positive effects, normoglycemia, vasodilation, and anti-inflammation, are mediated by the canonical phosphoinositide 3-kinase (PI3K)/Akt pathway whereas the negative effects are mediated by the mitogen-activated protein kinase (MAPK)/extracellular regulated kinase (ERK) pathway. |
| 183 | 18199585 | Diabetes depressed expression of Kv1.2 and dihydrofolate reductase (DHFR), increased beta-myosin heavy-chain expression, stimulated p38 MAPK, and reduced levels of total Akt and phosphorylated Akt/eNOS, all of which with the exception of myosin heavy chain were attenuated by IGF-I. |
| 184 | 18222959 | Phosphorylation of eNOS Ser1177, AMPK Thr172, and Akt Ser 473 was increased in the adiponectin group (P < 0.05). |
| 185 | 18241357 | Akt/PKB is associated with a downstream insulin signaling, and PKCbeta attenuates insulin-stimulated Akt phosphorylation. |
| 186 | 18241861 | Exposure of beta-cells to GDNF also resulted in phosphorylation of Akt and GSK3beta. |
| 187 | 18321849 | Conversely, ONOO(-) inhibited Akt Ser(473) phosphorylation when wild type LKB1 were reintroduced in HeLa S3 cells. |
| 188 | 18321849 | We conclude that PKCzeta mediates LKB1-dependent Akt inhibition in response to ONOO(-), resulting in endothelial apoptosis. |
| 189 | 18347057 | PDK1 activates a group of kinases, including protein kinase B (PKB)/Akt, p70 ribosomal S6 kinase (S6K), and serum and glucocorticoid-induced protein kinase (SGK), that mediate many of the effects of insulin as well as other agonists. |
| 190 | 18347057 | Activation of PKB is markedly reduced in knock-in mice as a result of lower phosphorylation of PKB at Thr308, the residue phosphorylated by PDK1. |
| 191 | 18347057 | These observations establish the importance of the PDK1-phosphoinositide interaction in enabling PKB to be efficiently activated with an animal model. |
| 192 | 18377870 | We report that expression of a constitutively active form of Akt increases mTOR activity and prevents apoptosis upon AMPK activation. |
| 193 | 18377870 | Expression of a constitutively active form of the mTOR target ribosomal protein S6 kinase (S6K) or of translation factor eIF4E reduced apoptosis by glucose limitation, and co-expression of S6K and eIF4E protected beta cells to the same extent as active Akt. |
| 194 | 18377870 | It is concluded that Akt stimulation of mTOR and subsequent activation of the targets by which mTOR affects protein translation are required and sufficient mechanisms for Akt-mediated survival of beta cells undergoing sustained AMPK activation. |
| 195 | 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. |
| 196 | 18349383 | In the absence of alterations in plasma adiponectin concentrations, acceleration of insulin-stimulated glucose turnover in skeletal muscle of mUCP1 TG mice was accompanied by increased phosphorylated Akt-to-Akt and phosphorylated AMP-activated protein kinase (AMPK)-to-AMPK ratios compared with WT mice. |
| 197 | 18387000 | In the present study, we investigated the importance of the LKB1-AMPK pathway in regulating tumorigenesis in mice resulting from deficiency of the PTEN (phosphatase and tensin homologue deleted on chromosome 10) tumour suppressor, which drives cell growth through overactivation of the Akt and mTOR (mammalian target of rapamycin) kinases. |
| 198 | 18388859 | ProF binds to the transcription factor Foxo1 (Forkhead box O1), a negative regulator of insulin action and adipogenesis, and facilitates the phosphorylation and thus inactivation of Foxo1 by Akt. |
| 199 | 18388859 | Thus, ProF modulates Foxo1 phosphorylation by Akt, promoting adipocyte differentiation. |
| 200 | 18473829 | Erythropoietin controls a variety of signal transduction pathways during oxidative stress that can involve Janus-tyrosine kinase 2, protein kinase B, signal transducer and activator of transcription pathways, Wnt proteins, mammalian forkhead transcription factors, caspases, and nuclear factor kappaB. |
| 201 | 18473907 | Moreover, some experiments have shown that low concentrations of estradiol, induce an increase in the rate of IRS-1 phosphorylation, promotes the association between IRS-1 and the subunit of PI3-k, p85alpha, causes a decrease in the rate of IRS-1 serine phosphorylation and increases the rate of Akt phosphorylation. |
| 202 | 18496818 | We found that the high glucose condition causes significant increasing Ser307 phosphorylation of insulin receptor substrate-1 (IRS-1), leading to reduce insulin-stimulated phosphorylation of Akt. |
| 203 | 18551686 | Compared with a vehicle-treated group, FFA treatment in myotubes was associated with 70.6% reduction in insulin-mediated uptake of glucose, a five-fold increase in serine phosphorylation of IRS-1, 76.9% decrease in tyrosine phosphorylation of IRS-1 and 81.8% decrease in phosphorylation of Akt. |
| 204 | 18551686 | This was accompanied by increase in tyrosine phosphorylation of IRS-1 and phosphorylated Akt and decrease in serine phosphorylation of IRS-1 (p < 0.001). 1,25-Dihydroxyvitamin D also inhibited the FFA-induced reduction in myotube diameter by 35.3% (p < 0.001). |
| 205 | 18599621 | The overfed animals also had decreased insulin sensitivity in the heart, as confirmed by decreased insulin receptor (IR)-beta and IR substrate-1 (Irs1) phosphorylation, increased phosphatase, non-receptor type 1 (Ptpn1)-IR-beta association, decreased -Irs1-associated activity, and reduction in anti-phospho Akt1 phosphorylation. |
| 206 | 18669627 | ADRP ASO increased the phosphorylation of insulin receptor substrate (IRS)1, IRS2, and Akt, and decreased gluconeogenic enzymes and PKCepsilon, consistent with its insulin-sensitizing action. |
| 207 | 18599524 | In the renal cortex of diabetic rats, the increase in Akt phosphorylation is associated with enhanced phosphorylation of tuberin, decreased OGG1 protein expression, and 8-oxodG accumulation. |
| 208 | 18599524 | High glucose also resulted in downregulation of OGG1 protein expression, paralleling its effect on Akt and tuberin. |
| 209 | 18599524 | Hydrogen peroxide stimulates Akt and tuberin phosphorylation and decreases OGG1 protein expression. |
| 210 | 18599524 | Hyperglycemia in type 1 diabetes and treatment of proximal tubular epithelial cells with high glucose leads to phosphorylation/inactivation of tuberin and downregulation of OGG1 via a redox-dependent activation of Akt in renal tubular epithelial cells. |
| 211 | 17949249 | Renal cortical activity and expression of Akt and mTOR (kinase assay, western blotting) were determined in streptozotocin-diabetic rats (D) with different levels of glycemic control (blood glucose 22.0+/-1.0, 13.4+/-1.5, 8.1+/-0.4 mmol/l, p<0.05 between the groups), achieved by varying insulin treatment (0, 4 and 12 IU/day), and in control rats with (C4) or without (C) chronic insulin administration. |
| 212 | 17949249 | Renal Akt activity was reduced in D rats without insulin treatment and severe hyperglycemia (D-0, -62 %, p<0.01 vs. |
| 213 | 17949249 | Moreover, insulin activated renal Akt (+82 %, p<0.01), but not mTOR in C4. |
| 214 | 17949249 | In conclusion, glycemic control and intensity of insulin treatment are important modulators of renal Akt and mTOR activity in diabetes. |
| 215 | 18549351 | The enhanced secretion of CgA and Sg II seemed to be mediated by an activation of protein kinase Akt via PI3K (phosphoinositide 3-kinase). |
| 216 | 18549351 | In accordance with this, inhibition of PI3K activity and, thereby, reduced phosphorylation of Akt was shown to enhance Pdcd4 expression. |
| 217 | 18549351 | Our results are of particular interest, as we observed that pioglitazone, an oral medication used in the treatment of Type 2 diabetes, decreased Pdcd4 levels, activated Akt, increased CgA and Sg II secretion and augmented PC1 protein in Bon-1 cells. |
| 218 | 18691554 | Using a fluorescent assay based upon a novel pseudo-substrate of PDI, flow cytometry and immunological techniques, we have demonstrated the presence of PDI on the surface of pMP (termed msPDI) and its ability to influence insulin-mediated Akt phosphorylation (Thr308) in 3T3-L1 fibroblasts. |
| 219 | 18835934 | Ang-1 gene therapy causes a significant increase in Akt and eNOS expression and HIF-1alpha stabilization. |
| 220 | 18973876 | Insulin phosphorylated its receptor in the neuroblastoma cells but not in astrocytes and, like IGF-1, increased ERK1/2 and Akt phosphorylation. |
| 221 | 19011679 | Insulin stimulated expression of aPKCzeta (p<0.001) and Akt1 (p<0.001) was decreased in muscle of LBW men when compared to insulin stimulated controls. |
| 222 | 19114996 | Low-intensity electrical current (or mild electrical stimulation; MES) influences signal transduction and activates phosphatidylinositol-3 kinase (PI3K)/Akt pathway. |
| 223 | 19114996 | Because insulin resistance is characterized by a marked reduction in insulin-stimulated PI3K-mediated activation of Akt, we asked whether MES could increase Akt phosphorylation and ameliorate insulin resistance. |
| 224 | 18266981 | Our results suggests that the effect of RSV is non-insulin dependent and triggers some of the similar intracellular insulin signalling components in myocardium such as eNOS, Akt through AMPK pathway and also by regulating the caveolin-1 and caveolin-3 status that might play an essential role in Glut-4 translocation and glucose uptake in STZ- induced type-1 diabetic myocardium. |
| 225 | 19330070 | The work of numerous different researchers indicates a role of PKB in regulating insulin-stimulated glucose uptake. |
| 226 | 19330070 | Activation of PKB alpha is then achieved at the plasma membrane by phosphorylation of Thr308 in the activation-loop of the kinase domain and Ser473 in the carboxy-terminal regulatory region, respectively. 3-Phosphoinositide-dependent protein kinase-1 (PDK1) is responsible for T308 phosphorylation. |
| 227 | 18564176 | Akt phosphorylation followed by phosphorylation of eNOS (Ser1177) was observed with glimepiride treatment in HUVEC. |
| 228 | 19171794 | CoPP significantly increased HO-1 activity, phosphorylated AKT and phosphorylated AMP kinase, and serum adiponectin in ZDF rats. |
| 229 | 19188511 | In contrast, blockade of AMP-activated protein kinase, calcium/calmodulin-dependent kinase II, calcium/calmodulin-dependent kinase kinase, serine/threonine protein kinase B, protein kinase A, extracellular signal-regulated kinase 1/2, and p38 mitogen-activated protein kinase did not affect nucleotide-mediated eNOS phosphorylation. |
| 230 | 19218147 | Akt is also a factor in the pathomechanism of diabetes as it determines beta-cell apoptosis of Langerhans islets and insulin sensitivity of the cells. |
| 231 | 19218147 | Several studies revealed that some of the marketed drugs including statins, thiazolidinediones and ACE inhibitors modulate Akt activity. |
| 232 | 18801483 | The anti-apoptotic effect of gliclazide was associated with an increase in PKB activity and a decrease in caspase-3 and -9 activities. |
| 233 | 19188427 | In contrast, IL-6 increased Akt phosphorylation (Ser473) in hindlimb skeletal muscle and enhanced whole-body glucose disappearance and glucose uptake during the clamp. |
| 234 | 19208911 | Phosphorylation of two members of the TBC1 domain family of proteins, Akt substrate of 160 kDa (AS160, also known as TBC1D4) and TBC1D1, has been implicated in the regulation of glucose transport in skeletal muscle. |
| 235 | 19208911 | AMP-activated protein kinase (AMPK) and Akt, both activated by contraction, can each phosphorylate AS160 and TBC1D1 in cell-free assays. |
| 236 | 19251743 | AT1R blockade also originated a dramatic increase in the phosphorylation of Akt and glycogen synthase kinase-3beta. |
| 237 | 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. |
| 238 | 19357831 | Previous findings in rodents used as a model of diabetes suggest that insulin activation of atypical protein kinase C (aPKC) is impaired in muscle, but, unexpectedly, conserved in liver, despite impaired hepatic protein kinase B (PKB/Akt) activation. |
| 239 | 19362713 | In contrast, when only costimulatory signals were provided through CD28, Ly49A engagement did not block p38 MapK or Akt phosphorylation. |
| 240 | 19235132 | In this study, we investigated the role of protein kinase B (Akt) and p42/44 mitogen-activated protein kinase (ERK 1/2) signaling pathways in mediating the mitogenic action of INS in VSMCs. |
| 241 | 19235132 | Incubation of rat VSMCs with INS (100 nM) for 10 min resulted in an increase of Akt phosphorylation by 6-fold (p<0.001) and ERK 1/2 phosphorylation by 3-fold (p<0.001). |
| 242 | 19235132 | Prolonged treatment of VSMCs with INS for 24 h did not have an effect on either Akt or ERK1/2 phosphorylation. |
| 243 | 19235132 | These results indicate that INS acts through Akt and ERK 1/2 signaling pathways to up-regulate proliferation of VSMC's. |
| 244 | 19273608 | Insulin stimulation of betaIRKO and betaIRS2KO cells led to blunted activation of phosphatidylinositol 3-kinase and Akt kinase, while surprisingly, glucose failed to activate either kinase but phosphorylated extracellular signal-regulated kinase. |
| 245 | 19289493 | Insulin resistance in Akt2(-/-) mice was inhibited by haplodeficiency of Pten, suggesting that other Akt isoforms can compensate for Akt2 function. |
| 246 | 19336408 | Insulin-induced changes in mtDNA, mitochondrial mass, intracellular ATP content, and transcripts of mitochondrion-associated genes were prevented by blockade of Akt activation with the phosphatidylinositol 3-kinase inhibitor LY294002. |
| 247 | 19343564 | In Reg3alpha-expressing cells, we detected 2.2- and 2.5-fold increased levels of cyclin D1 and CDK4, respectively, which paralleled a 1.8-fold increase in the rate of Akt phosphorylation. |
| 248 | 19343564 | Our results suggest that Reg3alpha stimulates beta-cell replication, by activating Akt kinase and increasing the levels of cyclin D1/CDK4. |
| 249 | 19416712 | Insulin-stimulated activation of Akt and suppression of gluconeogenesis in hepatocytes are enhanced by APPL1 overexpression, but are attenuated by APPL1 knockdown. |
| 250 | 19416712 | APPL1 interacts with Akt and blocks the association of Akt with its endogenous inhibitor tribble 3 (TRB3) through direct competition, thereby promoting Akt translocation to the plasma membrane and the endosomes for further activation. |
| 251 | 19416712 | These results suggest that the potentiating effects of APPL1 on insulin-stimulated suppression of hepatic glucose production are attributed to its ability in counteracting the inhibition of Akt activation by TRB3. |
| 252 | 19455054 | BHE elevated antiapoptotic proteins Bcl-2 and heme oxygenase-1 and stimulated the phosphorylation of survival protein Akt simultaneously decreasing the apoptotic proteins Bax and Src. |
| 253 | 19541499 | The serine-threonine kinase Akt, also known as protein kinase B, is one of the major downstream targets of the PI3K pathway and is negatively regulated by phosphatase and tensin homologue deleted on chromosome 10. |
| 254 | 19543271 | Akt kinase is activated by transforming growth factor-beta1 (TGF-beta) in diabetic kidneys, and has important roles in fibrosis, hypertrophy and cell survival in glomerular mesangial cells. |
| 255 | 19543271 | However, the mechanisms of Akt activation by TGF-beta are not fully understood. |
| 256 | 19543271 | Here we show that TGF-beta activates Akt in glomerular mesangial cells by inducing the microRNAs (miRNAs) miR-216a and miR-217, both of which target PTEN (phosphatase and tensin homologue), an inhibitor of Akt activation. |
| 257 | 19543271 | Akt activation by these miRs led to glomerular mesangial cell survival and hypertrophy, which were similar to the effects of activation by TGF-beta. |
| 258 | 19543271 | These studies reveal a mechanism of Akt activation through PTEN downregulation by two miRs, which are regulated by upstream miR-192 and TGF-beta. |
| 259 | 18839335 | The molecular mechanism of TIMP-1 inhibition of resistin-mediated cytotoxicity appeared to involve Akt phosphorylation and activation of IkB-alpha phosphorylation. |
| 260 | 18839335 | Resistin treatment suppressed Akt phosphorylation and activated IkB-alpha phosphorylation, which could be attenuated by TIMP-1. |
| 261 | 19463904 | GLP-1 protected against this MG-induced apoptosis, which corresponded to the phosphorylation of PI3K, Akt, and mTOR, as well as the upregulation of GCLc and the restoration of the redox imbalance. |
| 262 | 19463904 | Inhibitors of PI3K (LY294002), Akt (Akt-I), and mTOR (rapamycin) reduced the GLP-1-induced GCLc upregulation and its protection against MG-induced PC12 apoptosis. |
| 263 | 19531641 | This correlated with the ability of rosiglitazone to enhance insulin sensitivity for stimulation of protein kinase B (Akt) phosphorylation and glucose transport; rosiglitazone also corrected high-glucose-induced insulin resistance in L6 cells. |
| 264 | 19545622 | Because the effect of CaM is mediated through CaM-dependent protein kinase II (CaMKII), we have investigated here the potential role of CaMKII in H(2)O(2)-induced ERK1/2 and PKB phosphorylation by using pharmacological inhibitors of CaM and CaMKII, a CaMKII inhibitor peptide, and siRNA knockdown strategies for CaMKII alpha. |
| 265 | 19545622 | These results demonstrate that CaMKII plays a critical upstream role in mediating the effects of H(2)O(2) on ERK1/2, PKB, and IGF-1R phosphorylation. |
| 266 | 19596003 | The phosphorylation of Akt and the activations of Cdc42 and Rac1 were significantly increased by adiponectin. |
| 267 | 19596003 | Adiponectin increased the migration activity of EPCs, which was completely inhibited by a PI3-kinase inhibitor. siRNA of Cdc42 or Rac1 completely inhibited the adiponectin-induced migration, but siRNA of Akt had no effects, indicating that adiponectin promotes the migration activities of EPCs mainly through PI3-kinase/Cdc42/Rac1. |
| 268 | 19699714 | Interestingly, Rg3 dramatically increased IRS-1 protein levels, while the protein level of Akt was not affected. |
| 269 | 19523145 | It induced activation of glucose metabolism-related signalling pathway via protein kinase B (Akt) and protein kinase C zeta/lambda (PKC zeta/lambda)-glucose transporter-4 (GLUT4) proteins. |
| 270 | 19523145 | In the skeletal muscle, expression and translocation of GLUT4 protein, phosphorylation of Akt and PKC zeta/lambda, and phosphofructokinase and hexokinase enzyme activities increased significantly by DHEA injection. |
| 271 | 19556298 | At the protein level, phosphorylation of the insulin receptor, IRS1 and PKB was reduced and there was impaired translocation of GLUT4 to the cell surface. |
| 272 | 19615701 | Castration elevated the blood glucose level, which was accompanied by inhibitory effect on serum insulin, Akt phosphorylation, GLUT4 expression and its plasma membrane population, glucose uptake, glycogen and glycogen synthase activity, and stimulatory effect on GLUT2 expression and glycogen phosphorylase activity in tissues studied. |
| 273 | 19808019 | The increased insulin sensitivity in Gpx1(-/-) mice was attributed to insulin-induced phosphatidylinositol-3-kinase/Akt signaling and glucose uptake in muscle and could be reversed by the antioxidant N-acetylcysteine. |
| 274 | 19282820 | HFCS-55 induced a downregulation of the insulin signaling pathway, as indicated by attenuated (ser473)phosphorylation of AKT1. |
| 275 | 19717727 | The insulin-induced relaxation was inhibited by treatment with an Akt inhibitor in control and diabetic aortas, but not in the HI-diabetic aorta. |
| 276 | 19717727 | These results suggest that the plasma insulin level has a close relation to the level of aortic PDK-1/Akt (at Thr(308))/NOS activities, and that reduced actions of the PDK-1/Akt (at Thr(308)) signal pathway may contribute to the impairments of insulin-induced endothelial functions seen in hyperinsulinemic diabetes. |
| 277 | 19740738 | We show that a mutant of TBC1D1, in which several Akt sites have been converted to alanine, is considerably more inhibitory to insulin-stimulated GLUT4 translocation than wild-type TBC1D1. |
| 278 | 19740738 | We also show that in addition to Akt activation, activation of the AMP-dependent protein kinase partially relieves the inhibition of GLUT4 translocation by TBC1D1. |
| 279 | 19741193 | No differences in insulin or PDGF-induced phosphorylation of ERK-1/2 or components of the Akt pathway (Akt-Ser473, Akt-Thr308, and GSK-3beta) were apparent between the two populations. |
| 280 | 19748889 | Using selective enzyme inhibitors, overexpression of dominant-negative Akt, and Akt siRNA, it was demonstrated that GIP promoted beta-cell survival via Akt-dependent suppression of p38 MAPK and JNK and that combined inhibition was sufficient to explain the entire pro-survival responses to GIP during STS treatment. |
| 281 | 19802467 | However, insulin or SCF could activate the phosphorylation of ERK1/2 and AKT in the diabetic cortex. |
| 282 | 19802467 | The results suggest that SCF may protect the brain from apoptosis in diabetes and that the mechanism of this protection may, at least in part, involve activation of the ERK1/2 and AKT pathways. |
| 283 | 19657071 | Akt phosphorylation in response to insulin was reduced in adipose and skeletal muscle of adult rats following exposure to LP diet in early life when compared to control-fed animals, but this was only apparent in males. |
| 284 | 19720798 | Chemerin induces insulin resistance in human skeletal muscle cells at the level of insulin receptor substrate 1, Akt and glycogen synthase kinase 3 phosphorylation, and glucose uptake. |
| 285 | 19755525 | Administration of erythropoietin (EPO) induced phosphorylation of Akt and GSK-3beta and reduced infarct size (% risk area) from 47.4 +/- 5.2% to 23.9 +/- 3.5% in LETO hearts. |
| 286 | 19755525 | However, neither phosphorylation of Akt and GSK-3beta nor infarct size limitation was induced by EPO in OLETF rats. |
| 287 | 19837872 | PGE(2)-mediated JNK1 activation, through dephosphorylation of Akt and FOXO1, leads to nuclear accumulation of FOXO1 and nucleocytoplasmic shuttling of PDX1, finally resulting in defective GSIS in pancreatic beta-cells. |
| 288 | 19901535 | PPTR-1, as well as its mammalian homolog B56beta, specifically target the PP2A enzyme to AKT and mediate the dephosphorylation of this important kinase at a conserved threonine residue. |
| 289 | 19929783 | HCV directly causes insulin resistance through HCV core protein-elicited proteasomal degradation of insulin receptor substrates and subsequent inactivation of intracellular insulin signaling molecules such as Akt. |
| 290 | 20011604 | This occurs through protein kinase C (PKC)alpha activation since dowregulation of PKCalpha expression using specific siRNA or blockade of its activity using chemical inhibition affects the FGF-2-dependent Ser473 Akt phosphorylation. |
| 291 | 20011604 | Furthermore these data unveil a novel role for PLCgamma1 as a mediator of PI3K-dependent Akt activation and as a novel key regulator of different Akt-dependent processes. |
| 292 | 20029537 | We have demonstrated that insulin-like growth factor type 1 receptor (IGF-1R) plays a role in transducing the effect of H2O2, leading to protein kinase B (PKB) phosphorylation. |
| 293 | 19531027 | In support of this, Western blotting revealed that incubation of cells with IL-4 resulted in increased phosphorylation of Akt (also called protein kinase B), a downstream target of PI3K. |
| 294 | 19726550 | The current study hypothesized that alteration of the Akt signaling pathway by hyperglycemia may contribute to p38 MAPK activation and development of diabetic nephropathy. |
| 295 | 19726550 | In addition, blockade of the phosphatidylinositol-3 kinase/Akt pathway with LY294002 and silencing of Akt expression with Akt small interfering RNA induced p38 MAPK phosphorylation in the absence of HG. |
| 296 | 19726550 | These results collectively suggest that downregulation of Akt activation during long-term hyperglycemia contributes to enhanced p38 MAPK activation and RPTC apoptosis. |
| 297 | 19726550 | Mechanism of downregulation of Akt activation in 6-mo streptozotocin diabetic kidneys was attributed to decreased Akt-heat shock protein (Hsp) 25, Akt-p38 interaction, and decreased PTEN activity. |
| 298 | 19726550 | Thus PTEN or Hsp25 could serve as potential therapeutic targets to modulate Akt activation and control p38 MAPK-mediated diabetic complications. |
| 299 | 19897488 | However, Akt operates well below its capacity to facilitate maximal GLUT4 translocation. |
| 300 | 19902175 | In vitro, TNF-alpha enhanced mRNA levels of gene sets related to apoptosis and Akt and p53 but not mitochondrial or cell-cycle pathways. |
| 301 | 19923418 | Recombinant AMPK, but not Akt1, Akt2, or PKCzeta, phosphorylated purified muscle TBC1D4 on S711 in vitro. |
| 302 | 19933838 | Protein kinase B (PKB)/Akt is considered to be a key target downstream of insulin receptor substrate 2 (IRS2) in the regulation of beta-cell mass. |
| 303 | 19933838 | Additionally, our signaling analyses revealed that PKBalpha, but not PKBbeta or PKBgamma, is specifically activated by overexpression of IRS2 in beta-cells and is required for IRS2 action in the islets. |
| 304 | 19933999 | We show that pharmacological activation or inhibition of CB1 receptor activity exerts a differential effect with regard to MAP kinase- and PKB-directed signaling. |
| 305 | 19944677 | Both young and adult SHRs showed significant downregulated expression of PI3-kinase and decreased insulin-stimulated phosphorylations of Akt and eNOS in vascular tissues. |
| 306 | 20068149 | Although lean female MKR mice are insulin resistant and glucose intolerant, displaying accelerated mammary gland development and enhanced phosphorylation of IR/IGF-IR and Akt in mammary tissue, in the context of three different mouse models of breast cancer, these metabolic abnormalities were found to accelerate the development of hyperplastic precancerous lesions. |
| 307 | 19766294 | VSMC exposed to DL-homocysteine or NMDA (100 micromol/L for both; 5 min-8 hours), were investigated by measuring: i) phosphorylation of ERK1/2, p38MAPK (signaling molecules of MAPK pathway) and Akt and p70S6K (signaling molecules of PI3-K pathway) by western blot; ii) synthesis and secretion of MMP-2 (western blot); iii) activation of MMP-2 (gelatin zimography). |
| 308 | 19781600 | The treatment of oxidized low density lipoprotein (oxLDL) decreased ATP contents, mitochondrial respiration activity, mRNA expressions of OXPHOS subunits and IRS-1/2 and insulin-mediated phosphorylations of Akt and AMP-activated protein kinase (AMPK). |
| 309 | 19965940 | Decreased IRS2 attenuated the phosphorylation of Akt and, subsequently, PDX-1 protein levels were lowered in olanzapine-treated rats. |
| 310 | 20398956 | Akt and eNOS activity was analyzed by western blot. |
| 311 | 20534540 | We demonstrate that this effect is mediated by activation of the serine/threonine kinase, protein kinase B, which inhibits AMPK by phosphorylating serine 485. |
| 312 | 20573722 | Glucagon secretion, insulin and IGF-IR autophosphorylation, and insulin receptor substrate (IRS)-1, IRS-2, phosphatidylinositol kinase (PI3K) (p85 alpha), and serine-threonine protein kinase (Akt) phosphorylated (active) forms were measured. |
| 313 | 20701589 | We studied TBC1D1 phosphorylation on three predicted AMPK (AMP-activated protein kinase) phosphorylation sites (Ser231, Ser660 and Ser700) and one predicted Akt phosphorylation site (Thr590) in control mice, AMPK?2 inactive transgenic mice (AMPK?2i TG) and Akt2-knockout mice (Akt2 KO). |
| 314 | 20839494 | Total Akt was negatively correlated with IL-1beta (r = -0.45, p = 0.046), IL-6 (r = -0.44, p = 0.052) and TNF-alpha (r = -0.51, p = 0.025). |
| 315 | 20724582 | Chemerin reduced insulin-stimulated Akt1 phosphorylation and activation of 5'AMP-activated protein kinase (AMPK) in the skeletal muscle, but had no effect on Akt phosphorylation and insulin-stimulated AMPK activation in the liver and gonadal adipose tissue. |
| 316 | 20733001 | After a meal, insulin suppresses lipolysis through the activation of its downstream kinase, Akt, resulting in the inhibition of protein kinase A (PKA), the main positive effector of lipolysis. |
| 317 | 20733001 | Here, we describe a noncanonical Akt-independent, phosphoinositide-3 kinase (PI3K)-dependent pathway that regulates adipocyte lipolysis using restricted subcellular signaling. |
| 318 | 20733001 | In contrast, the phosphorylation of another PKA substrate, hormone-sensitive lipase (HSL), remains Akt dependent. |
| 319 | 18174452 | Akt was recognized by an O-GlcNAc specific lectin, and glucosamine increased the amounts of Akt protein in these lectin precipitates. |
| 320 | 18174452 | These results suggest that elevated protein O-GlcNAc modification through the HBP impairs angiogenesis in endothelial cells, possibly by inhibiting Akt signaling. |
| 321 | 18511290 | The two isoforms of this recently discovered family, PHLPP1 and PHLPP2, control the amplitude and duration of signaling of Akt and PKC by catalyzing the dephosphorylation of the hydrophobic phosphorylation motif, a C-terminal phosphorylation switch that controls these kinases. |
| 322 | 18511290 | By specifically dephosphorylating the hydrophobic motif, PHLPP controls the degree of agonist-evoked signaling by Akt and the cellular levels of PKC. |
| 323 | 18511290 | This review focuses on the function of PHLPP1 and PHLPP2 in modulating signaling by Akt and PKC. |
| 324 | 18555856 | We measured basal and insulin-stimulated glucose uptake, glycogen accumulation, phosphoinositide 3 (PI-3) kinase activity, and Akt phosphorylation in primary skeletal muscle culture from subjects with type 2 diabetes mellitus incubated with or without various concentrations of PMI 5011. |
| 325 | 18555856 | PMI 5011 treatment did not appear to significantly affect protein abundance for IRS-1, IRS-2, PI-3 kinase, Akt, insulin receptor, or Glut-4. |
| 326 | 19234337 | However, TNF-alpha-induced Akt phosphorylation was blocked, and inhibiting Akt dramatically decreased CCL2 production. |
| 327 | 20182580 | We also discuss issues related to the intricate mTORC2-AktmTORC1 loop and the contradictory regulation of Akt phosphorylation and stabilization of Akt by mTORC2. |
| 328 | 20375985 | Furthermore, visfatin induced tyrosine phosphorylation of the insulin receptor, activated downstream insulin signaling pathways such as Erk-1, Akt, and p38 MAPK, and markedly increased the levels of TGFbeta1, PAI-1, type I collagen, and MCP-1 in both renal cells. |
| 329 | 20584641 | Western blotting was applied to detect the phosphorylation and protein expression of PI3K and PKB and the protein expression of GLUT4. |
| 330 | 20382513 | Furthermore, the augmented expression of CTGF and TIMP-2 in HG-exposed cells was mediated by Akt activation and TGF-beta/Smad signaling through PKCbeta2-responsive signaling pathways. |
| 331 | 20649634 | Collectively, these results suggest that GLP-1 receptor agonist protects beta cells from hIAPP-induced cell death partially through the activation of AKT pathway and improved mitochondrial function. |
| 332 | 19754670 | Paradoxically, inhibition of GSK-3beta phosphorylation also augmented monocyte migration in THP-1, ND and diabetic monocytes through phosphorylation of AKT and activation of Rho-A that was independent of GSK. |
| 333 | 20600772 | In the liver from diabetic treated group, the insulin-stimulated AKT phosphorylation was higher and the PEPCK protein levels were reduced. |
| 334 | 19879746 | The mechanism may be, at least partly, attributed to enhancement of PI3K/HSP90/eNOS/Akt cascade, reduction in plasma resistin level, down-regulation of PTEN and slight modification of oxidative state. |
| 335 | 20601126 | We found that Ang II significantly inhibited insulin-induced phosphorylation of tyrosine 608 of IRS-1 and serine 473 of Akt, a downstream member of anti-mitogenic pathway of insulin. |
| 336 | 20810672 | In lung tissue, metformin did not activate AMPK but inhibited phosphorylation of insulin-like growth factor-I receptor/insulin receptor (IGF-1R/IR), Akt, extracellular signal-regulated kinase (ERK), and mTOR. |
| 337 | 20306473 | While CDN and CP had no effect, activation of NFkappaB, Akt and glucose transporter-2 levels were decreased, insulin receptor substrate 1 (IRS-1) activation increased in livers of CDNC-rats. |
| 338 | 20823563 | Moreover, 7-O-MA stimulated the reactivation of insulin-mediated phosphorylation of phosphatidylinositol 3-kinase (PI3K)-linked protein kinase B (Akt/PKB) and adenosine 5'-monophosphate-activated protein kinase (AMPK) in high glucose-induced, insulin-resistant HepG2 cells, and this effect was blocked by either LY294002, a PI3K inhibitor, or compound C, an AMPK inhibitor. |
| 339 | 20847591 | Forced expression of a constitutively active form of Akt containing a myristoylation signal sequence (MyrAkt) in these cells with the use of an adenoviral vector resulted in the phosphorylation of p70 S6 kinase, a downstream target of mTOR signaling, and this effect was inhibited by rapamycin. |
| 340 | 20829391 | To investigate the impact of increased expression of SHIP2 in the brain, we further employed transgenic mice overexpressing SHIP2 and found that increased amounts of SHIP2 induced the disruption of insulin/IGF-I signaling through Akt. |
| 341 | 20872961 | The phosphoinositide 3-kinase (PI3K)/phosphatase and tensin homolog (PTEN)/Akt axis is a key signal transduction node that regulates crucial cellular functions, including insulin and other growth factors signaling, lipid and glucose metabolism, as well as cell survival and apoptosis. |
| 342 | 20549472 | Studies over the last two decades have firmly established the importance of AKT in the regulation of cell survival, proliferation, and insulin-dependent metabolic cell responses. |
| 343 | 20693566 | In previous studies on the lipogenic effects of GIP, it was shown to increase adipocyte lipoprotein lipase (LPL) activity in both differentiated 3T3-L1 cells and human adipocytes through a pathway involving activation of protein kinase B (PKB)/Akt. |
| 344 | 20693566 | Subsequent studies established that GIP increased phosphorylation of Serine 133 in cAMP-response element binding protein (CREB) and the nuclear localization of cAMP-responsive CREB coactivator 2 (TORC2) through a pathway involving phosphatidylinositol 3-kinase (PI3-K), PKB, and AMP-activated protein kinase (AMPK). |
| 345 | 20730455 | Also, intracellular signaling is different with respect to insulin, with a prevalent activation of the ERK rather than the AKT pathway. |
| 346 | 20683642 | The results showed that 100 nM insulin could induce SOCS3 mRNA expression but not protein expression, and overexpression of SOCS3 decreased IRS1 protein level, insulin-stimulated IRS1 tyrosine phosphorylation, PI3K activation, and Akt phosphorylation, but increased IRS1 serine phosphorylation in porcine primary adipocytes. |
| 347 | 20728450 | In cultured cardiomyocyte experiments, Rab4a was induced by pharmacological inhibition of Akt as well as by specific knockdown of Akt2 with siRNA. |
| 348 | 20813836 | Additionally, we show for the first time that although palmitate increases IRS-1 serine 307 phosphorylation in 3T3L1 adipocytes, AKT serine 473 phosphorylation is enhanced, not reduced, by palmitate. |
| 349 | 20586815 | Exposure of primary VSMCs to high glucose (25 mM) led to the up-regulated expression of SDF-1? and CXCR4, activated PI-3K/Akt signalling, and consequently promoted the proliferation and chemotaxis of VSMCs. |
| 350 | 20816670 | On molecular assay, 8-OHdG antagonized the action of GTP on Rac, a small GTP binding protein, without affecting Rac-guanosine exchange factor (GEF) or phosphoinositide 3-kinases (PI3K) activity. |
| 351 | 20926386 | Knockdown of Ogt decreased Dilp2, Dilp3, and Dilp5 production, with reduced body size and decreased phosphorylation of Akt in vivo. |
| 352 | 20926386 | In contrast, knockdown of Oga increased Dilp2, Dilp3, and Dilp5 production, increased body size, and enhanced phosphorylation of Akt in vivo. |
| 353 | 20926386 | Furthermore, phosphorylation of Akt stimulated by extraneous insulin in an ex vivo cultured fat body of third instar larvae was diminished in strains subjected to IPC knockdown of Ogt or Oga. |
| 354 | 21109194 | These defects were normalized by expression of a constitutively active form of Akt in the islets of ?DKO mice, preserving insulin secretion in response to glucose. |
| 355 | 20876720 | Consistent with increased insulin sensitivity, mice with ablated hepatic leptin signaling had increased insulin-stimulated phosphorylation of Akt in the liver. |
| 356 | 20938636 | Before training, reductions in insulin-stimulated R (d), together with impaired insulin-stimulated glycogen synthase fractional velocity, Akt Thr³?? phosphorylation and phosphorylation of TBC1D4 at Ser³¹?, Ser??? and Ser??¹ were observed in skeletal muscle from diabetic patients. |
| 357 | 20938636 | This happened independently of increased TBC1D4 protein content, but exercise-training did not normalise Akt phosphorylation in diabetic patients. |
| 358 | 20938636 | In both groups, training-induced improvements in insulin-stimulated R(d) (~20%) were associated with increased muscle protein content of Akt, TBC1D4, ?2-AMP-activated kinase (AMPK), glycogen synthase, hexokinase II and GLUT4 (20-75%). |
| 359 | 21136963 | Mediators of insulin resistance operate through activation of various protein kinase C isoforms, I?B kinase ? (IKK?), and/or c-Jun N-terminal kinase, and subsequent inhibition of the proximal insulin signaling pathway via the insulin receptor substrate 1 and Akt. |
| 360 | 20299332 | This effect was dependent on Akt phosphorylation and associated with decreased O-linked N-acetylglucosamine protein modification of eNOS. |
| 361 | 21073655 | Furthermore, high glucose concentrations led to apoptosis of ?-cells by activation of p38MAPK and p53, and dysfunction of ?-cells through phosphatase and tensih homolog (PTEN)-dependent Jun N-terminal kinase (JNK) activation and protein kinase B (AKT/PKB) inhibition, which induced the translocation of forkhead box O1 and pancreatic duodenal homeobox-1, followed by reduced insulin expression and secretion. |
| 362 | 21073655 | In conclusion, NOX2-derived ROS could play a critical role in high glucose-induced ?-cell dysfunction through PTEN-dependent JNK activation and AKT inhibition. |
| 363 | 21152033 | SRA in adipocytes increases both glucose uptake and phosphorylation of Akt and FOXO1 in response to insulin. |
| 364 | 20950345 | We discovered that Akt phosphorylates Sec24, an essential coat protein II (COPII) component involved in mediating cargo selection for ER-to-Golgi trafficking. |
| 365 | 20930063 | AKT content was reduced and activated AKT was undetectable in IUGR placentas. c-Jun N-terminal kinase content was reduced in IUGR. |
| 366 | 21157483 | Mammalian TOR complex 1 (mTORC1) and mTORC2 exert their actions by regulating other important kinases, such as S6 kinase (S6K) and Akt. |
| 367 | 20962202 | Akt phosphorylation following insulin stimulation in soleus muscle was significantly (25%) higher in Hypoxia than Control (P < 0.05). |
| 368 | 20959631 | Inhibition of Akt signalling leads to insulin resistance and type 2 diabetes, whereas hyperactivation of Akt promotes tumorigenesis. |
| 369 | 20959631 | In this study, we investigate how modest changes in the activity of the Akt signalling pathway, to an extent that might be achieved by drug treatment, would impact on insulin resistance and tumorigenesis. |
| 370 | 20959631 | Using insulin-resistant PDK1(K465E/K465E) PH domain knock-in mice, we found that introducing the PTEN(+/-) mutation to slightly stimulate Akt restored normal insulin sensitivity. |
| 371 | 21047779 | We show that inhibition of Gsk-3 by phosphatidylinositol 3-kinase (PI3K)-mediated activation of Akt also results in reduced DNA methylation at these imprinted loci. |
| 372 | 20966391 | Moreover, inhibition of Akt signaling attenuated the phosphorylation of forkhead box O transcription factor (FOXO)-3a and enhanced atrogin-1 expression, which in turn suppressed BK-?(1) protein levels in human CASMCs. downregulation of vascular BK-?(1) expression in diabetes and in high-glucose culture conditions was associated with FOXO-3a/FBXO-dependent increase in BK-?(1) degradation. |
| 373 | 21144973 | Diabetic cardiomyopathy was characterized by declined diastolic and systolic myocardial performance associated with increased oxidative-nitrative stress, nuclear factor-?B and mitogen-activated protein kinase (c-Jun N-terminal kinase, p-38, p38?) activation, enhanced expression of adhesion molecules (intercellular adhesion molecule-1, vascular cell adhesion molecule-1), tumor necrosis factor-?, markers of fibrosis (transforming growth factor-?, connective tissue growth factor, fibronectin, collagen-1, matrix metalloproteinase-2 and -9), enhanced cell death (caspase 3/7 and poly[adenosine diphosphate-ribose] polymerase activity, chromatin fragmentation, and terminal deoxynucleotidyl transferase dUTP nick end labeling), and diminished Akt phosphorylation. |
| 374 | 21145457 | IP7 affects this pathway by potently inhibiting the PDK1 phosphorylation of Akt, preventing its activation and thereby affecting insulin signaling. |
| 375 | 20870968 | Leptin and amylin alone and in combination activate signal transducer and activator of transcription 3 (STAT3), AMP-activated protein kinase, Akt, and extracellular signal-regulated kinase signaling pathways in hAT ex vivo and hPAs and hPBMCs in vitro; all phosphorylation events were saturable at leptin and amylin concentrations of ?50 and ?20 ng/ml, respectively. |
| 376 | 20618069 | Phenotypes resulted from altering GPX1 and/or SOD1 were partly mediated through these factors, along with protein kinase B and c-jun terminal kinase. |
| 377 | 21209957 | Our results show that palmitate and oleate (0.5 mmol/L, 48 h) induced JNK activation and AKT inhibition which resulted in decreased phosphorylation of FOXO1 following nuclear localization and the nucleocytoplasmic translocation of PDX-1, leading to the reducing of insulin and ultimately dysfunction of pancreatic NIT-1 cells. |
| 378 | 20981553 | In hearts from healthy controls, EPO decreased infarct size (14.36 ± 0.60 and 36.22 ± 4.20% of left ventricle in EPO-treated and untreated hearts, respectively, p < 0.05) and increased phosphorylated forms of Akt, ERK1/2, and their downstream target GSK-3?. |
| 379 | 20981553 | In hearts from STZ-induced diabetic rats, EPO did not decrease infarct size (32.05 ± 2.38 and 31.88 ± 1.87% in EPO-treated and untreated diabetic rat hearts, respectively, NS) nor did it increase phosphorylation of Akt, ERK1/2, and GSK-3?. |
| 380 | 20981553 | In contrast, in hearts from HFD-induced insulin resistance rats, EPO decreased infarct size (18.66 ± 1.99 and 34.62 ± 3.41% in EPO-treated and untreated HFD rat hearts, respectively, p < 0.05) and increased phosphorylation of Akt, ERK1/2, and GSK-3?. |
| 381 | 21270262 | These changes in lipid homeostasis were accompanied by in vivo insulin resistance and impaired glucose tolerance and associated with increased phosphorylation of protein kinase C , inhibition of insulin receptor substrate 1, and a decreased activation of protein kinase B (PKB; also known as Akt) in liver and skeletal muscle in response to insulin. |
| 382 | 18984671 | TRIB3 inhibits insulin-stimulated Akt phosphorylation and subsequent insulin action. |
| 383 | 21186102 | It has been recently shown that nephrin once phosphorilated associates with PI3K and stimulates the Akt dependent signaling. |
| 384 | 21232147 | Left ventricular function, myocardial apoptosis, myocardial ultrastructure, Akt, GSK-3? and NF-?B phosphorylation, the expression of TNF-?, IL-6 and myeloperoxidase (MPO) were examined. |
| 385 | 21232147 | TSN also enhanced Akt and GSK-3? phosphorylation and inhibited NF-?B phosphorylation, resulting in decreased TNF-?, IL-6 and MPO activities. |
| 386 | 21094196 | In addition, the phosphorylation of AKT occurred in 10min and was the highest in 30min after the stimulation with ghrelin, which can be blocked by phosphoinositide 3-kinase (PI3K) inhibitor, LY2940002. |
| 387 | 21189286 | To elucidate the mechanism of how insulin signaling induces RDS, bronchoalveolar epithelium-specific Akt1 transgenic (TG) mice were generated. |
| 388 | 21178610 | Elovl5 activity regulates hepatic C20-22 PUFA content, signaling pathways (Akt and PP2A) and transcription factors (SREBP-1, PPAR?, FoxO1 and PGC1?) that control fatty acid synthesis and gluconeogenesis. |
| 389 | 20154404 | OLM + AZL may improve the severely impaired EDHF-mediated responses in diabetic ApoE(-/-) mice, in which activation of the endothelial Akt - eNOS pathway may be involved. |
| 390 | 20676904 | Activation of hypertrophic and cell signaling pathways was determined by assessing protein expression levels of atrial natriuretic peptide (ANP), ?-sarcomeric actin, p53, Bax and Bcl-2 and phosphorylation of p38, ERK and Akt. |
| 391 | 20676904 | ANG II and PE significantly increased levels of ANP and ?-actin and phosphorylation of p38 and ERK in the non-diabetic but not in the diabetic group; phosphorylation of Akt was unchanged irrespective of group or treatment. |
| 392 | 21177856 | Akt, downstream from phosphatidylinositol 3-kinase in insulin signaling, phosphorylates FoxO1 at Thr(24), Ser(256), and Ser(319), negatively regulating its function. |
| 393 | 17873277 | Together, our results identify a novel role for iPLA(2)-catalyzed AA release and its metabolism by 12/15-LOX in coupling SR-A-mediated macrophage adhesion to Rac and Cdc42 activation. |
| 394 | 18174526 | Fatty acids induced nuclear localization of Foxo1 at 4 h when Akt activity was increased, indicating that FoxO1 activation was not mediated by JNK inhibition of Akt. |
| 395 | 21239445 | IGF-I induces skeletal muscle hypertrophy by stimulating protein synthesis and suppressing the protein degradation pathway; the downstream signaling pathways Akt-mammalian target of rapamycin (mTOR)-p70-kDA-S6-kinase (p70S6K), and Forkhead box O1 (FoxO1) play essential roles in this regulation. |
| 396 | 20022950 | To explore the mechanism of insulin resistance, we have developed a novel system to activate Akt independently of its upstream effectors as well as other insulin-responsive pathways such as mitogen-activated protein kinase. 3T3-L1 adipocytes were rendered insulin-resistant either with chronic insulin or dexamethasone treatment, but conditional activation of Akt2 stimulated hemagglutinin-tagged glucose transporter 4 translocation to the same extent in these insulin-resistant and control cells. |
| 397 | 21234858 | We conclude that pyridoxine is effective in ameliorating the dysfunction of platelet NO signaling in response to AGEs, through improving PI3K activity, and hence downstream Akt phosphorylation and in turn serine-1177 phosphorylation of NOS-3. |
| 398 | 21241768 | To investigate the functional impact of SIRT1 on the insulin pathway, the activation of insulin downstream effector PKB was evaluated after SIRT1 inactivation by RNAi, SIRT1 overexpression, or resveratrol treatments. |
| 399 | 21241768 | In muscle cells and HEK293 cells, downregulation of SIRT1 reduced, while overexpression increased, insulin-induced PKB activatory phosphorylation. |
| 400 | 20731625 | No effect was observed on Akt and ERK1/2 phosphorylation. (1) Physiological FFA elevations require at least 120 min to induce insulin resistance, (2) that insulin resistance peaks 360 min after initiation of FFA exposure and (3) ceases 210 min after termination of the FFA infusion. |
| 401 | 20888730 | DC260126 could significantly decrease serum insulin levels, improve insulin tolerance and increase Akt phosphorylation levels in liver, suggesting improved insulin sensitivity in DC260126-treated rats. |
| 402 | 19959757 | Ceramide is now recognized as a negative regulator of insulin signaling by impairing protein kinase B (PKB)/Akt activation. |
| 403 | 19996382 | Tribbles homolog 3 (TRIB3) was found to inhibit insulin-stimulated Akt phosphorylation and modulate gluconeogenesis in rodent liver. |
| 404 | 19996382 | We found that 1) skeletal muscle TRIB3 protein levels are significantly elevated in T2DM patients; 2) muscle TRIB3 protein content is inversely correlated with glucose disposal rates and positively correlated with fasting glucose; 3) skeletal muscle TRIB3 protein levels are increased in STZ-diabetic rats, db/db mice, and Zucker fatty rats; 4) stable TRIB3 hyperexpression in muscle cells blocks insulin-stimulated glucose transport and glucose transporter 4 (GLUT4) translocation and impairs phosphorylation of Akt, ERK, and insulin receptor substrate-1 in insulin signal transduction; and 5) TRIB3 mRNA and protein levels are increased by high glucose concentrations, as well as by glucose deprivation in muscle cells. |
| 405 | 17971451 | Insulin action measured by phosphorylation of Akt is not enhanced in muscle, but phosphorylation of AMP-dependent kinase is increased. |
| 406 | 21090814 | Medicinal chemistry studies resulted in an improved Jnk-1 ligand able to increase adiponectin secretion in human adipocytes and increase insulin-induced protein kinase PKB phosphorylation in human hepatocytes, in similar fashion to Jnk-1 siRNA and to rosiglitazone treatment. |
| 407 | 21321316 | The increased hepatic glucose output in KTD was associated with increased hepatic phosphoenolpyruvate carboxykinase expression through attenuated tyrosine phosphorylation of IRS2 and phosphorylation of Akt(Ser473). |
| 408 | 20580385 | Treatment of HGMEC with fenofibrate resulted in transient activation of adenosine monophosphate-activated protein kinase (AMPK), thereby inducing the phosphorylation of Akt and endothelial nitric oxide synthase, leading to nitric oxide production. |
| 409 | 19936080 | In contrast, both compounds bound similarly to a mitochondrial binding site and acutely activated PI-3 kinase-directed phosphorylation of AKT, an action that was not affected by elimination of PPAR gamma activation. |
| 410 | 20380652 | The effects of TSN on Akt and NF-kappaB phosphorylation and the expression of tumour necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) in cardiac tissues were examined. |
| 411 | 20380652 | Western blot analysis showed that TSN treatment enhanced Akt phosphorylation and inhibited NF-kappaB phosphorylation in cardiac tissues. |
| 412 | 21123956 | Effects of ATR on the insulin resistance of age-matched (13-week-old) and unoperated KK/Ay mice were assessed by the glucose tolerance test, circulating adiponectin concentration, and changes in insulin signaling (IRS-1/Akt phosphorylation). |
| 413 | 21123956 | The p53 expression level in the ischemic limb of ATR-treated KK/Ay was significantly decreased and MDM2 phosphorylation level was markedly increased in tandem with the activation of Akt. |
| 414 | 21209093 | Both PKA and AKT inhibitors attenuated AMPK Ser(485/491) phosphorylation resulting from ?-adrenergic blockade and prevented decreases in AMPK activity. |
| 415 | 21228767 | In glomerular endothelial cells, high glucose inhibited the phosphorylation of Akt, endothelial nitric oxide synthase, and glycogen synthase kinase 3?; decreased IRS1 protein expression and increased its association with ubiquitin. |
| 416 | 21441927 | Induced transgenic overexpression of miR-143, but not miR-145, impairs insulin-stimulated AKT activation and glucose homeostasis. |
| 417 | 21441927 | Reduced ORP8 expression in cultured liver cells impairs the ability of insulin to induce AKT activation, revealing an ORP8-dependent mechanism of AKT regulation. |
| 418 | 17327498 | CTGF-driven profibrotic cell signaling as determined by p42/44 MAPK and Akt phosphorylation was unaffected by high glucose. |
| 419 | 18768589 | In accordance with these results, the activation of protein kinase B was detected after visfatin treatment. |
| 420 | 20051463 | EDC3, a component of the mRNA decay and translation repression pathway associated with mRNA processing bodies, was shown to be phosphorylated by AKT downstream of insulin signaling. |
| 421 | 21362377 | TIMP-1 stimulated Akt phosphorylation. |
| 422 | 21393865 | Overexpression of MKL1 or reduction in G-actin decreased insulin-stimulated Akt phosphorylation, whereas reduction of STARS expression increased insulin signaling and glucose uptake. |
| 423 | 21479175 | Treatment of the isolated fat body with human insulin in an in vitro culture system increased total sugar in the fat body and stimulated Akt phosphorylation. |
| 424 | 19249087 | With striking conservation, mammalian B56beta regulates Akt phosphorylation at Thr 308 in 3T3-L1 adipocytes. |
| 425 | 19249087 | This study reveals a conserved role for the B56 regulatory subunit in regulating insulin signaling through AKT dephosphorylation, thereby having widespread implications in cancer and diabetes research. |
| 426 | 21190014 | Insulin action is purportedly modulated by Drosophila tribbles homologue 3 (TRIB3), which in vitro prevents thymoma viral proto-oncogene (AKT) and peroxisome proliferator-activated receptor-? (PPAR-?) activation. |
| 427 | 21194385 | Cortical neurons pretreated with insulin, but not glucose or PA, exhibited blunted phosphorylation of Akt, p70S6K, and GSK-3? with no change detected in ERK. |
| 428 | 21194385 | Inhibition of the phosphatidylinositol 3-kinase (PI3-K) pathway during insulin pretreatment restored acute insulin-mediated Akt phosphorylation. |
| 429 | 21212933 | Reduction in caspase-3 cleavage was linked to the decrease in dependence receptors, neogenin and unc-5 homologue A, as well as the activation of Akt and extracellular signal-regulated protein kinase (ERK) signalling. |
| 430 | 21443457 | EPO also employs the activation of protein kinase B (Akt1) to foster phosphorylation of GSK-3? that appears required for EPO vascular protection. |
| 431 | 21205932 | We showed previously that insulin receptor signaling is diminished in retinas of animal models of diabetes and that downstream Akt signaling is involved in insulin-mediated retinal neuronal survival. |
| 432 | 21205932 | To investigate the mechanism by which PKC impairs insulin-stimulated Akt activity, we assessed various upstream mediators of Akt signaling. |
| 433 | 21205932 | Thus, we next investigated a biophysical mechanism by which insulin signaling could be disrupted and found that disruption of lipid microdomains via cholesterol depletion blocks insulin-induced Akt activation and reduces insulin receptor tyrosine phosphorylation. |
| 434 | 15671479 | Foxo1, a member of the Fox0 subfamily of winged-helix forkhead transcription factors, is a target of insulin and insulin-like growth factor-1 (IGF-1) signal transduction pathways that activate protein kinase B (PKB) in pancreatic beta cells. |
| 435 | 15671479 | Because activation of PKB can require insulin receptor substrate proteins (IRS-1 and IRS-2) and phosphatidylinositol 3-kinase (PI3K), it is of interest to determine whether the activity of Foxo1 is also regulated by heterotrimeric G protein-coupled receptors (GPCRs) with IRS-1 or -2, PI3K, or PKB signaling potential. |
| 436 | 15671479 | Indeed, studies of beta cells have demonstrated that activation of a GPCR for the blood glucose-lowering hormone GLP-1 leads to major alterations of IRS-2, PI3K, and PKB activity. |
| 437 | 15671479 | By promoting nuclear exclusion of Foxo1 in a PKB-mediated manner, GLP-1 may up-regulate the expression of a homeodomain transcription factor (PDX-1) that serves as a master regulator of beta-cell growth and differentiation. |
| 438 | 17908558 | It is widely accepted that phosphatidylinositol 3-kinase (PI3K) signaling to Akt1 is required for physiological cardiac growth. |
| 439 | 17908558 | We also show that activation of the downstream kinase Akt is not required for the mitochondrial adaptations that are secondary to PI3K activation. |
| 440 | 17908558 | Although PI3K signaling to Akt1 is required for cellular growth, Akt-independent pathways mediate the accompanying mitochondrial adaptations. |
| 441 | 21281610 | We observed that rat hippocampus tau was hyperphosphorylated at Ser(396)/Ser(404) (PHF-1 sites) in STZ-induced DM model, accompanied by lowered phosphorylation levels of Akt, GSK-3 and PP-2A. |
| 442 | 21333731 | Furthermore, the activation of Akt and MAPKs was involved in the effect of RSG on Nrf2, HO-1 and COX-2. |
| 443 | 18487449 | Downregulation of PAT proteins also produced insulin resistance, as indicated by decreased insulin stimulation of Akt phosphorylation (P < 0.001). |
| 444 | 20103738 | Hepatic phosphoenolpyruvate carboxykinase (PEPCK) mRNA expression and red skeletal muscle PKB Ser(473) phosphorylation were used to assess tissue-specific insulin sensitivity. mRNA expression of the hypothalamic mineralocorticoid receptor was fivefold upregulated in LBW (P < 0.05 vs. |
| 445 | 21436455 | The effects of FGF19 are independent of the activity of either insulin or the protein kinase Akt and, instead, are mediated through a mitogen-activated protein kinase signaling pathway that activates components of the protein translation machinery and stimulates glycogen synthase activity. |
| 446 | 21088934 | To investigate insulin sensitivity within the liver, serine phosphorylation of IRS-1 (Ser307) and Akt (Ser473) and expression of gluconeogenic genes, PEPCK and G6Pase, were tested. |
| 447 | 21088934 | In the diabetic (DM) group, IRS-1 phosphorylation was increased (P < 0.05), Akt phosphorylation was reduced (P < 0.05), expression of PEPCK and G6Pase was elevated (P < 0.05), and ER stress markers were up-regulated (P < 0.05) relative to the non-diabetic rats. |
| 448 | 21228321 | Furthermore, data indicate that protein kinase B activation is involved in the stabilization of GLUT1 at the plasma membrane. |
| 449 | 21497580 | When applied at doses of 1 ?M, only selenite and MSeA were capable of delaying insulin-induced phosphorylation of protein kinase B (Akt) and attenuating insulin-induced phosphorylation of forkhead box class O transcription factors FoxO1a and FoxO3. |
| 450 | 15964918 | Apoptosis increased significantly in HUVEC exposed to 40 mM d-glucose. d-Glucose at 40 mM significantly decreased tyrosine-phosphorylated PI3k, threonine 308-phosphorylated-Akt, and Akt activity relative to control 5 mM d-glucose. |
| 451 | 21426932 | Plasmid-derived overexpression as well as downregulation of DJ-1 by siRNA showed the requirement of this protein in high glucose-stimulated Akt phosphorylation. |
| 452 | 21460183 | The increased superoxide content induces c-Jun N-terminal kinase 1 (JNK1) kinase activity, which in turn affects FOXO localization through a compensatory dephosphorylation of Akt. |
| 453 | 21573155 | Using human dermal fibroblasts cultured on 3DG-collagen as a model of diabetic wounds, we demonstrated that p38 MAPK can promote either cell growth or cell death, and this was dependent on the activation of AKT and ERK1/2. |
| 454 | 21573155 | Wound closure on native collagen was dependent on p38 MAPK phosphorylation of AKT and ERK1/2. |
| 455 | 21573155 | Furthermore, proliferation and collagen production in fibroblasts cultured on native collagen was dependent on p38 MAPK regulation of AKT and ERK1/2. |
| 456 | 21354306 | Since Akt promotes cell survival at least partially via phosphorylation and inhibition of downstream forkhead box-O (FoxO) transcription factors, we generated neuroblastoma cells stably overexpressing a dominant negative mutant of FoxO1 mimicking activation of the insulin/IGF-1 pathway on FoxO-mediated transcription. |
| 457 | 19139117 | The phosphatidylinositol 3-kinase (PI3K)/Akt signaling cascade is an important component of the insulin signaling in normal tissues leading to glucose uptake and homeostasis and for cell survival signaling in cancer cells. |
| 458 | 21396911 | Concomitant to the impairment of ISGU, iAs³(+) exposure significantly attenuated insulin-stimulated intracellular ROS accumulation and AKT S473 phosphorylation, which could be attributed to the activation of NRF2 and induction of a battery of endogenous antioxidant enzymes. |
| 459 | 21502318 | We found that phosphorylation of I2PP2A was associated with rapid and transient inhibition of a ?-arrestin 2-associated pool of protein phosphatase 2A, leading to activation of Akt and increased phosphorylation of glycogen synthase kinase 3? in an arrestin signalsome complex. |
| 460 | 20299475 | The robust induction of the gluconeogenic program in liver of rapamycin-treated rats underlies the development of severe glucose intolerance even in the face of preserved hepatic insulin signaling to Akt and despite a modest reduction in adiposity. |
| 461 | 20393162 | We found that a 1-h palmitate incubation in lean myotubes reduced (P < 0.05) insulin-stimulated phosphoprotein kinase B (Akt), Akt substrate 160 (AS160), and inhibitory factor kappaBalpha (IkappaBalpha) mass, all of which were prevented with AICAR inclusion. |
| 462 | 21453786 | In addition, in conditions of insulin resistance, i.e., preceding the onset of type 2 diabetes, the phosphatidylinositol (PI) 3-kinase (PI3K)/Akt pathway is selectively inhibited, while the mitogen activated protein (MAP)-kinase pathway remains largely unaffected, thus allowing compensatory hyperinsulinemia to elicit pro-atherogenic events in vascular smooth muscle and endothelial cells, including increased cell proliferation, and the expression of plasminogen activator inhibitor-1, as well as of proinflammatory cytokines and endothelial adhesion molecules. |
| 463 | 21655268 | Moreover, we found that exendin-4 treatment increased hepatic AKT and FOXO1 phosphorylation and inhibited glucose-6-phosphotase (G6P) and Phosphoenolpyruvate carboxykinase (PEPCK) expression in young mice, but this effect was attenuated in aging mice while the insulin sensitivity showed no change in the young group but significantly improved in aging mice. |
| 464 | 21497640 | The pongamol-induced increase in GLUT4 translocation was completely abolished by wortmannin, and pongamol significantly potentiated insulin-mediated phosphorylation of AKT (Ser-473). |
| 465 | 21497640 | We conclude that pongamol-induced increase in glucose uptake in L6 myotubes is the result of an increased translocation of GLUT4 to plasma membrane, driven by a PI-3-K/AKT dependent mechanism. |
| 466 | 20938440 | Treatment of adipocytes and hSkMC with PEDF induced insulin resistance in adipocytes, skeletal and smooth muscle cells at the level of insulin-stimulated Akt phosphorylation, which was dose dependent and more prominent in adipocytes. |
| 467 | 21674027 | DLBS3233 was also found to enhance the expression of genes associated with increased insulin signaling and sensitivity, such as peroxisome proliferator-activated receptor gamma, phosphatidylinositol-3 kinase, Akt, and glucose transporter 4. |
| 468 | 20383279 | This hypothesis was confirmed by the ability of Ang II to induce tyrosine nitration of the MAP kinases ERK1/2 and of protein kinase B/Akt (Akt). |
| 469 | 20383279 | Inhibition of nitric oxide synthase and NAD(P)Hoxidase and scavenging of free radicals with myricetin restored insulin-stimulated Akt phosphorylation and GLUT4 translocation in the presence of Ang II. |
| 470 | 20383279 | Similar restoration was obtained by inhibiting the ERK activating kinase MEK, indicating that these kinases regulate Akt activation. |
| 471 | 21309058 | In isolated extensor digitorum longus muscle, FGF21 potentiated insulin-stimulated glucose transport, without altering phosphorylation of Akt or AMP-activated protein kinase. |
| 472 | 21527748 | Exposure to acrolein blocked vascular endothelial growth factor (VEGF)/AMD3100-stimulated mobilization of Flk-1(+)/Sca-1(+) but not Sca-1(+)-only cells and prevented VEGF-induced phosphorylation of Akt and endothelial nitric oxide synthase in the aorta. |
| 473 | 20455996 | Both drugs affected signalling in the protein kinases B (AKT)/mammalian target of rapamycin pathway; metformin activated adenosine monophosphate (AMP)-activated protein kinase whereas rosiglitazone increased chromosome ten level. |
| 474 | 21646544 | Transient down-regulation and overexpression of Akt isoforms in adipocytes demonstrated that insulin-activated PI3-kinase signals to GLUT4 primarily through Akt2 kinase, whereas Akt1 and Akt2 signal to FoxO1. |
| 475 | 21646544 | We propose that the lower threshold of insulin activity for FoxO1's nuclear exclusion is in part due to its regulation by both Akt isoforms. |
| 476 | 21487310 | Intranasal delivery of insulin was associated with greater preservation of the phosphatidylinositol 3-kinase signaling pathway involving Akt, cyclic AMP response element binding protein,and glycogen synthase kinase 3? but did not alter extracellular signal-regulated kinase, mitogen-activated protein kinase/extracellular signal-regulated kinase, or c-Jun amino-terminal kinase. |
| 477 | 16897074 | Myotubes from type 2 diabetic patients displayed marked reduction in the effects of insulin on glycogen synthesis and on PKB phosphorylation. |
| 478 | 19259639 | Protection against diet-induced insulin resistance in Elovl6 (-/-) mice is partially due to restoration of hepatic insulin receptor substrate-2 and suppression of hepatic protein kinase C epsilon, resulting in restoration of Akt phosphorylation. |
| 479 | 20107192 | The phosphoinositide-3-kinase inhibitor LY294002 and dominant-negative Akt inhibited antiapoptotic action of BFT-induced and Pim-1 upregulation in high glucose-challenged cardiomyocytes. |
| 480 | 21447785 | Diabetic Ins2(+/Akita):apoE(-/-) mice exhibited diminished VLDL secretion by ~50%, which was accompanied by blunted Akt phosphorylation in response to insulin infusion and decreased triglyceride content in the liver. |
| 481 | 21505148 | Multiple kinases, including Akt and AMPK, phosphorylate TBC1D1 and AS160 on distinct residues, regulating their activity and allowing for GLUT4 translocation. |
| 482 | 21684255 | Treatment of TRPC3(+/+) macrophages with the pro-apoptotic cytokine TNF? induced time-dependent phosphorylation of I?B?, AKT and BAD, and this was drastically reduced in TRPC3(-/-) macrophages. |
| 483 | 16198623 | Moreover, leptin augmented PDGF-dependent proliferation of HSCs by enhancing downstream intracellular signaling pathways via mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3 kinase (PI3K)/Akt. |
| 484 | 16951716 | Cell viability was measured by Trypan Blue exclusion and the response to insulin evaluated by the activation of the extracellular regulated kinase (ERK1/2), ERK kinase (MEK1/2) and protein kinase B (PKB/Akt) signaling components. |
| 485 | 19709445 | The IL-8 inhibited insulin-induced Akt phosphorylation. |
| 486 | 19709445 | These data suggest that IL-8 is a main adipocytokine producing insulin resistance via the inhibition of insulin-induced Akt phosphorylation in adipocytes. |
| 487 | 19897600 | Although IGFBP5 is identified as a gene induced by Akt1 activation in the beta-cell, Igfbp5 expression is not necessary for myrAkt1 to augment beta-cell size or mass in vivo. |
| 488 | 21320485 | Decreased PTEN and increased phospho-Akt were found in kidney of diabetic rats, and in vitro research revealed that high glucose attenuated PTEN expression in a time-dependent manner, concomitant with activation of Akt. |
| 489 | 21412813 | In cultured hepatocytes, PANDER overexpression induced lipid deposition, increased FOXO1 expression, and suppressed insulin-stimulated Akt activation and FOXO1 inactivation. |
| 490 | 18323518 | By regulating VEGFR2 expression and activation, PKC-epsilon expression is critical for activation of Akt and eNOS by VEGF and contributes to VEGF-stimulated Erk activation, whereas PKC-alpha has opposite effects. |
| 491 | 21754917 | Additionally, Akt activation and neurite outgrowth in response to insulin were significantly decreased in DRG cultures from diabetic ob/ob mice. |
| 492 | 21255808 | The effects of GLP-1 and/or candesartan on glucolipotoxicity-induced apoptosis and the phosphorylation of insulin receptor substrate-2 (IRS-2), protein kinase B (PKB), and forkhead box O1 (FoxO1) were evaluated by using MIN6 cells and isolated mouse pancreatic islets. |
| 493 | 21677282 | ET-1 decreased insulin-stimulated Akt phosphorylation and increased phosphorylation of insulin receptor substrate-1 serine 636. |
| 494 | 20103705 | Liver insulin resistance was associated with a robust induction of hepatic iNOS, reduced tyrosine phosphorylation of insulin receptor (IR) beta, insulin receptor substrate (IRS)-1, and IRS-2 but elevated serine phosphorylation of IRS proteins as well as decreased Akt activation. |
| 495 | 20446576 | Since insulin regulates the eNOS activity through the phosphorylation by AKT, insulin resistance is one of major factors associating with the endothelial dysfunction in obesity and diabetes. |
| 496 | 21625639 | Importantly, increasing SPHK1 expression in glioma cells markedly elevated Akt activity and phosphorylated inactivation of FOXO3a, which led to downregulation of Bim. |
| 497 | 17351147 | Insulin improved Akt phosphorylation in the EX group and increased mTOR/S6 kinase 1 phosphorylation and muscle protein synthesis (EX group: 49 +/- 11 to 89 +/- 23; CTRL group: 58 +/- 8 to 57 +/- 12 nmol x min(-1) x 100 ml leg(-1)) in the EX group only (P < 0.05). |
| 498 | 20197055 | Thus, deletion of p110alpha in liver results in markedly blunted insulin signaling with decreased generation of PIP(3) and loss of insulin activation of Akt, defects that could not be rescued by overexpression of p110beta. |
| 499 | 21613227 | Overexpression of miR-21 mimicked the action of high glucose, which included a reduction in PTEN expression and a concomitant increase in Akt phosphorylation. |
| 500 | 21233843 | Herein, we show that transforming growth factor ?-activated kinase 1 (TAK1) directly regulates stem cell factor (SCF) expression, which activates the protein kinase B (PKB)? pro-survival pathway in a cell-autonomous manner to protect keratinocytes from ROS-mediated cell death. |
| 501 | 21620960 | We have a very good understanding of the mechanisms by which Akt isoforms are activated by growth factors and other extracellular stimuli as well as by oncogenic mutations in key upstream regulatory proteins including Ras, PI3-kinase subunits and PTEN. |
| 502 | 21572010 | Akt (at Thr(308)) phosphorylation and eNOS (at Ser(1177)) phosphorylation, and also the ?-arrestin2 protein level, were markedly decreased in the membrane fraction of insulin-stimulated ob/ob aortas (vs. insulin-stimulated lean ones). |
| 503 | 12000720 | When endogenous VEGF bioactivity was inhibited with a soluble Flt-1/Fc chimera, retinal Akt kinase activity was significantly reduced in vivo. |
| 504 | 21315178 | Particular attention is given to the role of ATM in insulin signaling and Akt activation. |
| 505 | 21697492 | It was unlikely that the decreased level of FoxO1 phosphorylation was mediated through Akt inactivation, as we observed an increased phosphorylation of Akt at Ser473 in HCV-infected cells compared to control cells. |
| 506 | 21586562 | In cultured adipocytes, recombinant Angptl2 increased adiponectin expression and stimulated insulin sensitivity partially by reducing the levels of tribbles homolog 3, a specific Akt kinase inhibitory protein. |
| 507 | 21647634 | After the application of anti-STEAP4 antibodies at 0.002 mg/mL, adipocytes exhibited reduced insulin-stimulated glucose transport by attenuating the phosphorylation of IRS-1, PI3K (p85), and Akt. |
| 508 | 21647634 | In conclusion, (i) STEAP4 regulates the function of IRS-1, PI3K, and Akt and decreases insulin-induced GLUT4 translocation and glucose uptake; (ii) ROS-related mitochondrial dysfunction may be related to a reduced IRS-1 correlation with the PI3K signaling pathway, leading to insulin resistance. |
| 509 | 21514684 | Furthermore, EGCG treatment reversed IH-induced: (1) decrease in Thr172 phosphorylation of AMP activated protein kinase (AMPK); (2) increase in protein kinase C?(PKC?) membrane translocation and Ser307 phosphorylation of insulin receptor substrate-1 (IRS-1); (3) decrease in Ser473 phosphorylation of Akt and Glucose transporter 4 (GLUT4) translocation in skeletal muscle and adipose tissue. |
| 510 | 21519329 | OSM in turn attenuated insulin-dependent Akt activation and, as a downstream target, glucokinase induction in hepatocytes, most likely by inducing suppressor of cytokine signaling 3 (SOCS3). |
| 511 | 21606676 | Importantly, preventing the virus Akt-imposter from triggering mTORC1 inhibited viral growth, suggesting a new way to block herpes simplex virus. |
| 512 | 21567076 | These results suggest that insulin-deficiency in IDDM decreases osteoblastogenesis associated with inhibition of Wnt signaling through the increased expression of Sost and Dkk1 and the inhibition of Akt activation. |
| 513 | 21549192 | Treatment of TR-iBRB2 cell with IGF-1 (100ng/ml for 0-24h) increases phosphorylation of (i) Akt Thr308, and its substrates including GSK-3? at Ser9, which inactivates its kinase function, and (ii) CREB at Ser133 (activation). |
| 514 | 21729007 | In addition, immunostaining and Western blot analyses revealed that impaired angiogenic response in V mice occurred in association with reduced VEGF (vascular endothelial growth factor) production and decreased eNOS (endothelial nitric oxide synthase) and Akt (also called protein kinase B) phosphorylation. |
| 515 | 21567300 | The interaction of SDF-1 with its receptor on alphaTC1 cells activated protein kinase Akt, stimulated cell proliferation and induced the expression of prohormone convertase 1/3 and the consequent production of GLP-1 in alpha cells. |
| 516 | 11375341 | Insulin stimulation of phosphatidylinositol 3-kinase activity and phosphorylation of protein kinase B were not decreased by indinavir. |
| 517 | 21813561 | Thus, our study demonstrated that Notch1 signaling protects cells from PARP- and NF-?B-induced apoptosis under high glucose through the activation of Akt. |
| 518 | 21777645 | Peroxisome proliferator-activated receptor (PPAR) ligands are reported to activate the phosphatidylinositol 3-kinase (PI3K)/Akt pathway, including pioglitazone, which belong to the thiazolidinedione (TZD). |
| 519 | 21725771 | Mechanisms identified include inhibition of MMP-9, activation of Akt, and increased expression of proangiogenic growth factors. |
| 520 | 21478266 | Inhibition of phosphoinositide 3 kinase (PI3K) activity, but not AKT, diminished both basal and TGF-?1-mediated monocyte motility. |
| 521 | 21886796 | Glucose uptake and Akt-Ser473 activation but not AMPK-? were diminished in SR-BI knock-down 3T3-L1 cells. |
| 522 | 20619819 | Elevated AKT or TOR activity lengthens circadian period, whereas reduced AKT signaling shortens it. |
| 523 | 21673100 | The addition of a specific AKT inhibitor or expression of an AKT1 short hairpin RNA inhibited AMPK S485 phosphorylation, and it attenuated the IGF-I-induced decrease in AMPK T172 phosphorylation. |
| 524 | 21693679 | Further, ApoCIII caused degradation of the nuclear factor ?B-inhibitor inhibitor of ?B and stimulated Ser473-phosphorylation of the survival serine-threonine kinase Akt. |
| 525 | 21693679 | Inhibition of the Akt signaling pathway by the phosphatidylinositol 3 kinase inhibitor LY294002 counteracted the antiapoptotic effect of ApoCIII on cytokine-induced apoptosis. |
| 526 | 21693679 | We conclude that ApoCIII in the presence of T1D-relevant proinflammatory cytokines reduces rat pancreatic islet cell apoptosis via Akt. |
| 527 | 20370652 | The ability of SIRT1 to avert apoptosis employs the activation of protein kinase B (Akt1), the post-translational phosphorylation of the forkhead member FoxO3a, the blocked trafficking of FoxO3a to the nucleus, and the inhibition of FoxO3a to initiate a "pro-apoptotic" program as shown by complimentary gene knockdown studies of FoxO3a. |
| 528 | 20370652 | Our work identifies vascular SIRT1 and its control over early apoptotic membrane signaling, Akt1 activation, post-translational modification and trafficking of FoxO3a, mitochondrial permeability, Bad activation, and rapid caspase induction as new avenues for the treatment of vascular complications during DM. |
| 529 | 21816162 | Human CETP expression increased cellular cholesterol levels and enhanced insulin-stimulated Akt phosphorylation and glucose uptake in adipocytes. |
| 530 | 21907143 | The protein kinase B(?) (Akt2) pathway is known to mediate insulin-stimulated glucose transport through increasing glucose transporter GLUT4 translocation from intracellular stores to the plasma membrane (PM). |
| 531 | 21912612 | Plasma and cardiac APN levels were decreased in diabetic rats accompanied by decreased cardiac APN receptor 2 (AdipoR2), reduced phosphorylation of Akt, signal transducer and activator of transcription 3 (STAT3) and endothelial nitric oxide synthase (eNOS) but increased IL-6 and TNF-? (all P<0.05 vs. |
| 532 | 21624038 | In contrast, oxidative stress induced by A? can be antagonized by active Akt that, in turn, inhibits Foxo3a, a pro-apoptotic transcription factor activated by reactive oxygen species generation. |
| 533 | 21762740 | We also demonstrated that apelin treatment normalizes the diabetes induced alteration of AKT and ERK activations in the pancreas of Akita mice. |
| 534 | 21810948 | More importantly, acute insulin stimulation after chronic insulin treatment resulted in blunted phosphorylation of Akt, p70S6K, and glycogen synthase kinase-3?. |
| 535 | 21810948 | Interestingly, when the cells were treated with phosphatidylinositol 3-kinase pathway inhibitor, but not MAPK pathway inhibitor, chronic insulin treatment did not block acute insulin treatment-induced Akt phosphorylation. |
| 536 | 21846802 | Adiponectin treatment inhibited NIK-induced NF-?B activation and restored insulin sensitivity by restoring PI3 kinase activation and subsequent Akt phosphorylation. |
| 537 | 19521344 | Consistent with impaired insulin signaling, we found that insulin-stimulated 3T3-L1 adipocytes exhibited decreased IRS-1(Tyr) phosphorylation, increased IRS-1(Ser) phosphorylation, and impaired Akt phosphorylation when treated with 12/15-LO product. |
| 538 | 19657716 | Further studies using RECs transfected with constitutively active and dominant-negative forms of Akt suggest that PEDF could inhibit VEGF- and also Epo-induced angiogenesis by disruption of PI3K/Akt signaling. |
| 539 | 18653708 | Insulin replacement prevented the decrease in IRS-1/Akt phosphorylation, the increase in proteolysis, and attenuated the increase in ubiquitin mRNA. |
| 540 | 18653708 | We conclude that insulinopenia accelerates proteolysis in cardiac muscle by reducing IRS-1/Akt signaling, which leads to activation of the ubiquitin-proteasome proteolytic pathway. |
| 541 | 18728232 | Insulin-resistant macrophages showed attenuated Akt activation and increased nuclear localization of FoxO1 during endoplasmic reticulum stress induced by free cholesterol loading. |
| 542 | 18840766 | An additional purpose of this study was to determine whether the changes in Bax to Bcl-2 binding corresponded to decreases in Akt signaling in palmitate-treated myoblasts. |
| 543 | 18840766 | This experiment evaluated whether temporal Akt activity coincided with Bax to Bcl-2 binding. |
| 544 | 18840766 | In addition, there was a fourfold reduction in Bax to Bcl-2 binding with palmitate treatment, which mirrored the reduction in Akt(Ser473) phosphorylation. |
| 545 | 19423845 | Thus, CRP inhibits eNOS stimulation by insulin via FcgammaRIIB and its ITIM, SHIP-1 activation, and resulting blunted activation of Akt. |
| 546 | 21568903 | PDK1 activates a large number of proteins, including Akt, some PKC isoforms, S6K and SGK. |
| 547 | 21571071 | The phosphorylation of Akt at Thr³?? was significantly normalized and the phosphorylation of eNOS at Ser¹¹?? tended to be increased by GRK2-inhibitor in the clonidine-stimulated diabetics. |
| 548 | 17667983 | Exposure to AGE-BSA was associated with Akt dephosphorylation and FOXO4 transcriptional activation leading to an increase in the expression of an effector protein of apoptosis, Bim. siRNA for FOXO4 abolished AGE-BSA-induced apoptosis of podocytes. |
| 549 | 21960994 | Expression of insulin-signaling molecules Akt, PTEN, GSK3?, and eNOS receptors for short-chain fatty acids GPR41, and GPR43 as well as protein phosphatase PP2AA, PP2AB, PP2C were evaluated using Western blot analysis. |
| 550 | 21831968 | Effects were not triggered by leptin deficiency but involved a decreased Akt phosphorylation. |
| 551 | 21937027 | Although palmitate did not impair insulin signaling as shown by the immunoblotting analysis of AKT phosphorylation, it did inactivate AMP-activated protein kinase (AMPK). |
| 552 | 20880397 | However, these PI3K inhibitors all abolished insulin-induced Na(+) absorption and inactivated PI3K, SGK1 and PKB fully. |
| 553 | 20880397 | GSK650394A and Akti-1/2 also inhibited insulin-evoked Na(+) absorption and while GSK650394A inhibited SGK1 without affecting PKB, Akti-1/2 inactivated both kinases. |
| 554 | 21861178 | Non-cytotoxic MGO concentrations inhibited insulin-induced IRS tyrosine phosphorylation and phosphatidylinositol 3-kinase (PI3K)/protein kinase B (PKB) pathway activation independently from reactive oxygen species (ROS) production. |
| 555 | 21622158 | In vitro, BDNF and CNTF expressions were stimulated by EPO through both extracellular signal-regulated kinase1/2 (ERK1/2) and Akt pathways. |
| 556 | 21982711 | Two forkhead transcription factors, FoxA2 and FoxO1, have been suggested to function downstream of and to be negatively regulated by Akt and are proposed as key determinants of hepatic triglyceride content. |
| 557 | 15182363 | Depletion of cholesterol from the cells using beta-cyclodextrin blocked insulin stimulation of glucose uptake, insulin inhibition of perilipin phosphorylation in response to isoproterenol, and insulin stimulation of protein kinase B and Map-kinases extracellular signal-related kinase (ERK)1/2 phosphorylation. |
| 558 | 17582297 | Our results suggest that reduced NO concentration and expression as well as reduced PI3K-, PKB-, and eNOS mRNA expressions might contributed to the reduced EDVR function and related pathological ultrastructure changes in IR and DM rats. |
| 559 | 21277185 | BM supplementation significantly increased IRS-2, IR ?, PI 3K and GLUT4 protein abundance in skeletal muscle, as well as phosphorylation of IRS-1, Akt1 and Akt2 when compared with HFD (P<.05 and P<.01). |
| 560 | 21532616 | Despite continued expression of Akt2 or Akt3, pAkt levels were decreased and there was evidence of reduced Akt effect on p27 in the PVPV-Akt1KO thyroids. |
| 561 | 21724864 | In contrast, Akt, PKA, PKG, and Src, other kinases known to activate eNOS, were unaffected. |
| 562 | 11113178 | IRS-3- or IRS-4-overexpressing cells showed an increase in basal phosphatidylinositol 3-kinase activity and basal Akt phosphorylation, while the IGF-1-stimulated levels correlated well with total tyrosine phosphorylation level of all IRS proteins in each cell line. |
| 563 | 12606503 | Coexpression of FKHR stimulates the PGC-1 promoter activity via interaction with the IRSs, while coexpression of FKHR (3A), in which the three putative PKB sites in FKHR are mutated, mainly abolishes the suppressive effect of PKB. |
| 564 | 12606503 | These results indicate that signaling via PKB to FKHR can partly account for the effect of insulin to regulate the PGC-1 promoter activity via the IRSs. |
| 565 | 22026163 | Furthermore, the PI3K inhibitor LY294002 significantly abolished the anti-apoptotic effect of ibrolipim, and decreased Akt phosphorylation. |
| 566 | 18216022 | In contrast, GLP-1 agonists enhance Wnt signaling via GLP-1 receptor-mediated activation of Akt and beta cell independent of GSK3beta. |
| 567 | 21893030 | Vaspin significantly increased Akt phosphorylation and prevented the impairment of Akt phosphorylation by linoleic acid (LA) in insulin-stimulated endothelial cells, which effects were abolished by pretreatment with the PI3-kinase inhibitor, Wortmannin. |
| 568 | 12502489 | Protein kinase B (PKB) serine phosphorylation was increased sevenfold in liver of PTP1B ASO-treated mice upon insulin stimulation, while phosphorylation of PKB substrates, glycogen synthase kinase (GSK)-3alpha and -3beta, was increased more than twofold. |
| 569 | 14623899 | Replacing Ser(302) with alanine significantly reduced insulin-stimulated tyrosine phosphorylation of IRS-1 and p85 binding and reduced insulin-stimulated phosphorylation of p70(S6K), ribosomal S6 protein, and 4E-BP1; however, this mutation had no effect on insulin-stimulated Akt or glycogen synthase kinase 3beta phosphorylation. |
| 570 | 16443776 | The effect on GLUT4 but not on GLUT1 is mediated by activation of protein kinase B (PKB). |
| 571 | 16443776 | These observations suggest that SGK1 regulates GLUT1 and may contribute to or account for the PI3 kinase-dependent but PKB-independent stimulation of GLUT1 by insulin. |
| 572 | 16839840 | Insulin increased (P < .05) Akt Ser473 and GSK-3alpha/beta Ser21/Ser9 phosphorylation in both trials, with the response tending to be higher in the exercise trial. |
| 573 | 17021050 | These data indicate distinct roles for Akt-1 and Akt-2 in muscle glucose metabolism and that moderate reductions in IRS-1 expression do not result in the development of insulin resistance in skeletal muscle in vivo. |
| 574 | 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. |
| 575 | 18467435 | Prevention of atrophy by IGF-I was associated with restoration of Akt phosphorylation and beta-catenin levels. |
| 576 | 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. |
| 577 | 18534819 | The decreased ATM expression suggests that ATM is involved in the development of insulin resistance through down-regulation of Akt activity. |
| 578 | 18534819 | The role of ATM in activation of Akt was further confirmed in mouse embryonic fibroblast (MEF) A29 (ATM+/+) and A38 (ATM-/-) cells. |
| 579 | 18701453 | High glucose and high insulin augmented activation of Akt, Erk, and p70S6 kinase. |
| 580 | 18701453 | Dominant negative Akt, but not dominant negative p70S6 kinase, inhibited GSK3beta phosphorylation induced by high glucose and high insulin, suggesting Akt but not p70S6 kinase was upstream of GSK3beta. |
| 581 | 18803692 | Using an experimental model of retinal ischemia induced by transiently raise the intraocular pressure (IOP), In this study, we report the original observation that ischemic retinal ganglion cells death is associated with the transient deactivation of the pro-survival kinase Akt and activation of GSK-3beta followed, during reperfusion, by a longer lasting, PI3K-dependent, activation of Akt and phosphorylation of GSK-3beta. |
| 582 | 19292965 | The level of PI-3K and PKB and phosphorylated PKB-Ser473 expression decreased in the liver of IUGR rats, whereas the levels of GSK-3beta protein increased. |
| 583 | 19356735 | These results suggest that chronic treatment with rHuEPO attenuated renal injury beyond hematopoiesis and regulated apoptosis and eNOS expression, which might be due to the activation of Akt pathway. |
| 584 | 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. |
| 585 | 19365404 | We found that Pten loss in the pancreas causes the elevation of AKT signaling in the liver. |
| 586 | 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. |
| 587 | 19472218 | We have also shown that inhibition of tyrosine kinase activity of insulin receptor (IR) and/or insulin-like growth factor 1 (IGF1) receptor (IGFR) reverses the PLTP-induced increase in levels of phosphorylated Akt (pAkt(Thr308) and pAkt(Ser473)), suggesting that PLTP-mediated activation of the PI3K/Akt pathway is dependent on IR/IGFR receptor tyrosine kinase activity. |
| 588 | 20004975 | Effect of insulin on FcepsilonRI signaling pathways was marked by enhanced phosphorylation of Lyn, Fyn, Gab2 and Akt. |
| 589 | 20384568 | Ang II caused significant (p < 0.05) inhibition of insulin-stimulated glucose transport (39%) and decreased phosphorylation of Akt Ser(473) (37%) and glycogen synthase kinase-3beta Ser(9) (42%) without affecting phosphorylation of IRS-1 Ser(307) or p38 MAPK. |
| 590 | 20416349 | We therefore investigated in adult cardiomyocytes, if UII phosphorylates GSK-3beta and Akt, one of its upstream regulators and stabilizes beta-catenin, a GSK-3beta dependent nuclear transcriptional co-activator. |
| 591 | 21965330 | Here, using mice with a liver-specific null mutation of Sirt1, we have identified a signaling pathway involving Sirt1, Rictor (a component of mTOR complex 2 [mTorc2]), Akt, and Foxo1 that regulates gluconeogenesis. |
| 592 | 21521159 | A key downstream target of the Ras family is phosphoinositide 3-kinase (PI3K), the enzyme responsible for generation of 3-phosphorylated phosphoinositides and activation of Akt (Protein Kinase B/Akt). |
| 593 | 22008087 | A number of mechanisms have been proposed in regard to the HCV induced insulin resistance involving the upregulation of Inflammatory cytokine TNF-?, hypophosphorylation of IRS-1 and IRS-2, phosphorylation of Akt, up-regulation of gluconeogenic genes, accumulation of lipids and targeting lipid storage organelles. |
| 594 | 17878289 | Active phosphorylated prosurvival kinase Akt is increased both in the beta-cells of RIP-SDF-1 mice and in INS-1 cells treated with SDF-1 and sensitive to AMD3100. |
| 595 | 17878289 | Inhibition of AKT expression by small interfering RNA attenuates the ameliorative effects of SDF-1 on caspase-dependent apoptosis induced by thapsigargin or glucose deprivation in INS-1 beta-cells. |
| 596 | 17878289 | Specific inhibition of Akt activation by a soluble inhibitor (SH-5) reverses the anti-apoptotic effects of SDF-1 in INS-1 cells and mouse islets. |
| 597 | 17878289 | SDF-1 promotes pancreatic beta-cell survival via activation of Akt, suggesting that SDF-1 agonists may prove beneficial for treatment of diabetes. |
| 598 | 18466760 | Moreover, the enhanced glucose control in aging ASIC3(-/-) mice was associated with high baseline levels of Akt phosphorylation and high copy number of mitochondrial DNA in adipose tissues. |
| 599 | 21953448 | Treatment with LC, H(2)S, or PIP3 increased the phosphorylation of IRS1, AKT, and PKC?/? as well as GLUT4 activation and glucose utilization in HG-treated cells. |
| 600 | 21810446 | Also CCK- and TPA-induced PKC? activation produced an increment in PKC?'s direct association with AKT, RafA, RafC and Lyn. |
| 601 | 21295959 | The response to insulin was evaluated through (Ser473)AKT phosphorylation. |
| 602 | 21295959 | In both subcutaneous and visceral preadipocytes, lactoferrin (1 and 10 ?M) increased adipogenic gene expressions and protein levels (fatty acid synthase, PPAR?, FABP4, ADIPOQ, ACC and STAMP2) and decreased inflammatory markers (IL8, IL6 and MCP1) dose-dependently in parallel to increased insulin-induced (Ser473)AKT phosphorylation. |
| 603 | 21939653 | We conclude that karanjin-induced increase in glucose uptake in L6 myotubes is the result of an increased translocation of GLUT4 to plasma membrane associated with activation of AMPK pathway, in a PI-3-K/AKT-independent manner. |
| 604 | 22087313 | While insulin-receptor phosphorylation was unaffected, activation of Akt and inactivation of the downstream targets Glycogen synthase kinase 3? (Gsk3? and Forkhead box O1 (FoxO1) was inhibited in palmitate-exposed cells. |
| 605 | 22087313 | Furthermore, inhibition of PP2A by specific inhibitors increased insulin-stimulated activation of Akt and phosphorylation of FoxO1 and Gsk3?. |
| 606 | 21987107 | Both AL and VA reduced myocardial AT1R levels, without affecting AT2R levels, and increased the expression of Sirt1 and PGC-1? with increased phosphorylation of Akt and eNOS. |
| 607 | 22034225 | More importantly, GH and IGF-I synergistically activate both signal transducer and activator of transcription 5 and Akt pathways. |