Ignet

Gene Pair Information

Gene Pair: INS, PIK3CA

Related Sentences

#	PMID	Sentence
1	8386184	Activation of phosphatidylinositol-3-kinase (PI3K) is one of the earliest postreceptor events in the insulin signaling pathway.
2	8386184	Incubation of soleus muscles from lean mice with 50 nM insulin caused a 3-10-fold increase in antiphosphotyrosine-immunoprecipitable PI3K (antiPTyr-PI3K) activity within 2 min in muscle homogenates as well as both the cytosolic and membrane fractions.
3	8386184	Insulin did not affect total PI3K activity.
4	7485492	Phosphorylated IRS-1 then interacts with the p85 alpha subunit of phosphatidylinositol 3-kinase (PI3K), Nck, growth factor receptor-bound protein 2 (GRB2), and Syp, thus branching insulin's signal for both mitogenic and metabolic responses.
5	8690802	Insulin infusion induced a significant increase in the mRNA level of Glut 4 (+56 +/- 13%), Rad (+96 +/- 25%), the p85alpha subunit of phosphatidylinositol-3-kinase (+92 +/- 18%) and a decrease in the lipoprotein lipase mRNA level (-49 +/- 5%), while the abundance of the other mRNAs was unaffected.
6	10813377	Neither early steps in insulin signaling nor the phosphatidylinositol 3-kinase (PI3K) branch of this pathway were affected by TRO, because it had no effect on IRS-1 phosphorylation, PI3K/IRS-1 association, or Akt phosphorylation.
7	10751417	Compared with control cells, cells expressing high levels of PTP1B showed a 50-60% decrease in maximally insulin-stimulated tyrosyl phosphorylation of IR and insulin receptor substrate-1 (IRS-1) and phosphoinositide 3-kinase (PI3K) activity associated with IRS-1 or with phosphotyrosine.
8	10751417	Our results suggest that: 1) insulin stimulation of glucose transport in adipocytes requires
9	11274905	Insulin stimulated GS activity was found to occur via a PI-3 kinase (PI-3K)-dependent pathway as wortmannin, an inhibitor of PI-3K, blocked insulin's ability to stimulate GS activity.
10	11274905	After treatment with insulin (100 nM) for 5 min, cell extracts were assayed for IRS-1 associated and total PI-3K activity.
11	11274905	At LG, insulin increased PI-3K activity by 43%.
12	11274905	There was no insulin stimulation of PI-3K activity in cells cultured in HG or GlcN.
13	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.
14	11914736	Their DNA binding activity and their transactivating potency can be modified in response to nutrients (glucose, NEFA) or hormonal stimuli (insulin, leptin, glucagon like peptide-1, growth hormone, prolactin) through kinase-dependent signalling pathways (PI3-K, p38MAPK, PKA, CaMK) modulating their affinities for DNA and/or for each other.
15	11916922	Signaling through the phosphatidylinositol 3'-kinase (PI3K) pathway is crucial for metabolic responses to insulin, and defects in PI3K signaling have been demonstrated in type 2 diabetes.
16	11922615	However, in contrast to insulin, shikonin-stimulated glucose uptake was not strongly inhibited by wortmannin, a specific inhibitor of phosphatidylinositol 3-kinase (PI3K).
17	12663464	Recent evidence has shown that activation of phosphatidyinositol-3-kinase (PI3K) and Akt, necessary for insulin stimulation of glucose transport, is impaired in insulin resistance.
18	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.
19	12594228	A 24-h long insulin treatment desensitized the phosphoinositide 3-kinase (PI3K)/protein kinase B (PKB) and p42/p44 MAPK pathways toward a second stimulation with insulin or insulin-like growth factor-1 and led to decreased insulin-induced glucose uptake.
20	12594228	Co-treatment of cells with insulin and LY294002, while reducing total IRS-1 phosphorylation, increased its phosphotyrosine content, enhancing IRS-1/PI3K association.
21	12594228	PDK1, mTOR, and MAPK inhibitors did not block insulin-induced reduction of IRS-1, suggesting that the PI3K serine-kinase activity causes IRS-1 serine phosphorylation and its commitment to proteasomal degradation.
22	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.
23	14514640	Phosphatidylinositol 3-kinase (PI3K) activation by insulin increases sterol regulatory element-binding protein (SREBP)-1 and LDLr expression and inhibits apoB secretion in hepatocytes.
24	14514640	Insulin and naringenin induced PI3K-dependent increases in cytosolic and nuclear SREBP-1 and LDLr expression.
25	14514641	Wortmannin, a phosphatidylinositol 3-kinase (PI3K) inhibitor, decreased insulin-stimulated expression of alpha-SMA mRNA by 26% and protein by 48% but had no effect on VSMC migration.
26	12970360	Insulin-stimulated association of PI3K with IRS-1 and IRS-2, and PI3K activity were reduced by HGA in parallel with the changes in IRS tyrosine phosphorylation, while Grb2-IRS association was unchanged.
27	15254873	After insulin administration in the fast state, tyrosine phosphorylation of IR and association of IRS-2 with PI3-K were higher in the EH and CL groups than in the CH group.
28	15588682	Much like insulin, clove-mediated repression is reversed by PI3K inhibitors and N-acetylcysteine (NAC).
29	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.
30	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.
31	16087719	In cells from STZ-rats the magnitude of the above parameters was, in general, comparable to that in normal animals, with some exceptions: basal PI3K activity and lipogenesis were higher, GLP-1, Ex-4 and Ex-9 failed to modify basal lipogenesis but increased PKB activity, insulin failed to affect the activity of MAPKs and the insulin-induced glucose uptake was impaired.
32	16098829	Inactivation of ROK also reduces insulin-stimulated IRS-1 tyrosine phosphorylation and PI3K activity.
33	16105861	Insulin-stimulated glucose disposal in adipocytes is regulated by two separate and independent pathways, the PI3K pathway and the Cbl/TC10 pathway.
34	16130009	IRS-1-associated PI3K activity was stimulated by insulin three-fold in L6 myotubes.
35	16130009	Olanzapine inhibited insulin-stimulated IRS-1-associated PI3K activity in a dose-dependent manner.
36	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.
37	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.
38	16399506	Further, infusion of a PI3K inhibitor into the third cerebral ventricle of STZ-DM rats prior to peripheral insulin injection attenuated insulin-induced glucose lowering by approximately 35%-40% in both acute and chronic insulin treatment paradigms.
39	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.
40	16293713	Treatment of cells with the phosphatidylinositol 3-kinase (PI3K) inhibitors wortmannin and LY294002 [2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one] or rapamycin, an inhibitor of mammalian target of rapamycin and ribosomal p70 S6 kinase (p70S6K) phosphorylation, or with an adenovirus containing green fluorescent protein and a dominant-negative and kinase-dead Akt, effectively inhibited the insulin-mediated increase in alpha-class GST expression and GST activity toward NBD.
41	16505233	Moreover, SOCS3 is required for tumor necrosis factor-alpha full inhibition of insulin-stimulated IRS-1 and -2 phosphorylation, phosphatidylinositol 3 kinase activity, and glucose uptake.
42	16506055	Using aortic VSMC taken from humans and Zucker rats and cultured in normoxia, the following were evaluated: (1) dose-dependent (0.5, 1, 2 nmol/l) and time-dependent (2, 4, 6 h) effects exerted by insulin on HIF-1alpha content in both nucleus and cytosol, measured by Western blots; (2) insulin effects on HIF-1 DNA-binding activity on the VEGF gene, measured by electrophoretic mobility shift assay; and (3) involvement of the insulin signalling molecules in these insulin actions, by using the following inhibitors: LY294002 (PI3-K), PD98059 (extracellular signal regulated kinase [ERK]), SP600125 (Jun N terminal kinase [JNK]), SB203580 (p38 mitogen-activated protein kinase) and rapamycin (mammalian target of rapamycin), and by detecting the insulin signalling molecules by Western blots.
43	16634987	Furthermore, we show using the specific inhibitors LY294002 and PD98059 that insulin induced increased gelatinase activity via an intracellular signalling mechanism involving phosphatidylinositol-3 kinase (PI-3K) and the extracellular signal-regulated kinase 1/2 (ERK1/2) mitogen-activated protein kinases (MAPKs) respectively.
44	16870142	Insulin suppressed angptl4 mRNA expression in time- and dose-dependent manners, and the inhibitory effect was attenuated by a RNA synthesis inhibitor actinomycin D and a phosphoinositide 3-kinase (PI3K) inhibitor LY294002.
45	16794223	Thus, under conditions of PI3K activation by insulin, and to a lesser extent by the SR-BI ligand HDL, cell surface expression of SR-BI was promoted, resulting in increased SR-BI-mediated HDL selective lipid uptake.
46	17109620	Insulin stimulated glutamate-L-cysteine ligase (GCL) activity by activation of phosphatidylinositol 3-kinase (PI3K)/Akt/mTOR signaling, increased serine phosphorylation and nuclear translocation of nuclear NF-E2-related factor 2 (Nrf2), and upregulation of Nrf2-dependent GCL-catalytic (GCLc) subunit expression.
47	17109620	Inhibitors of insulin receptor tyrosine kinase, PI3K, Akt and mTOR abrogated insulin-induced Nrf2-mediated GCLc expression, redox balance, and IHEC survival.
48	17571165	Insulin resistance in these tissues was associated with reduced insulin-stimulated insulin receptor substrate 1- (IRS-1-) and IRS-2-associated PI3K activity in muscle and liver, respectively.
49	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.
50	18202124	Significant insulin-stimulated increases in PI3K activity was coimmunoprecipitated with all IRS isoforms.
51	18202124	In cells overexpressing PKC-zeta there was marked inhibition of insulin-stimulated PI3K activity associated with IRS-1, -3 and -4 but not IRS-2.
52	18202124	That is, PI3K activity associated with IRS-2 in response to insulin was similar in control cells and cells overexpressing PKC-zeta.
53	18562232	Changes in the expression of HKII and p85alpha Pi3K were examined as positive controls for the induction of gene expression by the insulin pathway.
54	19330070	The critical initial steps in insulin action include phosphorylation of adapter proteins and activation of phosphatidylinositol 3-kinase (PI3K).
55	19223652	This change in the glucose sensitivity in the presence of insulin was reversed by the phosphatidylinositol 3-kinase (PI3K) inhibitor wortmannin (10 nM) but not by the mitogen-activated kinase (MAPK) inhibitor PD-98059 (PD; 50 microM).
56	19357831	In liver, as well as in muscle, IRS-2/PI3K activation by insulin was intact, whereas IRS-1/PI3K activation by insulin was impaired.
57	19883613	PI3K signaling is thought to mediate leptin and insulin action in hypothalamic pro-opiomelanocortin (POMC) and agouti-related protein (AgRP) neurons, key regulators of energy homeostasis, through largely unknown mechanisms.
58	19914265	Results of the present study suggest that inhibition of PI3K decreases activity and memory while increasing insulin resistance, depression, and anxiety.
59	20061534	Phosphatidylinositide 3-kinases (PI3Ks) play central roles in insulin signal transduction.
60	20061534	By applying pharmacological inhibitors, transient overexpression and small-interfering RNA-based knockdown of PI3K and PKB/Akt isoforms, together with PI-lipid profiling and live-cell confocal and total internal reflection fluorescence microscopy, we now demonstrate that in response to insulin, PI3K-C2alpha generates PI(3,4)P(2), which allows the selective activation of PKBalpha/Akt1.
61	19557019	Pretreatment of cells with PI3-K inhibitor significantly (P<0.05, one-way ANOVA) suppressed the insulin-induced VEGF expression; neither pretreatment with the PKC inhibitor nor with the P42/p44 MAPK inhibitor showed an effect on the expression of VEGF at the mRNA or protein level (P>0.05, one-way ANOVA).
62	19557019	We propose that insulin may upregulate VEGF expression through the PI3-K signalling pathway in BRECs, and high glucose may attenuate insulin-induced VEGF expression by impairing PI3-K signalling pathways.
63	20577122	Finally, we assessed the role of phosphoinositol-3 kinase (PI3K) signaling pathway in mediating sympathetic activation to insulin in obesity.
64	20577122	Notably, ICV pretreatment with a PI3K inhibitor (LY294002) blocked the increase in lumbar SNA induced by ICV insulin in lean and agouti obese mice.
65	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.
66	21109194	The class IA PI3K pathway in ? cells in�vivo is important in the regulation of insulin secretion and may be a therapeutic target for type 2 diabetes.
67	21051417	This review focuses on insulin-initiated PI3K-Akt-eNOS survival signalling, with nitric oxide as an 'end effector' delivering cardioprotection in health and disease (especially in ischaemic heart disease), and highlights the impairment of this survival signalling as a key link between insulin resistance and cardiovascular disease.
68	21270272	Although U0126, an ERK inhibitor, enhanced insulin sensitivity and attenuated oxidative stress-induced insulin resistance, LY294002, an inhibitor of phosphoinositide 3-kinase (PI3K), worsened the insulin resistance.
69	21241768	Our data identify SIRT1 as a positive modulator of insulin signaling in muscle cells through PI3K, and this mechanism appears to be conserved from C. elegans through humans.
70	17567939	Tyrosine kinase inhibitor genistein and phosphatidylinositol 3-kinase (PI3K) inhibitor wortmannin blocked insulin-mediated PKC activation and GRK2 membranous translocation.
71	17567939	In conclusion, insulin-induced D1R desensitization involves PI3K, PKC, and GRK2.
72	21194385	Inhibition of the phosphatidylinositol 3-kinase (PI3-K) pathway during insulin pretreatment restored acute insulin-mediated Akt phosphorylation.
73	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.
74	21608432	We evaluated the effect of low doses of insulin (1 U/kg/day) and selenium (180 microg/kg/day) in combination on general physiological parameters, and on PI3K and GLUT4 levels in skeletal muscle of streptozotocin (STZ)-induced diabetic rats.
75	17130464	Clinical insulin resistance is associated with decreased activation of phosphatidylinositol 3'-kinase (PI3K) and its downstream substrate protein kinase B (PKB)/Akt.
76	17130464	In cultured cell lines, insulin-mediated PRAS40 phosphorylation was prevented by the PI3K inhibitors wortmannin and LY294002.
77	20197055	Together, these data indicate that the p110alpha isoform of PI3K plays a fundamental role in insulin signaling and control of hepatic glucose and lipid metabolism.
78	21368653	In diabetic rats, STAT3 activation was strongly reduced, as was postC cardioprotection, suggesting that the inability of insulin to restore postC may be attributed to diabetes-induced STAT3-mediated inhibition of PI3K signaling.
79	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.
80	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.
81	21475143	Examined were the effects of intravenously infused glucose and/or lipids on proximal ER stress sensor activation (PERK, eIF2-?, ATF4, Xbox protein 1 (XBP1s)), unfolded protein response (UPR) proteins (GRP78, calnexin, calreticulin, protein disulphide isomerase (PDI), stress kinases (JNK, p38 MAPK) and insulin signaling (insulin/receptor substrate (IRS) 1/2 associated phosphoinositol-3-kinase (PI3K)) in rat liver.
82	21586696	Results in cultured cells also showed that blunting insulin signaling by the PI3K inhibitor LY-294002 prevented fat accumulation, oxidative stress, and insulin resistance induced by the prolonged exposure to either insulin or oleate plus sera that normally contain insulin.
83	18846471	Co-incubation with insulin had no additional effect, but the cellular uptake was decreased by wortmannin and SB 203580, specific inhibitors of phosphatidylinositol 3-kinase (PI3K) and p38 mitogen-activated protein kinase (p38 MAPK), respectively.
84	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.
85	21803028	Ang-IV acts via IRAP, which couples PI3K and activates the later part of the insulin pathway.
86	21985785	Mechanistically, Sirt1 was found to be required for the deacetylation and inactivation of the transcription factor Stat3 during CR, which resulted in decreased gene and protein expression of the p55?/p50? subunits of PI3K, thereby promoting more efficient PI3K signaling during insulin stimulation.
87	21985785	Thus, these data demonstrate that Sirt1 is an integral signaling node in skeletal muscle linking CR to improved insulin action, primarily via modulation of PI3K signaling.
88	21969604	Insulin increased 14-3-3 binding to RhoGAP22 fourfold, and this effect was PI3K dependent.