Ignet

Gene Information

Gene symbol: IRS2

Gene name: insulin receptor substrate 2

HGNC ID: 6126

Related Genes

#	Gene Symbol	Number of hits
1	ADFP	1 hits
2	ADIPOQ	1 hits
3	AKT1	1 hits
4	AKT2	1 hits
5	AKT3	1 hits
6	ARNT	1 hits
7	BAD	1 hits
8	BTC	1 hits
9	CASP3	1 hits
10	CISH	1 hits
11	CREB1	1 hits
12	EGF	1 hits
13	EGFR	1 hits
14	ERBB2	1 hits
15	FASLG	1 hits
16	FOXO1	1 hits
17	FOXO3	1 hits
18	GCG	1 hits
19	GCK	1 hits
20	GPBAR1	1 hits
21	GSK3B	1 hits
22	IGF1	1 hits
23	IGF1R	1 hits
24	INS	1 hits
25	INSR	1 hits
26	IRS1	1 hits
27	IRS4	1 hits
28	JUN	1 hits
29	LEP	1 hits
30	MAP2K1	1 hits
31	MAP2K6	1 hits
32	MAP2K7	1 hits
33	MAPK1	1 hits
34	MAPK8	1 hits
35	MGEA5	1 hits
36	NFATC1	1 hits
37	NOS2A	1 hits
38	PAX6	1 hits
39	PDX1	1 hits
40	PI3	1 hits
41	PIK3CA	1 hits
42	PIK3CG	1 hits
43	PIK3R1	1 hits
44	PPP1R13B	1 hits
45	PRKCA	1 hits
46	PRKCZ	1 hits
47	PTEN	1 hits
48	PTPN1	1 hits
49	PTPRN2	1 hits
50	PTPRU	1 hits
51	RNF123	1 hits
52	RPS27A	1 hits
53	SHC1	1 hits
54	SIRT1	1 hits
55	SLC2A4	1 hits
56	SLC37A4	1 hits
57	SOCS1	1 hits
58	SREBF1	1 hits
59	STAT3	1 hits
60	TCF7L2	1 hits
61	TMEM11	1 hits
62	TNF	1 hits
63	UCP2	1 hits
64	YAP1	1 hits
65	YES1	1 hits

Related Sentences

#	PMID	Sentence
1	21933986	In liver, basal IRS-2 expression is controlled via a temporal negative feedback of sterol regulatory element-binding protein 1 (SREBP-1) to antagonize transcription factors forkhead box class O (FoxO)1/FoxO3a at an insulin response element (IRE) on the IRS-2 promoter.
2	21933986	In contrast, inhibition of phosphatidylinositol 3-kinase (PI3K) or PKB significantly increased IRS-2 levels in ?-cells.
3	21933986	ChIP assays indicated that transcription factors FoxO1 and FoxO3a associated with the IRE on the IRS-2 promoter in ?-cells in a PI3K/PKB-dependent manner, whereas others, such as SREBP-1, the transcription factor binding to immunoglobulin heavy chain enhancer 3', and the aryl hydrocarbon receptor nuclear translocator (ARNT), did not.
4	21933986	However, only FoxO3a, not FoxO1, was capable of driving IRS-2 promoter activity via the IRE in ?-cells.
5	21933986	In vivo studies showed insulin was able to suppress IRS-2 expression via activation of SREBP-1 in the liver, but this mechanism was not apparent in pancreatic islets from the same animal.
6	21933986	The molecular mechanism for feedback control of IRS signaling to decrease IRS-2 expression in liver and ?-cells is quite distinct, with a predominant role played by FoxO3a in ?-cells.
7	21940781	NFATc1 translocation to the nucleus in response to glucose and association of NFATc1 to conserved NFAT binding sites in the IRS-2 promoter were demonstrated.
8	9204876	During insulin stimulation, p85 associated with pp60(IRS3) more rapidly than with IRS-1 or IRS-2.
9	9368055	In the present study, we demonstrate that IRS-2 can mediate translocation of the insulin responsive glucose transporter GLUT4 in a physiologically relevant target cell for insulin action.
10	9368055	Co-immunoprecipitation experiments performed on cell lysates derived from freshly isolated rat adipose cells incubated in the presence or absence of insulin indicated that twice as much phosphatidylinositol 3-kinase was associated with endogenous IRS-1 as with IRS-2 after insulin stimulation.
11	9368055	Our data directly demonstrate that IRS-2, like IRS-1, is capable of participating in insulin signal transduction pathways leading to the recruitment of GLUT4.
12	9399964	This results in differential decreases in IRS-1 and IRS-2 phosphorylation, docking of the p85alpha regulatory subunit of PI 3-kinase, and activation of this enzyme in these two insulin target tissues.
13	9399964	Thus, there are multiple alterations in the early steps of insulin signaling in the ob/ob mouse, with differential regulation of IRS-1 and IRS-2, various PI 3-kinase regulatory isoforms, and a lack of compensation for the decrease in insulin signaling by any of the known alternative pathways at these levels.
14	9519710	Englitazone did not increase IR, IRS-1/IRS-2, pp60, or MAPK phosphorylation, nor did it enhance insulin's stimulation of these parameters.
15	10525667	The variant did not affect the binding of IRS-2 to the insulin receptor or p85alpha of phosphatidylinositol 3-kinase when measured in the yeast two-hybrid system.
16	11162649	Intracellular pV-stimulated tyrosine phosphorylation, including that of IRS-2, was generally increased by high glucose suggesting a further inhibition of PTP and/or enhanced tyrosine kinase activity.
17	11259670	Insulin also inhibited transcription of a reporter gene driven by the human IRS-2 promoter that was transfected into freshly isolated rat hepatocytes.
18	11739098	After insulin injection, pY of the IR was not different between groups, whereas pY of IRS-1 and IRS-2 was reduced (P < 0.05) in HSD vs.
19	11739098	In addition, association of IRS-1 and IRS-2 with p85 was significantly reduced in HSD vs.
20	11812758	In wild-type (WT) mice, insulin increased IRS-2 tyrosine phosphorylation (approximately 2.5-fold) and IRS-2-associated PI 3-kinase activity (approximately 3-fold).
21	11812758	In conclusion, IRS-2 tyrosine phosphorylation and associated PI 3-kinase activity are markedly enhanced by insulin in the immediate period after exercise.
22	11812758	IRS-2 signaling can partially account for the increase in insulin-stimulated phosphotyrosine-associated PI 3-kinase activity after exercise.
23	11916925	This insulin resistance was associated with impaired insulin receptor substrate (IRS)-2-associated phosphatidylinositol 3' (PI3) kinase activation and IRS-2 tyrosine phosphorylation as well as significantly decreased protein kinase C (PKC)-zeta/lambda activation in response to insulin.
24	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.
25	11964395	Insulin-stimulated phosphorylation of the insulin receptor, insulin receptor substrate (IRS)-1, and associated phosphatidylinositol 3-kinase were normal in TG mice, whereas IRS-2 protein and phosphorylation were down-regulated compared with control mice.
26	11964395	Furthermore, these results demonstrate that PEPCK overexpression results in a metabolic pattern that increases glucose-6-phosphatase mRNA and results in a selective decrease in IRS-2 protein, decreased phosphatidylinositol 3-kinase activity, and reduced ability of insulin to suppress gluconeogenic gene expression.
27	12138086	EGF increased the tyrosine phosphorylation of several proteins (the EGF receptor, insulin receptor substrate (IRS)-1, IRS-2, and Grb2-associated binder 1), whereas Shc and Gab2 were only weakly and inconsistently phosphorylated. p85, the regulatory subunit of phosphatidylinositol 3-kinase (PI 3-kinase), was also found to associate with all of these docking molecules, showing that EGF activated PI 3-kinase pools that were additional to those of insulin.
28	12138086	Both insulin and EGF increase the tyrosine phosphorylation and activation of IRS-1 and IRS-2, whereas EGF is also capable of activating additional PI 3-kinase pools and, thus, can augment the downstream signaling of insulin in insulin-resistant states like Type 2 diabetes.
29	12228220	We show that SOCS1 or SOCS3 targeted IRS1 and IRS2, two critical signaling molecules for insulin action, for ubiquitin-mediated degradation.
30	12228220	SOCS1 or SOCS3 bound both recombinant and endogenous IRS1 and IRS2 and promoted their ubiquitination and subsequent degradation in multiple cell types.
31	12228220	Mutations in the conserved SOCS box of SOCS1 abrogated its interaction with the elongin BC ubiquitin-ligase complex without affecting its binding to IRS1 or IRS2.
32	12228220	The SOCS1 mutants also failed to promote the ubiquitination and degradation of either IRS1 or IRS2.
33	12228220	Adenoviral-mediated expression of SOCS1 in mouse liver dramatically reduced hepatic IRS1 and IRS2 protein levels and caused glucose intolerance; by contrast, expression of the SOCS1 mutants had no effect.
34	12554784	The MEK1 mutant, which activates ERK, markedly down-regulated expression of the insulin receptor (IR) and its major substrates, IRS-1 and IRS-2, mRNA and protein, and in turn reduced tyrosine phosphorylation of IR as well as IRS-1 and IRS-2 and their associated phosphatidyl inositol 3-kinase (PI3K) activity.
35	12554784	The MKK6 mutant, which activates p38, moderately inhibited IRS-1 and IRS-2 expressions and IRS-1-associated PI3K activity without exerting a significant effect on the IR.
36	12554784	Finally, the MKK7 mutant, which activates JNK, reduced tyrosine phosphorylation of IRS-1 and IRS-2 and IRS-associated PI3K activity without affecting expression of the IR, IRS-1, or IRS-2.
37	12493745	Insulin-positive beta-cells were decreased to nearly zero in IRS-2(-/-) mice with diabetes.
38	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.
39	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.
40	12941761	In myoblasts, HMR 1964 produced a minor activation of insulin receptor substrate (IRS)-1 tyrosine phosphorylation, but a prominent activation of IRS-2, with a significantly stronger effect than insulin in human myoblasts.
41	12941762	To assess the role of insulin receptor (IR) substrate (IRS)-2 in insulin action and resistance in the liver, immortalized neonatal hepatocyte cell lines have been generated from IRS-2(-/-), IRS-2(+/-), and wild-type mice.
42	12941762	The lack of IRS-2 did not result in enhanced IRS-1 tyrosine phosphorylation or IRS-1-associated phosphatidylinositol (PI) 3-kinase activity on insulin stimulation.
43	12941762	Total insulin-induced PI 3-kinase activity was decreased by 50% in IRS-2(-/-) hepatocytes, but the translocation of PI-3,4,5-trisphosphate to the plasma membrane in these cells was almost completely abolished.
44	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.
45	12941762	Reconstitution of IRS-2(-/-) hepatocytes with adenoviral IRS-2 restored activation of these pathways, demonstrating that IRS-2 is essential for functional insulin signaling in hepatocytes.
46	12941762	However, insulin was not able to suppress gluconeogenic gene expression in primary hepatocytes lacking IRS-2, but when IRS-2 signaling was reconstituted, these cells recovered this response to insulin.
47	14550282	Here we tested the hypothesis that the novel analog [LysB3, GluB29] insulin (insulin glulisine, IG) might mediate an enhanced beta-cell protective effect due to its unique property of preferential IRS-2 phosphorylation.
48	15467829	Diabetes resolved when the mice were between 6 and 10 months of age: functional beta cells expressing Irs2 repopulated the pancreas, restoring sufficient beta cell function to compensate for insulin resistance in the obese mice.
49	15467830	We conclude that, in beta cells and the hypothalamus, Irs2 is crucially involved in the regulation of beta cell mass and leptin sensitivity.
50	15711641	In many cases, insulin resistance in liver is associated with reduced expression of both major insulin receptor substrate (IRS) proteins, IRS-1 and IRS-2.
51	15711641	Decreased IRS-1 was also associated with a decrease in glucokinase expression and a trend toward increased blood glucose, whereas knockdown of IRS-2 resulted in the upregulation of lipogenic enzymes SREBP-1c and fatty acid synthase, as well as increased hepatic lipid accumulation.
52	15841180	RIPCreIrs2KO and NesCreIrs2KO mice retained leptin sensitivity, which suggests that CNS Irs2 pathways are not required for leptin action.
53	15845625	Semiquantitative RT-PCR analysis showed that insulin (10(4) microU/ml) alone or in combination with glucose (15 mm) markedly suppressed IRS-2 gene expression, whereas IRS-1 mRNA was unaffected by the culture conditions.
54	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.
55	16170201	Pten insufficiency increased peripheral insulin sensitivity in wild type and Irs2(-/-) mice and increased Akt and Foxo1 phosphorylation in the islets.
56	16179348	Troglitazone increased skeletal muscle Irs-1 and phospho-Akt levels following in vivo insulin treatment, whereas AGN194204 increased hepatic Irs-2 and insulin stimulated phospho-Akt in liver.
57	16721034	The data revealed that the administration of a high dose (0.1 mg/kg body weight/day) of DEX (HDEX) attenuated insulin signaling in the cerebral cortex and hypothalamus, whereas exercise potentiated their insulin signaling along with induction of IRS2 expression.
58	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.
59	16341686	Although insulin receptor protein level and phosphorylation were unaltered by resistin, production of IRS-1, but not IRS-2, was downregulated and a decreased tyrosine phosphorylation of IRS-1 was detected.
60	16458527	The majority of the published literature in this field suggests that IRS1 is the major substrate leading to stimulation of glucose transport in muscle and adipose tissues, whereas in liver, IRS1 and IRS2 have complementary roles in insulin signaling and metabolism.
61	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.
62	16873684	cAMP-responsive element-binding protein (CREB) is required for beta-cell survival by regulating expression of crucial genes such as bcl-2 and IRS-2.
63	17127239	Future studies are necessary to determine whether IRS2 dysfunction may promote atherosclerosis in normoglycemic, pre-diabetic patients with clinical manifestations of hyperinsulinemia and insulin resistance.
64	17952839	This reduction was associated with enhanced tyrosine phosphorylation of IRS2 and serine (473) phosphporylation of Akt, indicating improved hepatic insulin signaling.
65	17940160	Conversely, Ser phosphorylation of IRS-2 mediated by TNF-alpha activation of mitogen-activated protein kinase was the mechanism found in brown adipocytes.
66	18202124	In an in vitro kinase assay, purified recombinant PKC-zeta phosphorylated IRS-1, -3 and -4 but not IRS-2.
67	18202124	Insulin-stimulated IRS tyrosine phosphorylation was impaired by overepxression of PKC-zeta for IRS-1, -3, and -4 but not IRS-2.
68	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.
69	18202124	That is, PI3K activity associated with IRS-2 in response to insulin was similar in control cells and cells overexpressing PKC-zeta.
70	18202124	The inability of PKC-zeta to phosphorylate IRS-2 may help determine specific functional roles for IRS-2.
71	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.
72	19007436	In addition, a defect in insulin secretion could occur due to UPS-mediated degradation of IRS2 in the beta-cells of the pancreas.
73	19073770	Phogrin is involved in beta-cell growth via regulating stability of IRS2 protein by the molecular interaction with insulin receptor.
74	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.
75	19357831	Moreover, hepatic IRS-2 is known to control hepatic aPKC during insulin activation.
76	19357831	In diabetic rodent liver, diminished PKB activation may largely reflect impaired IRS-1/PI3K activation, while conserved aPKC activation reflects retained IRS-2/PI3K activity.
77	19818665	These effects appeared to be independent of IRS-2, which is directly involved in insulin action.
78	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.
79	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.
80	19965940	Decreased IRS2 attenuated the phosphorylation of Akt and, subsequently, PDX-1 protein levels were lowered in olanzapine-treated rats.
81	20547979	When expressed in cultured mouse islets, IRS-2(5A) was better than IRS-2(WT) in protecting beta-cells from apoptosis induced by a combination of IL-1beta, IFN-gamma, TNF-alpha, and Fas ligand.
82	20547979	This could be attributed to the higher transcription of Pdx1 in cytokine-treated islets that expressed IRS-2(5A).
83	20573722	In contrast, the IRS-2/MAPKs pathway is stimulated, through an activation of the IGF-IR, leading to increased Pax6 and glucagon expression.
84	18370645	More recent data on experimental atherosclerosis in the mouse shows that (1) insulin administration reduces the number and the size of atherosclerotic lesions in apo E null mice and (2) in IRS-2 null mice, the interruption in insulin signal transduction results in enhanced atherogenicity.
85	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.
86	19758361	In addition, the expression of lipogenic genes and UCP-2 were upregulated, but AMPK, IRS-2, PDX-1, GLUT-2 and Bcl-2 were downregulated in the exposed cells.
87	20947509	To examine genetically the involvement of Irs1 and Irs2 in Igf1r signaling, we generated double mutant mice lacking Igf1r specifically in pancreatic ? cells in an Irs1- or Irs2-null background.
88	20947509	We conclude that Igf1r signals primarily through Irs1 and affects insulin secretion, whereas ? cell proliferation is mainly regulated by InsR using Irs2 as a downstream signaling effector.
89	20849951	Importantly, recent studies found that ?-arrestin-1 mediates GLP-1 signalling to insulin secretion, GLP-1 antiapoptotic effect by phosphorylating the proapoptotic protein Bad through ERK1/2 activation, and PACAP potentiation of glucose-induced long-lasting ERK1/2 activation controlling IRS-2 expression.
90	20959116	Glucose-stimulated insulin secretion was enhanced in islets from male null mice as compared to male WT whereas this response in female Irs-2(-/-) islets was identical to that of female controls.
91	20959116	The ability of ?(2)-adrenoceptor (?(2)-AR) agonists to inhibit insulin secretion was attenuated in male Irs2 null mice.
92	21241768	Different SIRT1 targets have been identified, including PTP1B, AMPK, FOXO, PGC-1? and IRS2.
93	20028942	To define the relationship between these two signaling pathways in the regulation of liver metabolism, we used genetic and pharmacological approaches to study the effects of inhibiting PTP1B on hepatic insulin signaling and expression of gluconeogenic enzymes in IRS2(-/-) mice.
94	20028942	Additionally, hepatic insulin signaling was assessed in control and IRS2(-/-) mice treated with resveratrol, an antioxidant present in red wine.
95	20028942	In livers of hyperglycemic IRS2(-/-) mice, the expression levels of PTP1B and its association with the insulin receptor (IR) were increased.
96	20028942	Moreover, resveratrol treatment of hyperglycemic IRS2(-/-) mice decreased hepatic PTP1B mRNA and inhibited PTP1B activity, thereby restoring IRS1-mediated PI 3-kinase/Akt/Foxo1 signaling and peripheral insulin sensitivity.
97	20028942	By regulating the phosphorylation state of IR, PTB1B determines sensitivity to insulin in liver and exerts a unique role in the interplay between IRS1 and IRS2 in the modulation of hepatic insulin action.
98	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).
99	21459325	We show here that adiponectin upregulates IRS-2 through activation of signal transducer and activator of transcription-3 (STAT3).
100	21459325	These data have unraveled an insulin-sensitizing action initiated by adiponectin leading to upregulation of hepatic IRS-2 via an IL-6 dependent pathway through a still unidentified adiponectin receptor.
101	20466847	Genetic and biological studies have shown that reductions in IRS1 and/or IRS2 protein levels are associated with insulin resistance.
102	20466847	In this study we have shown that proteasome degradation of IRS1, but not of IRS2, is involved in HG-induced insulin resistance in Chinese hamster ovary (CHO) cells as well as in primary hepatocytes.
103	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.
104	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.
105	21541314	Jun NH2-terminal kinase (JNK) activation peaked at the lowest glucose concentration, in contrast to a progressive reduction in IRS2 protein and impairment of insulin receptor substrate signaling.
106	20501674	Our studies underscore the importance of an IR and IRS2-dependent feedback loop to keep FoxO1 activity in check for maintaining hepatic glycogen homeostasis and promoting adaptive unfolded protein response in response to altered metabolism and insulin action.
107	21354306	Overexpression of IRS-1 or IRS-2 caused complete resistance to glucose-induced caspase-3 cleavage.
108	21354306	Inhibition of PI3-kinase reversed this protective effect of IRS-1 or IRS-2.
109	21354306	Thus, overexpression of both IRS-1 and IRS-2 induces complete resistance to glucose-induced caspase-3 activation via PI3-kinase mediated BAD phosphorylation and MnSOD expression independent of FoxO1.
110	11994408	To investigate whether beta cell failure in Irs2(-/-) mice might be related to dysfunction of MODY-related transcription factors, we measured the expression of Pdx1 in islets from young Irs2(-/-) mice.
111	12488434	We report that haploinsufficiency for the forkhead transcription factor Foxo1 reverses beta cell failure in Irs2(-/-) mice through partial restoration of beta cell proliferation and increased expression of the pancreatic transcription factor pancreas/duodenum homeobox gene-1 (Pdx1).
112	21356512	In this issue of Cell Metabolism, Kubota et al. (2011) show that deletion of IRS-2 in endothelial cells in mice causes impaired transcapillary insulin transport, decreased insulin-stimulated glucose uptake in muscle, and mild glucose intolerance.
113	21356519	Moreover, restoration of insulin-induced eNOS phosphorylation in endothelial cells completely reverses the reduction in capillary recruitment and insulin delivery in tissue-specific knockout mice lacking Irs2 in endothelial cells and fed a high-fat diet.
114	21255808	Whereas palmitate significantly decreased the phosphorylation of IRS-2, PKB, and FoxO1 in MIN6 cells, these changes were significantly inhibited by treatment with GLP-1 and/or candesartan.
115	21255808	The present results suggest that GLP-1 and candesartan additively prevent glucolipotoxicity-induced apoptosis in pancreatic ?-cells through the IRS-2/phosphoinositide 3-kinase/PKB/FoxO1 signaling pathway.
116	20371624	We conclude that FOXO3a mediates a reciprocal communication between the IRS-1/PI3K/Akt and IRS-2/MEK/ERK pathways that coordinates AT-1 and ubiquitin expression during muscle atrophy.
117	21700708	The effects of iNOS on IRS-2 expression have not yet been investigated in ?-cells.
118	21700708	Here, we show that iNOS and NO donor decreased IRS-2 protein expression in INS-1/832 insulinoma cells and mouse islets, whereas IRS-2 mRNA levels were not altered.
119	21700708	Interleukin-1? (IL-1?), alone or in combination with interferon-? (IFN-?), reduced IRS-2 protein expression in an iNOS-dependent manner without altering IRS-2 mRNA levels.
120	21897861	BTC treatment increased mRNA and protein levels of insulin receptor substrate-2 (IRS-2), and this was blocked by the ErbB-1 and ErbB-2 inhibitors.
121	21897861	Inhibition of IRS-2 by siRNA blocked cell cycle progression induced by BTC treatment.
122	21897861	These results suggest that BTC exerts proliferative activity on beta cells through the activation of ErbB-1 and ErbB-2 receptors, which may increase IRS-2 expression, contributing to the regeneration of beta cells.
123	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).
124	11113178	Following transduction of IRS-3 or IRS-4, the cells showed a significant decrease in IRS-2 mRNA and protein levels without any change in the IRS-1 protein level.
125	11113178	However, IRS-3- or IRS-4-expressing cells also showed a marked decrease in IRS-1 and IRS-2 phosphorylation compared to the host cells.
126	16960890	We report that the long-term TNF-alpha pre-incubation in both parental HepG2 and HepG2-CA-Akt/PKB-alpha cells leads to the reduction in the levels of IRS-1 without altering the levels of IRS-2.
127	18538359	Thus, calcineurin inhibition decreased IRS-2 level via proteasomal IRS-2 degradation, attenuating IGF-I-induced GSK-3beta and ERK pathways.
128	20604929	Kidney-specific increases in Yes-associated protein (YAP), a key driver of organ size were also detected in the absence of Irs2.
129	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.
130	21901280	Our results indicate that TCF7L2 binds directly to multiple genes that are important in regulation of glucose metabolism in the liver, including Pck1, Fbp1, Irs1, Irs2, Akt2, Adipor1, Pdk4 and Cpt1a.
131	21984580	RESULTS In monocyte cells from human subjects with increased risk for diabetes and atherosclerosis, we found that gene expression, protein levels, and tyrosine phosphorylation of IRS2, but not InsR or IRS1, were decreased.
132	21990351	Hepatic IRS2 protein was dramatically up-regulated in mice treated with T863, possibly contributing to improved insulin sensitivity.