Gene Symbol: Irs2
Description: insulin receptor substrate 2
Alias: Irs-2, insulin receptor substrate 2, 4PS
Species: mouse
Products:     Irs2

Top Publications

  1. Kushner J, Haj F, Klaman L, Dow M, Kahn B, Neel B, et al. Islet-sparing effects of protein tyrosine phosphatase-1b deficiency delays onset of diabetes in IRS2 knockout mice. Diabetes. 2004;53:61-6 pubmed
    ..are mediated by tyrosine phosphorylation of the insulin receptor and its downstream targets, such as Irs1 and Irs2. Irs2 plays an especially important role in glucose homeostasis because it mediates some peripheral actions of ..
  2. Wei D, Tao R, Zhang Y, White M, Dong X. Feedback regulation of hepatic gluconeogenesis through modulation of SHP/Nr0b2 gene expression by Sirt1 and FoxO1. Am J Physiol Endocrinol Metab. 2011;300:E312-20 pubmed publisher
    ..Thus, our results suggest that Sirt1 can both positively and negatively regulate hepatic gluconeogenesis through FoxO1 and Nr0b2 and keep this physiological process in control. ..
  3. Li D, Yin X, Zmuda E, Wolford C, Dong X, White M, et al. The repression of IRS2 gene by ATF3, a stress-inducible gene, contributes to pancreatic beta-cell apoptosis. Diabetes. 2008;57:635-44 pubmed
    beta-Cell failure is an essential component of all types of diabetes, and the insulin receptor substrate 2 (IRS2) branch of signaling plays a key role in beta-cell survival and function...
  4. Kubota N, Kubota T, Itoh S, Kumagai H, Kozono H, Takamoto I, et al. Dynamic functional relay between insulin receptor substrate 1 and 2 in hepatic insulin signaling during fasting and feeding. Cell Metab. 2008;8:49-64 pubmed publisher
    Insulin receptor substrate (Irs) mediates metabolic actions of insulin. Here, we show that hepatic Irs1 and Irs2 function in a distinct manner in the regulation of glucose homeostasis...
  5. Ueki K, Kondo T, Kahn C. Suppressor of cytokine signaling 1 (SOCS-1) and SOCS-3 cause insulin resistance through inhibition of tyrosine phosphorylation of insulin receptor substrate proteins by discrete mechanisms. Mol Cell Biol. 2004;24:5434-46 pubmed
    ..These data indicate that SOCS-1 and SOCS-3 act as negative regulators in insulin signaling and serve as one of the missing links between insulin resistance and cytokine signaling. ..
  6. Simmgen M, Knauf C, Lopez M, Choudhury A, Charalambous M, Cantley J, et al. Liver-specific deletion of insulin receptor substrate 2 does not impair hepatic glucose and lipid metabolism in mice. Diabetologia. 2006;49:552-61 pubmed
    ..Global gene targeting in mice and in vitro studies have suggested that IRS2 mediates the physiological effects of insulin in the liver...
  7. Schubert M, Brazil D, Burks D, Kushner J, Ye J, Flint C, et al. Insulin receptor substrate-2 deficiency impairs brain growth and promotes tau phosphorylation. J Neurosci. 2003;23:7084-92 pubmed
    ..b>Irs2 signaling mediates peripheral insulin action and pancreatic beta-cell function, and its failure causes diabetes in ..
  8. Guo S, COPPS K, Dong X, Park S, Cheng Z, Pocai A, et al. The Irs1 branch of the insulin signaling cascade plays a dominant role in hepatic nutrient homeostasis. Mol Cell Biol. 2009;29:5070-83 pubmed publisher
    We used a Cre-loxP approach to generate mice with varied expression of hepatic Irs1 and Irs2 to establish the contribution of each protein to hepatic nutrient homeostasis...
  9. Kubota N, Tobe K, Terauchi Y, Eto K, Yamauchi T, Suzuki R, et al. Disruption of insulin receptor substrate 2 causes type 2 diabetes because of liver insulin resistance and lack of compensatory beta-cell hyperplasia. Diabetes. 2000;49:1880-9 pubmed
    ..These results suggest that IRS-1 and IRS-2 may play different roles in the regulation of beta-cell mass and the function of individual beta-cells. ..

More Information


  1. Burks D, Font de Mora J, Schubert M, Withers D, Myers M, Towery H, et al. IRS-2 pathways integrate female reproduction and energy homeostasis. Nature. 2000;407:377-82 pubmed
    ..elegans and Drosophila, we have identified an evolutionarily conserved mechanism in mammals that regulates both reproduction and energy homeostasis. ..
  2. Gonzalez Rodriguez A, Mas Gutierrez J, Sanz González S, Ros M, Burks D, Valverde A. Inhibition of PTP1B restores IRS1-mediated hepatic insulin signaling in IRS2-deficient mice. Diabetes. 2010;59:588-99 pubmed publisher
    Mice with complete deletion of insulin receptor substrate 2 (IRS2) develop hyperglycemia, impaired hepatic insulin signaling, and elevated gluconeogenesis, whereas mice deficient for protein tyrosine phosphatase (PTP)1B display an ..
  3. Valverde A, Fabregat I, Burks D, White M, Benito M. IRS-2 mediates the antiapoptotic effect of insulin in neonatal hepatocytes. Hepatology. 2004;40:1285-94 pubmed
    ..Epidermal growth factor, via PIP3/Akt/Foxo1 phosphorylation, was able to rescue IRS-2(-/-) hepatocytes from serum withdrawal-induced apoptosis, modulating pro- and anti-apoptotic gene expression and downregulating caspase-3 activity. ..
  4. Nagle J, Ma Z, Byrne M, White M, Shaw L. Involvement of insulin receptor substrate 2 in mammary tumor metastasis. Mol Cell Biol. 2004;24:9726-35 pubmed
    ..In contrast, IRS-1(-/-) tumor cells, which express only IRS-2, were highly invasive and were resistant to apoptotic stimuli. Collectively, our findings reveal an important contribution of IRS-2 to breast cancer metastasis. ..
  5. Kubota N, Terauchi Y, Tobe K, Yano W, Suzuki R, Ueki K, et al. Insulin receptor substrate 2 plays a crucial role in beta cells and the hypothalamus. J Clin Invest. 2004;114:917-27 pubmed
    We previously demonstrated that insulin receptor substrate 2 (Irs2) KO mice develop diabetes associated with hepatic insulin resistance, lack of compensatory beta cell hyperplasia, and leptin resistance...
  6. Huang C, Thirone A, Huang X, Klip A. Differential contribution of insulin receptor substrates 1 versus 2 to insulin signaling and glucose uptake in l6 myotubes. J Biol Chem. 2005;280:19426-35 pubmed
  7. Choudhury A, Heffron H, Smith M, Al Qassab H, Xu A, Selman C, et al. The role of insulin receptor substrate 2 in hypothalamic and beta cell function. J Clin Invest. 2005;115:940-50 pubmed
    b>Insulin receptor substrate 2 (Irs2) plays complex roles in energy homeostasis...
  8. Yi X, Schubert M, Peachey N, Suzuma K, Burks D, Kushner J, et al. Insulin receptor substrate 2 is essential for maturation and survival of photoreceptor cells. J Neurosci. 2005;25:1240-8 pubmed
    ..Here, we show that Irs2 promoted the maturation and survival of photoreceptors in the murine retina immediately after birth...
  9. Mohanty S, Spinas G, Maedler K, Zuellig R, Lehmann R, Donath M, et al. Overexpression of IRS2 in isolated pancreatic islets causes proliferation and protects human beta-cells from hyperglycemia-induced apoptosis. Exp Cell Res. 2005;303:68-78 pubmed
    Studies in vivo indicate that IRS2 plays an important role in maintaining functional beta-cell mass...
  10. Dong X, Park S, Lin X, Copps K, Yi X, White M. Irs1 and Irs2 signaling is essential for hepatic glucose homeostasis and systemic growth. J Clin Invest. 2006;116:101-14 pubmed
    Insulin receptor substrates, including Irs1 and Irs2, integrate insulin and IGF receptor signals with heterologous pathways to coordinate growth and metabolism...
  11. Kubota T, Kubota N, Moroi M, Terauchi Y, Kobayashi T, Kamata K, et al. Lack of insulin receptor substrate-2 causes progressive neointima formation in response to vessel injury. Circulation. 2003;107:3073-80 pubmed
    ..We conclude that IRS-2 is protective and retards the development of neointima formation in insulin-resistant states. ..
  12. Demozay D, Tsunekawa S, Briaud I, Shah R, Rhodes C. Specific glucose-induced control of insulin receptor substrate-2 expression is mediated via Ca2+-dependent calcineurin/NFAT signaling in primary pancreatic islet ?-cells. Diabetes. 2011;60:2892-902 pubmed publisher
    ..This insight into the IRS-2 regulation could provide novel therapeutic means in type 2 diabetes to maintain an adequate functional mass. ..
  13. Nakamura A, Togashi Y, Orime K, Sato K, Shirakawa J, Ohsugi M, et al. Control of beta cell function and proliferation in mice stimulated by small-molecule glucokinase activator under various conditions. Diabetologia. 2012;55:1745-54 pubmed publisher
    ..In addition, Irs2 knockout (Irs2 (-/-)) mice on a high-fat diet or a high-fat diet containing GKA were ..
  14. Zheng Y, Yamada H, Sakamoto K, Horita S, Kunimi M, Endo Y, et al. Roles of insulin receptor substrates in insulin-induced stimulation of renal proximal bicarbonate absorption. J Am Soc Nephrol. 2005;16:2288-95 pubmed
    ..absorption (JHCO3-) were compared in isolated renal proximal tubules from wild-type, IRS1-deficient (IRS1-/-), and IRS2-deficient (IRS2-/-) mice. In wild-type mice, physiologic concentrations of insulin significantly increased JHCO3-...
  15. Taguchi A, Wartschow L, White M. Brain IRS2 signaling coordinates life span and nutrient homeostasis. Science. 2007;317:369-72 pubmed
    ..Here, we show that, in mice, less insulin receptor substrate-2 (Irs2) signaling throughout the body or just in the brain extended life span up to 18%...
  16. Selman C, Lingard S, Choudhury A, Batterham R, Claret M, Clements M, et al. Evidence for lifespan extension and delayed age-related biomarkers in insulin receptor substrate 1 null mice. FASEB J. 2008;22:807-18 pubmed
    ..In contrast, Irs2-/- mice were short-lived, whereas Irs1+/- and Irs2+/- mice of both sexes showed normal life spans...
  17. Hanke S, Mann M. The phosphotyrosine interactome of the insulin receptor family and its substrates IRS-1 and IRS-2. Mol Cell Proteomics. 2009;8:519-34 pubmed publisher
    ..In common with other recent reports, our data furthermore hint at non-SH2 or phosphotyrosine-binding domain-mediated phosphotyrosine binding. ..
  18. Sun X, Pons S, Wang L, Zhang Y, Yenush L, Burks D, et al. The IRS-2 gene on murine chromosome 8 encodes a unique signaling adapter for insulin and cytokine action. Mol Endocrinol. 1997;11:251-62 pubmed
    ..Thus, signaling specificity through the IRS proteins may be accomplished by specific expression patterns and distinct phosphorylation patterns during interaction with various activated receptors. ..
  19. Withers D, Burks D, Towery H, Altamuro S, Flint C, White M. Irs-2 coordinates Igf-1 receptor-mediated beta-cell development and peripheral insulin signalling. Nat Genet. 1999;23:32-40 pubmed
    ..We intercrossed mice heterozygous for two null alleles (Irs1+/- and Irs2+/-) and investigated growth and glucose metabolism in mice with viable genotypes...
  20. Shimomura I, Matsuda M, Hammer R, Bashmakov Y, Brown M, Goldstein J. Decreased IRS-2 and increased SREBP-1c lead to mixed insulin resistance and sensitivity in livers of lipodystrophic and ob/ob mice. Mol Cell. 2000;6:77-86 pubmed
    ..The combination of insulin resistance (inappropriate gluconeogenesis) and insulin sensitivity (elevated lipogenesis) establishes a vicious cycle that aggravates hyperinsulinemia and insulin resistance in lipodystrophic and ob/ob mice. ..
  21. Kitamura T, Nakae J, Kitamura Y, Kido Y, Biggs W, Wright C, et al. The forkhead transcription factor Foxo1 links insulin signaling to Pdx1 regulation of pancreatic beta cell growth. J Clin Invest. 2002;110:1839-47 pubmed
    ..Mice lacking insulin receptor substrate-2 (Irs2) develop beta cell failure, suggesting that insulin signaling is required to maintain an adequate beta cell mass...
  22. Sun H, Tu X, Prisco M, Wu A, Casiburi I, Baserga R. Insulin-like growth factor I receptor signaling and nuclear translocation of insulin receptor substrates 1 and 2. Mol Endocrinol. 2003;17:472-86 pubmed
    ..The interaction of nuclear IRS proteins with upstream binding factor 1 constitutes the first direct link of these proteins with the ribosomal DNA transcription machinery. ..
  23. Withers D, Gutierrez J, Towery H, Burks D, Ren J, Previs S, et al. Disruption of IRS-2 causes type 2 diabetes in mice. Nature. 1998;391:900-4 pubmed
    ..Our results indicate that dysfunction of IRS-2 may contribute to the pathophysiology of human type 2 diabetes. ..
  24. Sadagurski M, Cheng Z, Rozzo A, Palazzolo I, Kelley G, Dong X, et al. IRS2 increases mitochondrial dysfunction and oxidative stress in a mouse model of Huntington disease. J Clin Invest. 2011;121:4070-81 pubmed publisher
    ..Reduced neuronal IGF1 or Irs2 signaling have been shown to extend life span in mice...
  25. Carew R, Sadagurski M, Goldschmeding R, Martin F, White M, Brazil D. Deletion of Irs2 causes reduced kidney size in mice: role for inhibition of GSK3beta?. BMC Dev Biol. 2010;10:73 pubmed publisher
    Male Irs2-/- mice develop fatal type 2 diabetes at 13-14 weeks. Defects in neuronal proliferation, pituitary development and photoreceptor cell survival manifest in Irs2-/- mice...
  26. Killick R, Scales G, Leroy K, Causevic M, Hooper C, Irvine E, et al. Deletion of Irs2 reduces amyloid deposition and rescues behavioural deficits in APP transgenic mice. Biochem Biophys Res Commun. 2009;386:257-62 pubmed publisher
    ..disease we crossed mice (Tg2576) over-expressing human amyloid precursor protein (APP), with insulin receptor substrate 2 null (Irs2(-/-)) mice which develop insulin resistance...
  27. Lee S, Lynn E, Kim J, Quon M. Protein kinase C-zeta phosphorylates insulin receptor substrate-1, -3, and -4 but not -2: isoform specific determinants of specificity in insulin signaling. Endocrinology. 2008;149:2451-8 pubmed publisher
    ..The inability of PKC-zeta to phosphorylate IRS-2 may help determine specific functional roles for IRS-2. ..
  28. Uchida T, Nakamura T, Hashimoto N, Matsuda T, Kotani K, Sakaue H, et al. Deletion of Cdkn1b ameliorates hyperglycemia by maintaining compensatory hyperinsulinemia in diabetic mice. Nat Med. 2005;11:175-82 pubmed
    ..p27(Kip1) progressively accumulates in the nucleus of pancreatic beta cells in mice that lack either insulin receptor substrate 2 (Irs2(-/-)) or the long form of the leptin receptor (Lepr(-/-) or db/db)...
  29. Sun H, Baserga R. Deletion of the pleckstrin and phosphotyrosine binding domains of insulin receptor substrate-2 does not impair its ability to regulate cell proliferation in myeloid cells. Endocrinology. 2004;145:5332-43 pubmed
    ..Our results also indicate that IRS-2 (either wild type or partial differentialPHPTB) is capable of inhibiting the differentiation of 32D cells. ..
  30. Neganova I, Al Qassab H, Heffron H, Selman C, Choudhury A, Lingard S, et al. Role of central nervous system and ovarian insulin receptor substrate 2 signaling in female reproductive function in the mouse. Biol Reprod. 2007;76:1045-53 pubmed
    ..To unravel the tissue-specific roles of IRS2, we examined reproductive function in female mice that lack Irs2 only in the neurons...
  31. Sharfi H, Eldar Finkelman H. Sequential phosphorylation of insulin receptor substrate-2 by glycogen synthase kinase-3 and c-Jun NH2-terminal kinase plays a role in hepatic insulin signaling. Am J Physiol Endocrinol Metab. 2008;294:E307-15 pubmed
    ..Together, our data indicate that IRS-2 is sequentially phosphorylated by JNK and GSK-3 at serines 484/488 and provide evidence for their inhibitory role in hepatic insulin signaling. ..
  32. Irvine E, Drinkwater L, Radwanska K, Al Qassab H, Smith M, O Brien M, et al. Insulin receptor substrate 2 is a negative regulator of memory formation. Learn Mem. 2011;18:375-83 pubmed publisher
    ..Insulin receptor substrate-2 (Irs2) is an adaptor protein that couples activation of insulin- and insulin-like growth factor-1 receptors to downstream ..
  33. Persaud S, Liu B, Sampaio H, Jones P, Muller D. Calcium/calmodulin-dependent kinase IV controls glucose-induced Irs2 expression in mouse beta cells via activation of cAMP response element-binding protein. Diabetologia. 2011;54:1109-20 pubmed publisher
    b>Irs2, which is upregulated by glucose, is important for beta cell plasticity...
  34. Lin X, Taguchi A, Park S, Kushner J, Li F, Li Y, et al. Dysregulation of insulin receptor substrate 2 in beta cells and brain causes obesity and diabetes. J Clin Invest. 2004;114:908-16 pubmed
    ..Here we show that a conditional knockout of insulin receptor substrate 2 (Irs2) in mouse pancreas beta cells and parts of the brain--including the hypothalamus--increased ..
  35. Dong X, COPPS K, Guo S, Li Y, Kollipara R, Depinho R, et al. Inactivation of hepatic Foxo1 by insulin signaling is required for adaptive nutrient homeostasis and endocrine growth regulation. Cell Metab. 2008;8:65-76 pubmed publisher
    ..during hepatic insulin resistance, we disrupted Foxo1 expression in the liver of mice lacking hepatic Irs1 and Irs2 (DKO mice)...
  36. Nakae J, Biggs W, Kitamura T, Cavenee W, Wright C, Arden K, et al. Regulation of insulin action and pancreatic beta-cell function by mutated alleles of the gene encoding forkhead transcription factor Foxo1. Nat Genet. 2002;32:245-53 pubmed
    ..This has been corrected in the full-text online version of the article. The name will appear correctly in the print version. ..
  37. Duan C, Li M, Rui L. SH2-B promotes insulin receptor substrate 1 (IRS1)- and IRS2-mediated activation of the phosphatidylinositol 3-kinase pathway in response to leptin. J Biol Chem. 2004;279:43684-91 pubmed
    ..protein, promotes activation of the PI 3-kinase pathway by recruiting insulin receptor substrate 1 (IRS1) and IRS2 in response to leptin...
  38. Kushner J, Ye J, Schubert M, Burks D, Dow M, Flint C, et al. Pdx1 restores beta cell function in Irs2 knockout mice. J Clin Invest. 2002;109:1193-201 pubmed
    ..In mice, the Irs2 branch of the insulin/Igf signaling system mediates peripheral insulin action and pancreatic beta cell growth and ..
  39. Cheng Z, Guo S, Copps K, Dong X, Kollipara R, Rodgers J, et al. Foxo1 integrates insulin signaling with mitochondrial function in the liver. Nat Med. 2009;15:1307-11 pubmed publisher
    ..Thus, Foxo1 integrates insulin signaling with mitochondrial function, and inhibition of Foxo1 can improve hepatic metabolism during insulin resistance and the metabolic syndrome. ..
  40. Mardilovich K, Shaw L. Hypoxia regulates insulin receptor substrate-2 expression to promote breast carcinoma cell survival and invasion. Cancer Res. 2009;69:8894-901 pubmed publisher
    ..Collectively, our results reveal a novel mechanism by which IRS-2 contributes to the aggressive behavior of hypoxic tumor cells. ..
  41. Valverde A, Burks D, Fabregat I, Fisher T, Carretero J, White M, et al. Molecular mechanisms of insulin resistance in IRS-2-deficient hepatocytes. Diabetes. 2003;52:2239-48 pubmed
    ..Suppression of gluconeogenic gene expression in IRS-2-deficient primary hepatocytes was also restored by infection with dominant negative Delta 256Foxo1. ..
  42. Long Y, Cheng Z, COPPS K, White M. Insulin receptor substrates Irs1 and Irs2 coordinate skeletal muscle growth and metabolism via the Akt and AMPK pathways. Mol Cell Biol. 2011;31:430-41 pubmed publisher
    ..process, we used muscle creatine kinase (MCK)-Cre to disrupt expression of insulin receptor substrates Irs1 and Irs2 in mouse skeletal/cardiac muscle...
  43. Garcia Barrado M, Iglesias Osma M, Moreno Viedma V, Pastor Mansilla M, Gonzalez S, Carretero J, et al. Differential sensitivity to adrenergic stimulation underlies the sexual dimorphism in the development of diabetes caused by Irs-2 deficiency. Biochem Pharmacol. 2011;81:279-88 pubmed publisher
    ..The ability of ?(2)-adrenoceptor (?(2)-AR) agonists to inhibit insulin secretion was attenuated in male Irs2 null mice. Consistent with this, the expression of the ?(2A)-AR was reduced in male Irs-2(-/-) islets...
  44. Freude S, Leeser U, Müller M, Hettich M, Udelhoven M, Schilbach K, et al. IRS-2 branch of IGF-1 receptor signaling is essential for appropriate timing of myelination. J Neurochem. 2008;107:907-17 pubmed publisher
    ..Furthermore, in neuronal/brain-specific insulin receptor knockout mice myelination was unchanged. Thus, our experiments reveal that IGF-1R/IRS-2 mediated signals are critical for appropriate timing of myelination in vivo. ..
  45. Guo S, Dunn S, White M. The reciprocal stability of FOXO1 and IRS2 creates a regulatory circuit that controls insulin signaling. Mol Endocrinol. 2006;20:3389-99 pubmed
    ..However, it is unclear why Irs2 signaling predominates in certain tissues, including pancreatic beta cells, dermal fibroblasts, photoreceptors, ..
  46. Jhala U, Canettieri G, Screaton R, Kulkarni R, Krajewski S, Reed J, et al. cAMP promotes pancreatic beta-cell survival via CREB-mediated induction of IRS2. Genes Dev. 2003;17:1575-80 pubmed
    ..Remarkably, A-CREB severely disrupted expression of IRS2, an insulin signaling pathway component that is shown here to be a direct target for CREB action in vivo...
  47. Sun X, Wang L, Zhang Y, Yenush L, Myers M, Glasheen E, et al. Role of IRS-2 in insulin and cytokine signalling. Nature. 1995;377:173-7 pubmed
    ..We purified and cloned a likely candidate called 4PS from myeloid progenitor cells and, because of its resemblance to IRS-1, we designate it IRS-2...
  48. Hennige A, Burks D, Ozcan U, Kulkarni R, Ye J, Park S, et al. Upregulation of insulin receptor substrate-2 in pancreatic beta cells prevents diabetes. J Clin Invest. 2003;112:1521-32 pubmed
    The insulin receptor substrate-2 (Irs2) branch of the insulin/IGF signaling system coordinates peripheral insulin action and pancreatic beta cell function, so mice lacking Irs2 display similarities to humans with type 2 diabetes...
  49. Tanabe K, Liu Z, Patel S, Doble B, Li L, Cras Méneur C, et al. Genetic deficiency of glycogen synthase kinase-3beta corrects diabetes in mouse models of insulin resistance. PLoS Biol. 2008;6:e37 pubmed publisher
    ..In the second model, mice missing two alleles of the insulin receptor substrate 2 (Irs2-/-), like the Ir+/- mice, are insulin resistant, but develop profound beta-cell loss, resulting ..
  50. Terauchi Y, Takamoto I, Kubota N, Matsui J, Suzuki R, Komeda K, et al. Glucokinase and IRS-2 are required for compensatory beta cell hyperplasia in response to high-fat diet-induced insulin resistance. J Clin Invest. 2007;117:246-57 pubmed
    ..DNA chip analysis revealed decreased insulin receptor substrate 2 (Irs2) expression in HF diet-fed Gck(+/-) mouse islets compared with wild-type islets...
  51. Suzuki R, Tobe K, Aoyama M, Sakamoto K, Ohsugi M, Kamei N, et al. Expression of DGAT2 in white adipose tissue is regulated by central leptin action. J Biol Chem. 2005;280:3331-7 pubmed
    ..change in the adipocytes showed that expression of DGAT2 mRNA was up-regulated in the white adipose tissue (WAT) of Irs2-/- mice, whereas that of DGAT1 was down-regulated...
  52. Masaki T, Chiba S, Noguchi H, Yasuda T, Tobe K, Suzuki R, et al. Obesity in insulin receptor substrate-2-deficient mice: disrupted control of arcuate nucleus neuropeptides. Obes Res. 2004;12:878-85 pubmed
    ..In IRS-2 KO mice, disrupted control of hypothalamic neuropeptide levels and UCP mRNA expression may contribute to the development of obesity. ..
  53. Park K, Li Q, Rask Madsen C, Mima A, Mizutani K, Winnay J, et al. Serine phosphorylation sites on IRS2 activated by angiotensin II and protein kinase C to induce selective insulin resistance in endothelial cells. Mol Cell Biol. 2013;33:3227-41 pubmed publisher
    ..insulin-induced phosphorylation of Akt/endothelial nitric oxide (eNOS) by decreasing tyrosine phosphorylation of IRS2 (p-Tyr-IRS2) in endothelial cells...