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Gene Review

Insr  -  insulin receptor

Rattus norvegicus

Synonyms: IR, Insulin receptor
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Disease relevance of Insr


Psychiatry related information on Insr

  • After long-term memory consolidation following a water maze learning experience, gene expression of IR showed an up-regulation in the CA1, but a down-regulation in the CA3 region [1].
  • The insulin-resistant brain state is related to late-onset sporadic Alzheimer's disease, and alterations in the insulin receptor (IR) and its downstream phosphatidylinositol-3 kinase signalling pathway have been found in human brain [5].
  • They suggested that diets high in fat and energy and low in complex carbohydrates and a sedentary life-style lead to IR and that the associated hyperinsulinemia, hypertriglyceridemia, and glycemia lead to increased CRC risk through the growth-promoting effect of insulin or the increased availability of energy [6].

High impact information on Insr


Chemical compound and disease context of Insr


Biological context of Insr


Anatomical context of Insr

  • Here we investigated changes in long-term memory-associated expression of the IR and downstream molecules in the rat hippocampus [1].
  • IR autophosphorylation was measured in skeletal muscle after in vivo insulin stimulation (ie, during clamp) by Western blot and then retested after subsequent in vitro 0.1 to 100 nmol/L insulin stimulation (by enzyme-linked immunosorbent assay [ELISA]) [16].
  • Our results suggest that in rat adipocytes, sennidin A stimulates glucose incorporation in the phosphatidylinositol 3-kinase (PI3K)- and Akt-dependent, but in the IR/IRS1-independent manner [15].
  • It was found that insulin could bind with IR at the membrane of the neurons, and IR distribute not only on the somas, but also on the neurites [20].
  • We conclude that in vivo endothelial cells rapidly take up and concentrate insulin relative to plasma and muscle interstitium and that IGF-IR, like IR, may mediate insulin transit through endothelial cells in a process involving caveolae [21].

Associations of Insr with chemical compounds

  • In rat INS-1E beta cells, only Pklr expression was suppressed by low glucose as in islets, while Insr and Insrr were suppressed by high and increased by low glucose levels [22].
  • Our results suggest that the IR and/or IGF-IR signaling pathway may be involved in the mechanism of action of HCB [23].
  • Sections of fed liver were incubated with fluorescein-tagged anti-GLUT2 or Texas Red-tagged anti-IR [24].
  • Our results demonstrated that the increase in PTP1B expression and/or association with IR in MSG animals may contribute to the impaired insulin signaling mainly in liver and muscle [25].
  • AII increased the serine phosphorylation of both the IR beta-subunit and IRS-1 [26].

Physical interactions of Insr

  • HepG2 cells were firstly selected to be the model for methodological study, the results showed that insulin could bind with IR at the membrane of the studied cells after incubated 1 minute with the cells [20].

Enzymatic interactions of Insr

  • Analysis of the catalytic activity of partially purified rat adipocyte PTP-alpha and LAR and recombinant PTP-1B showed that all three PTPases dephosphorylate IR [27].

Regulatory relationships of Insr

  • These results demonstrate that TNF-alpha participates in obesity-related systemic insulin resistance by inhibiting the IR tyrosine kinase in the two tissues mainly responsible for insulin-stimulated glucose uptake: muscle and fat [28].
  • Insulin caused an immediate stimulation of Src and induced its physical association with both IR and PKCdelta [29].
  • Insulin receptor tyrosine kinase activity solubilized from hind limb muscle of control and streptozocin-induced diabetic (STZ-D) rats (2-3 wk) was studied with the substrates histone H2B and poly glutamic acid-tyrosine (glu-tyr) (4:1) [30].

Other interactions of Insr

  • Furthermore, beta cell expression of IGF-I receptor (Igf1r) and insulin receptor (Insr) is mandatory for several steps of insulin secretion [22].
  • Insulin receptor and IRS-1 appeared to be translocated to the nucleus in a time dependent manner by insulin whereas Akt levels remained unchanged by insulin treatment [31].
  • It is rarely reported the direct imaging on the binding of insulin with IR of neurons by microcopy system in live cells [20].
  • Protein tyrosine phosphatase 1B (PTP1B) acts as a physiological negative regulator of insulin signaling by dephosphorylating the activated insulin receptor (IR) [32].
  • There was some but less overlap of IR or IGF-IR or FITC-insulin with caveolin-1 [21].

Analytical, diagnostic and therapeutic context of Insr


  1. Insulin receptor signaling in long-term memory consolidation following spatial learning. Dou, J.T., Chen, M., Dufour, F., Alkon, D.L., Zhao, W.Q. Learn. Mem. (2005) [Pubmed]
  2. Exercise training and calorie restriction increase SREBP-1 expression and intramuscular triglyceride in skeletal muscle. Nadeau, K.J., Ehlers, L.B., Aguirre, L.E., Moore, R.L., Jew, K.N., Ortmeyer, H.K., Hansen, B.C., Reusch, J.E., Draznin, B. Am. J. Physiol. Endocrinol. Metab. (2006) [Pubmed]
  3. The juxtamembrane but not the carboxyl-terminal domain of the insulin receptor mediates insulin's metabolic functions in primary adipocytes and cultured hepatoma cells. Paz, K., Boura-Halfon, S., Wyatt, L.S., LeRoith, D., Zick, Y. J. Mol. Endocrinol. (2000) [Pubmed]
  4. Hyperinsulinemia instead of insulin resistance induces baroreflex dysfunction in chronic insulin-infused rats. Hong, L.Z., Hsieh, P.S. Am. J. Hypertens. (2007) [Pubmed]
  5. Alzheimer-like changes in protein kinase B and glycogen synthase kinase-3 in rat frontal cortex and hippocampus after damage to the insulin signalling pathway. Salkovic-Petrisic, M., Tribl, F., Schmidt, M., Hoyer, S., Riederer, P. J. Neurochem. (2006) [Pubmed]
  6. Insulin resistance and promotion of aberrant crypt foci in the colons of rats on a high-fat diet. Koohestani, N., Tran, T.T., Lee, W., Wolever, T.M., Bruce, W.R. Nutrition and cancer. (1997) [Pubmed]
  7. Insulin receptor phosphorylation may not be a prerequisite for acute insulin action. Simpson, I.A., Hedo, J.A. Science (1984) [Pubmed]
  8. Insulin receptor antiserum and plant lectins mimic the direct effects of insulin on nuclear envelope phosphorylation. Purrello, F., Burnham, D.B., Goldfine, I.D. Science (1983) [Pubmed]
  9. Neuronal SH2B1 is essential for controlling energy and glucose homeostasis. Ren, D., Zhou, Y., Morris, D., Li, M., Li, Z., Rui, L. J. Clin. Invest. (2007) [Pubmed]
  10. Central nervous system nitric oxide synthase activity regulates insulin secretion and insulin action. Shankar, R., Zhu, J.S., Ladd, B., Henry, D., Shen, H.Q., Baron, A.D. J. Clin. Invest. (1998) [Pubmed]
  11. Insulin receptor tyrosine kinase activity and substrate 1 (IRS-1) expression in human myometrium and leiomyoma. Orcy, R.B., Brum, I., da Silva, R.S., Kucharski, L.C., Corleta, H.E., Capp, E. Eur. J. Obstet. Gynecol. Reprod. Biol. (2005) [Pubmed]
  12. Vanadate, but not insulin, inhibits insulin receptor gene expression in rat hepatoma cells. Bortoli, S., Amessou, M., Collinet, M., Desbuquois, B., Lopez, S. Endocrinology (1997) [Pubmed]
  13. Fructose-fed rats are protected against ischemia/reperfusion injury. Jordan, J.E., Simandle, S.A., Tulbert, C.D., Busija, D.W., Miller, A.W. J. Pharmacol. Exp. Ther. (2003) [Pubmed]
  14. Differential regulation of insulin resistance and hypertension by sex hormones in fructose-fed male rats. Vasudevan, H., Xiang, H., McNeill, J.H. Am. J. Physiol. Heart Circ. Physiol. (2005) [Pubmed]
  15. Sennidin stimulates glucose incorporation in rat adipocytes. Abe, D., Saito, T., Sekiya, K. Life Sci. (2006) [Pubmed]
  16. Rats that are made insulin resistant by glucosamine treatment have impaired skeletal muscle insulin receptor phosphorylation. Spampinato, D., Giaccari, A., Trischitta, V., Costanzo, B.V., Morviducci, L., Buongiorno, A., Di Mario, U., Vigneri, R., Frittitta, L. Metab. Clin. Exp. (2003) [Pubmed]
  17. Hypoglycemic effect of Astragalus polysaccharide and its effect on PTP1B. Wu, Y., Ou-Yang, J.P., Wu, K., Wang, Y., Zhou, Y.F., Wen, C.Y. Acta Pharmacol. Sin. (2005) [Pubmed]
  18. Cellular distribution of insulin-degrading enzyme gene expression. Comparison with insulin and insulin-like growth factor receptors. Bondy, C.A., Zhou, J., Chin, E., Reinhardt, R.R., Ding, L., Roth, R.A. J. Clin. Invest. (1994) [Pubmed]
  19. Sustained activation of insulin receptors internalized in GLUT4 vesicles of insulin-stimulated skeletal muscle. Dombrowski, L., Faure, R., Marette, A. Diabetes (2000) [Pubmed]
  20. Imaging on the binding of FITC-Insulin with Insulin Receptors in cortical neurons of Rat. Luo, Y., Xu, H., Huang, K., Zhang, Z., Luo, Q., Liu, Q. Conference proceedings : ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Conference (2005) [Pubmed]
  21. The vascular endothelial cell mediates insulin transport into skeletal muscle. Wang, H., Liu, Z., Li, G., Barrett, E.J. Am. J. Physiol. Endocrinol. Metab. (2006) [Pubmed]
  22. Glucose concentration and AMP-dependent kinase activation regulate expression of insulin receptor family members in rat islets and INS-1E beta cells. Raile, K., Klammt, J., Laue, S., Garten, A., Blüher, M., Kralisch, S., Klöting, N., Kiess, W. Diabetologia (2005) [Pubmed]
  23. Hexachlorobenzene is a tumor co-carcinogen and induces alterations in insulin-growth factors signaling pathway in the rat mammary gland. Randi, A.S., Cocca, C., Carbone, V., Nuñez, M., Croci, M., Gutiérrez, A., Bergoc, R., Kleiman de Pisarev, D.L. Toxicol. Sci. (2006) [Pubmed]
  24. Insulin receptor (IR) and glucose transporter 2 (GLUT2) proteins form a complex on the rat hepatocyte membrane. Eisenberg, M.L., Maker, A.V., Slezak, L.A., Nathan, J.D., Sritharan, K.C., Jena, B.P., Geibel, J.P., Andersen, D.K. Cell. Physiol. Biochem. (2005) [Pubmed]
  25. Modulation of IR/PTP1B interaction and downstream signaling in insulin sensitive tissues of MSG-rats. Hirata, A.E., Alvarez-Rojas, F., Carvalheira, J.B., Carvalho, C.R., Dolnikoff, M.S., Abdalla Saad, M.J. Life Sci. (2003) [Pubmed]
  26. Angiotensin II inhibits insulin signaling in aortic smooth muscle cells at multiple levels. A potential role for serine phosphorylation in insulin/angiotensin II crosstalk. Folli, F., Kahn, C.R., Hansen, H., Bouchie, J.L., Feener, E.P. J. Clin. Invest. (1997) [Pubmed]
  27. Dynamics of protein-tyrosine phosphatases in rat adipocytes. Calera, M.R., Vallega, G., Pilch, P.F. J. Biol. Chem. (2000) [Pubmed]
  28. Reduced tyrosine kinase activity of the insulin receptor in obesity-diabetes. Central role of tumor necrosis factor-alpha. Hotamisligil, G.S., Budavari, A., Murray, D., Spiegelman, B.M. J. Clin. Invest. (1994) [Pubmed]
  29. Src tyrosine kinase regulates insulin-induced activation of protein kinase C (PKC) delta in skeletal muscle. Rosenzweig, T., Aga-Mizrachi, S., Bak, A., Sampson, S.R. Cell. Signal. (2004) [Pubmed]
  30. Skeletal muscle insulin-receptor kinase. Effects of substrate inhibition and diabetes. Block, N.E., Komori, K., Dutton, S.L., Robinson, K.A., Buse, M.G. Diabetes (1991) [Pubmed]
  31. Nuclear matrix association of insulin receptor and IRS-1 by insulin in osteoblast-like UMR-106 cells. Seol, K.C., Kim, S.J. Biochem. Biophys. Res. Commun. (2003) [Pubmed]
  32. Rosiglitazone ameliorates abnormal expression and activity of protein tyrosine phosphatase 1B in the skeletal muscle of fat-fed, streptozotocin-treated diabetic rats. Wu, Y., Ouyang, J.P., Wu, K., Wang, S.S., Wen, C.Y., Xia, Z.Y. Br. J. Pharmacol. (2005) [Pubmed]
  33. Regulation of insulin signalling by hyperinsulinaemia: role of IRS-1/2 serine phosphorylation and the mTOR/p70 S6K pathway. Ueno, M., Carvalheira, J.B., Tambascia, R.C., Bezerra, R.M., Amaral, M.E., Carneiro, E.M., Folli, F., Franchini, K.G., Saad, M.J. Diabetologia (2005) [Pubmed]
  34. Expression and localization of insulin receptor in rat dorsal root ganglion and spinal cord. Sugimoto, K., Murakawa, Y., Sima, A.A. J. Peripher. Nerv. Syst. (2002) [Pubmed]
  35. 14-3-3 (epsilon) interacts with the insulin-like growth factor I receptor and insulin receptor substrate I in a phosphoserine-dependent manner. Craparo, A., Freund, R., Gustafson, T.A. J. Biol. Chem. (1997) [Pubmed]
  36. Dietary protein deprivation decreases the serine phosphorylation of insulin receptor substrate-1 in rat skeletal muscle. Toyoshima, Y., Ohne, Y., Takahashi, S.I., Noguchi, T., Kato, H. J. Mol. Endocrinol. (2004) [Pubmed]
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