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Gene Review

Igf1  -  insulin-like growth factor 1

Rattus norvegicus

Synonyms: IGF-I, Igf-1, Insulin-like growth factor I, Somatomedin
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Disease relevance of Igf1


Psychiatry related information on Igf1

  • We tested the hypothesis that low nephron number is already present during fetal development, and the expression pattern of important molecules of the IGF system is altered in MWF rat during the critical period of kidney development [7].
  • In addition, alcohol consumption decreased IGF-I mRNA abundance in liver and muscle (approximately 50%) [8].
  • The results indicate that high-amplitude pulses of GH were nearly abolished and that concentrations of GH, IGF-I, PRL, and leptin all were suppressed by sleep deprivation [9].
  • IGF-I mRNA levels in the GH plus T group were not significantly different from those in the GH-treated group [10].
  • We wondered: a) to what extent hypoxia effects on the GH-IGF-I axis differed from those of food deprivation alone; and b) whether administration of exogenous GH mitigates alterations of the GH-IGF-I axis caused by hypoxia or food restriction [11].

High impact information on Igf1


Chemical compound and disease context of Igf1


Biological context of Igf1


Anatomical context of Igf1


Associations of Igf1 with chemical compounds

  • In comparison, HepG2 IGF binding activity was enhanced by progesterone, decreased by insulin, and unaffected by growth hormone or glucocorticoid treatment [26].
  • Two IGF-I-related proteins, IGF-II and insulin, also inhibited, but to a smaller extent, the release of nitrite and the formation of L-citrulline stimulated by IL-1 beta [27].
  • This result is consistent with prior reports indicating that the uterotrophic effects of estradiol are mediated at least in part by estradiol-stimulated uterine IGF-I gene expression [4].
  • The tyrosine 950 residue and serines 1280-1283 in the COOH terminus of the receptor are required for IGF-I-induced differentiation at 39 degrees C, although they are dispensable for IGF-I-mediated growth at 34 degrees C. Both domains have to be mutated to inactivate the differentiating function [28].
  • The early renal growth in streptozotocin (STZ)-induced diabetic rats is preceded by a transient rise in renal tissue insulin-like growth factor (IGF)-I concentration [29].
  • IGF-1 protected OPCs from TNFalpha cytotoxicity in a dose-dependent manner as measured by the XTT and TUNEL assays [30].

Physical interactions of Igf1


Enzymatic interactions of Igf1

  • However, EtOH attenuated the ability of IGF-I to phosphorylate ribosomal S6 kinase (S6K)-1 on residues T389 ( approximately 62%) and T421/S424 ( approximately 40%), and also reduced ribosomal protein S6 phosphorylation [36].
  • By comparison, IGF-I increased the levels of the phosphorylated forms of ERK-1 and -2, and Akt/PKB [37].
  • These data demonstrate that phosphorylation of IRS-1 plays an essential role in IGF-I and insulin signaling in oocyte maturation and that this effect occurs through interactions of the phosphorylated YMXM/YXXM motifs of IRS-1 with SH2 domains of PtdIns 3-kinase or some related molecules [38].
  • Muscle levels of IGF-I mRNA and phosphorylated Akt were markedly reduced in ND animals with no change following anti-TNF-alpha therapy [39].
  • Glutamate induces loss of sensitivity to IGF-I by phosphorylating the IGF-I receptor docking protein insulin-receptor-substrate (IRS)-1 in Ser(307) through a pathway involving activation of PKA and PKC in a hierarchical fashion [40].

Regulatory relationships of Igf1

  • We hypothesized that IGF-I may play a role in regulating HGF-SF activity and HCC progression [2].
  • Conversely, such negative regulation was silent in dedifferentiated VSMCs, where IGF-I activated both MAPKs via IRS-1/Grb2/Sos interaction-linked Ras activation, leading to proliferation and migration [41].
  • These results suggest that IGF-I gene expression is down-regulated by Poly(IC) treatment and that IGF-I bioavailability and action in C6 cells are also altered due to decreases in IGF-I receptor and binding protein levels [18].
  • Therefore, GH is able to activate the IGF-I/IGFBP-3 system in these cerebral cells and induce a physiological action of IGF-I [42].
  • IGF-I promotes SC survival and protects IGFBP-5 in SC-conditioned medium from proteolysis [43].

Other interactions of Igf1

  • Antiapoptotic signalling by the IGF-I receptor depended on receptor kinase activity, as cells overexpressing kinase-defective receptor mutants could not be protected by IGF-I [23].
  • IGF-I also evoked a concentration-dependent increase in the abundance of IGFBP-3 in confluent, but not sparse, SMCs without affecting IGFBP-3 mRNA [44].
  • The insulin-like growth factor, multiplication stimulating activity (MSA), and insulin were recently shown to stimulate proteoglycan synthesis in monolayer cultures of chondrocytes derived from the Swarm rat chondrosarcoma [45].
  • IGFBP-5, the most conserved of six IGFBPs characterized to date, uniquely potentiates the anabolic actions of IGF-I for skeletal cells [46].
  • Plasma IGFBP-2 was elevated and IGF-I was reduced in the nondiabetic Ax rats compared with sham Ax controls, but plasma IGFBP-3 and -4 were not significantly changed [31].

Analytical, diagnostic and therapeutic context of Igf1


  1. Hypoxia stimulates insulin-like growth factor binding protein 1 (IGFBP-1) gene expression in HepG2 cells: a possible model for IGFBP-1 expression in fetal hypoxia. Tazuke, S.I., Mazure, N.M., Sugawara, J., Carland, G., Faessen, G.H., Suen, L.F., Irwin, J.C., Powell, D.R., Giaccia, A.J., Giudice, L.C. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  2. Insulin-like growth factor I is a comitogen for hepatocyte growth factor in a rat model of hepatocellular carcinoma. Price, J.A., Kovach, S.J., Johnson, T., Koniaris, L.G., Cahill, P.A., Sitzmann, J.V., McKillop, I.H. Hepatology (2002) [Pubmed]
  3. Hormonal regulation of insulin-like growth factor II and insulin-like growth factor binding protein expression by breast cancer cells in vivo: evidence for stromal epithelial interactions. Manni, A., Badger, B., Wei, L., Zaenglein, A., Grove, R., Khin, S., Heitjan, D., Shimasaki, S., Ling, N. Cancer Res. (1994) [Pubmed]
  4. Uterotrophic actions of estradiol and tamoxifen are associated with inhibition of uterine insulin-like growth factor binding protein 3 gene expression. Huynh, H., Pollak, M. Cancer Res. (1994) [Pubmed]
  5. G beta gamma subunits mediate mitogen-activated protein kinase activation by the tyrosine kinase insulin-like growth factor 1 receptor. Luttrell, L.M., van Biesen, T., Hawes, B.E., Koch, W.J., Touhara, K., Lefkowitz, R.J. J. Biol. Chem. (1995) [Pubmed]
  6. Role of Akt/GSK-3beta/beta-catenin transduction pathway in the muscle anti-atrophy action of insulin-like growth factor-I in glucocorticoid-treated rats. Schakman, O., Kalista, S., Bertrand, L., Lause, P., Verniers, J., Ketelslegers, J.M., Thissen, J.P. Endocrinology (2008) [Pubmed]
  7. Genetic low nephron number hypertension is associated with dysregulation of the hepatic and renal insulin-like growth factor system during nephrogenesis. Rothermund, L., Nierhaus, M., Fialkowski, O., Freese, F., Ibscher, R., Mieschel, S., Kossmehl, P., Grimm, D., Wehland, M., Kreutz, R. J. Hypertens. (2006) [Pubmed]
  8. Modulation of the insulin-like growth factor system by chronic alcohol feeding. Lang, C.H., Fan, J., Lipton, B.P., Potter, B.J., McDonough, K.H. Alcohol. Clin. Exp. Res. (1998) [Pubmed]
  9. Reductions in circulating anabolic hormones induced by sustained sleep deprivation in rats. Everson, C.A., Crowley, W.R. Am. J. Physiol. Endocrinol. Metab. (2004) [Pubmed]
  10. Effect of testosterone on insulin-like growth factor-I (IGF-I) and IGF-I receptor gene expression in the hypophysectomized rat. Phillip, M., Palese, T., Hernandez, E.R., Roberts, C.T., LeRoith, D., Kowarski, A.A. Endocrinology (1992) [Pubmed]
  11. Effect of growth hormone therapy in mitigating hypoxia-induced and food restriction-induced growth retardation in the newborn rat. Moromisato, D.Y., Moromisato, M.Y., Brasel, J.A., Cooper, D.M. Crit. Care Med. (1999) [Pubmed]
  12. Growth restoration of insulin-deficient diabetic rats by recombinant human insulin-like growth factor I. Scheiwiller, E., Guler, H.P., Merryweather, J., Scandella, C., Maerki, W., Zapf, J., Froesch, E.R. Nature (1986) [Pubmed]
  13. Isolation of a cDNA clone encoding rat insulin-like growth factor-II precursor. Whitfield, H.J., Bruni, C.B., Frunzio, R., Terrell, J.E., Nissley, S.P., Rechler, M.M. Nature (1984) [Pubmed]
  14. Prolactin-stimulated production of somatomedin by rat liver. Francis, M.J., Hill, D.J. Nature (1975) [Pubmed]
  15. Growth hormone and the insulin-like growth factor system in myogenesis. Florini, J.R., Ewton, D.Z., Coolican, S.A. Endocr. Rev. (1996) [Pubmed]
  16. Growth hormone, the insulin-like growth factor system, and the kidney. Feld, S., Hirschberg, R. Endocr. Rev. (1996) [Pubmed]
  17. Expression of the IGF system in normal and diabetic transgenic (mRen-2)27 rat eye. Bergman, P.B., Moravski, C.J., Edmondson, S.R., Russo, V.C., Bach, L.A., Wilkinson-Berka, J.L., Werther, G.A. Invest. Ophthalmol. Vis. Sci. (2005) [Pubmed]
  18. Double-stranded ribonucleic acid decreases C6 rat glioma cell numbers: effects on insulin-like growth factor I gene expression and action. Chacko, M.S., Adamo, M.L. Endocrinology (2000) [Pubmed]
  19. Effects of continuous infusion of insulin-like growth factor I and II, alone and in combination with thyroxine or growth hormone, on the neonatal hypophysectomized rat. Glasscock, G.F., Hein, A.N., Miller, J.A., Hintz, R.L., Rosenfeld, R.G. Endocrinology (1992) [Pubmed]
  20. Protective effect of glutamine from glucocorticoid-induced muscle atrophy occurs without alterations in circulating insulin-like growth factor (IGF)-I and IGF-binding protein levels. Hickson, R.C., Oehler, D.T., Byerly, R.J., Unterman, T.G. Proc. Soc. Exp. Biol. Med. (1997) [Pubmed]
  21. Insulin-like Growth Factors and Their Binding Proteins Define Specific Phases of Myometrial Differentiation During Pregnancy in the Rat. Shynlova, O., Tsui, P., Dorogin, A., Langille, B.L., Lye, S.J. Biol. Reprod. (2007) [Pubmed]
  22. Insulin-like growth factor I gene expression in isolated rat renal collecting duct is stimulated by epidermal growth factor. Rogers, S.A., Miller, S.B., Hammerman, M.R. J. Clin. Invest. (1991) [Pubmed]
  23. Antiapoptotic signalling by the insulin-like growth factor I receptor, phosphatidylinositol 3-kinase, and Akt. Kulik, G., Klippel, A., Weber, M.J. Mol. Cell. Biol. (1997) [Pubmed]
  24. Platelet-derived growth factor isoforms decrease insulin-like growth factor I gene expression in rat vascular smooth muscle cells and selectively stimulate the biosynthesis of insulin-like growth factor binding protein 4. Giannella-Neto, D., Kamyar, A., Sharifi, B., Pirola, C.J., Kupfer, J., Rosenfeld, R.G., Forrester, J.S., Fagin, J.A. Circ. Res. (1992) [Pubmed]
  25. Thymic expression of insulin-related genes in an animal model of autoimmune type 1 diabetes. Kecha-Kamoun, O., Achour, I., Martens, H., Collette, J., Lefebvre, P.J., Greiner, D.L., Geenen, V. Diabetes Metab. Res. Rev. (2001) [Pubmed]
  26. Insulin-like growth factor binding proteins from cultured human fibroblasts. Characterization and hormonal regulation. Conover, C.A., Liu, F., Powell, D., Rosenfeld, R.G., Hintz, R.L. J. Clin. Invest. (1989) [Pubmed]
  27. Insulin-like growth factor I inhibits induction of nitric oxide synthase in vascular smooth muscle cells. Schini, V.B., Catovsky, S., Schray-Utz, B., Busse, R., Vanhoutte, P.M. Circ. Res. (1994) [Pubmed]
  28. Insulin-like growth factor I receptor signaling in differentiation of neuronal H19-7 cells. Morrione, A., Romano, G., Navarro, M., Reiss, K., Valentinis, B., Dews, M., Eves, E., Rosner, M.R., Baserga, R. Cancer Res. (2000) [Pubmed]
  29. Octreotide prevents the early increase in renal insulin-like growth factor binding protein 1 in streptozotocin diabetic rats. Raz, I., Rubinger, D., Popovtzer, M., Grønbaek, H., Weiss, O., Flyvbjerg, A. Diabetes (1998) [Pubmed]
  30. IGF-1 protects oligodendrocyte progenitors against TNFalpha-induced damage by activation of PI3K/Akt and interruption of the mitochondrial apoptotic pathway. Pang, Y., Zheng, B., Fan, L.W., Rhodes, P.G., Cai, Z. Glia (2007) [Pubmed]
  31. Corticosterone regulation of insulin-like growth factor I, IGF-binding proteins, and growth in streptozotocin-induced diabetic rats. Rodgers, B.D., Strack, A.M., Dallman, M.F., Hwa, L., Nicoll, C.S. Diabetes (1995) [Pubmed]
  32. Distinct sites of insulin-like growth factor (IGF)-II expression and localization in lesioned rat brain: possible roles of IGF binding proteins (IGFBPs) in the mediation of IGF-II activity. Walter, H.J., Berry, M., Hill, D.J., Cwyfan-Hughes, S., Holly, J.M., Logan, A. Endocrinology (1999) [Pubmed]
  33. Insulin-like growth factor-II (IGF-II), type 2 IGF receptor, and IGF-binding protein-2 gene expression in rat lung alveolar epithelial cells: relation to proliferation. Mouhieddine, O.B., Cazals, V., Maitre, B., Le Bouc, Y., Chadelat, K., Clement, A. Endocrinology (1994) [Pubmed]
  34. Expression, purification and characterization of the structure and disulfide linkages of insulin-like growth factor binding protein-4. Chelius, D., Baldwin, M.A., Lu, X., Spencer, E.M. J. Endocrinol. (2001) [Pubmed]
  35. Effect of insulin-like growth factor-1 and insulin-like growth factor binding protein-3 complex in cavernous nerve cryoablation. Bochinski, D., Hsieh, P.S., Nunes, L., Lin, G.T., Lin, C.S., Spencer, E.M., Lue, T.F. Int. J. Impot. Res. (2004) [Pubmed]
  36. IGF-I induced phosphorylation of S6K1 and 4E-BP1 in heart is impaired by acute alcohol intoxication. Lang, C.H., Kumar, V., Liu, X., Frost, R.A., Vary, T.C. Alcohol. Clin. Exp. Res. (2003) [Pubmed]
  37. Inhibition of phosphatidylinositol 3-kinase and p70S6 kinase blocks osteogenic protein-1 induction of alkaline phosphatase activity in fetal rat calvaria cells. Shoba, L.N., Lee, J.C. J. Cell. Biochem. (2003) [Pubmed]
  38. Insulin-stimulated oocyte maturation requires insulin receptor substrate 1 and interaction with the SH2 domains of phosphatidylinositol 3-kinase. Chuang, L.M., Myers, M.G., Backer, J.M., Shoelson, S.E., White, M.F., Birnbaum, M.J., Kahn, C.R. Mol. Cell. Biol. (1993) [Pubmed]
  39. Tumor necrosis factor-alpha and malnutrition-induced inhibition of diaphragm fiber growth in young rats. Lewis, M.I., Da, X., Li, H., Fournier, M. J. Appl. Physiol. (2005) [Pubmed]
  40. Glutamate excitotoxicity attenuates insulin-like growth factor-I prosurvival signaling. Garcia-Galloway, E., Arango, C., Pons, S., Torres-Aleman, I. Mol. Cell. Neurosci. (2003) [Pubmed]
  41. Insulin receptor substrate-1/SHP-2 interaction, a phenotype-dependent switching machinery of insulin-like growth factor-I signaling in vascular smooth muscle cells. Hayashi, K., Shibata, K., Morita, T., Iwasaki, K., Watanabe, M., Sobue, K. J. Biol. Chem. (2004) [Pubmed]
  42. Growth hormone action on proliferation and differentiation of cerebral cortical cells from fetal rat. Ajo, R., Cacicedo, L., Navarro, C., Sánchez-Franco, F. Endocrinology (2003) [Pubmed]
  43. Regulation of insulin-like growth factor-binding protein-5 expression during Schwann cell differentiation. Cheng, H.L., Shy, M., Feldman, E.L. Endocrinology (1999) [Pubmed]
  44. Expression and insulin-like growth factor-dependent proteolysis of insulin-like growth factor-binding protein-4 are regulated by cell confluence in vascular smooth muscle cells. Kamyar, A., Pirola, C.J., Wang, H.M., Sharifi, B., Mohan, S., Forrester, J.S., Fagin, J.A. Circ. Res. (1994) [Pubmed]
  45. Demonstration of receptors for insulin and insulin-like growth factors on Swarm rat chondrosarcoma chondrocytes. Evidence that insulin stimulates proteoglycan synthesis through the insulin receptor. Foley, T.P., Nissley, S.P., Stevens, R.L., King, G.L., Hascall, V.C., Humbel, R.E., Short, P.A., Rechler, M.M. J. Biol. Chem. (1982) [Pubmed]
  46. Promoter-dependent and -independent activation of insulin-like growth factor binding protein-5 gene expression by prostaglandin E2 in primary rat osteoblasts. McCarthy, T.L., Casinghino, S., Mittanck, D.W., Ji, C.H., Centrella, M., Rotwein, P. J. Biol. Chem. (1996) [Pubmed]
  47. Insulin-like growth factor I-mediated activation of the transcription factor cAMP response element-binding protein in PC12 cells. Involvement of p38 mitogen-activated protein kinase-mediated pathway. Pugazhenthi, S., Boras, T., O'Connor, D., Meintzer, M.K., Heidenreich, K.A., Reusch, J.E. J. Biol. Chem. (1999) [Pubmed]
  48. Specific amino acid substitutions determine the differential contribution of the N- and C-terminal domains of insulin-like growth factor (IGF)-binding protein-5 in binding IGF-I. Shand, J.H., Beattie, J., Song, H., Phillips, K., Kelly, S.M., Flint, D.J., Allan, G.J. J. Biol. Chem. (2003) [Pubmed]
  49. Expression of the genes encoding the rat renal insulin-like growth factor-I system. Rabkin, R., Brody, M., Lu, L.H., Chan, C., Shaheen, A.M., Gillett, N. J. Am. Soc. Nephrol. (1995) [Pubmed]
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