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Gene Review

Igf1  -  insulin-like growth factor 1

Mus musculus

Synonyms: C730016P09Rik, IGF-I, Igf-1, Igf-I, Insulin-like growth factor I, ...
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Disease relevance of Igf1


Psychiatry related information on Igf1

  • Disturbed cross talk between insulin-like growth factor I and AMP-activated protein kinase as a possible cause of vascular dysfunction in the amyloid precursor protein/presenilin 2 mouse model of Alzheimer's disease [5].
  • The insulin-like growth factor I (IGF-1)/Akt pathway plays a crucial role in Huntington's disease by phosphorylating the causative protein, polyQ-huntingtin, and abolishing its toxic properties [Humbert et al. (2002)Dev. Cell, 2, 831-837; Rangone et al. (2004)Eur. J. Neurosci., 19, 273-279] [6].
  • At 20 mo of age, the LI-IGF-I-/- mice displayed a more prominent decrease in activity level with decreased horizontal activity throughout the test period, and at day 1, there were several signs of an altered habituation process with different time patterns of locomotor activity and horizontal activity compared with the control mice [7].
  • Neuroprotective effects of IGF-I against TNFalpha-induced neuronal damage in HIV-associated dementia [8].
  • Mice lacking IGF-I lose many auditory neurons and present increased auditory thresholds at early postnatal ages [9].

High impact information on Igf1


Chemical compound and disease context of Igf1


Biological context of Igf1

  • However, the appearance of E2-induced mitotic figures and cell number increases were profoundly retarded in Igf1-null uterine tissue [18].
  • To test these hypotheses, we compared E2's mitogenic effects on the uteri of Igf1-targeted gene deletion (null) and wild-type littermate mice [18].
  • The proportion of uterine cells involved in the cell cycle and G1- and S-phase kinetics were not significantly different in wild-type and Igf1-null mice [18].
  • The terminal hypertrophic chondrocytes, which form the scaffold on which long bone growth extends, are reduced in linear dimension by 30% in Igf1 null mice, accounting for most of their decreased longitudinal growth [1].
  • Combined ablation of Igf1 and Igf2, the ligands for these two receptors, resulted in an identical phenotype [19].

Anatomical context of Igf1


Associations of Igf1 with chemical compounds

  • The expression of the insulin-sensitive glucose transporter, GLUT4, is significantly decreased and the insulin-regulated enzyme glycogen synthase kinase 3beta (GSK3) is hypo-phosphorylated in Igf1 null chondrocytes [1].
  • The myelin-associated lipids galactocerebroside and sulfatide were modestly reduced in Igf1(-/-) brains [20].
  • Heterozygous Igf1 mutant mice [I(+/-) II(wt)] were crossed with heterozygous Igf1 mutant, phosphoenolpyruvate carboxykinase promoter IGF-II transgenic mice [I(+/-) II(tg)], and [I(+/+) II(wt)], [I(+/+) II(tg)], [I(-/-) II(wt)], and [I(-/-) II(tg)] offspring were investigated [21].
  • Investigation of factors critically involved in dendritic growth and synaptogenesis showed an approximately 50% reduction in cortical CDC42 protein expression (P <.001) and an approximately 10% reduction in brain cholesterol levels (P <.01) in Igf1 null mice [22].
  • Oocyte glycogen stores, determined by PAS staining, did not appear different in Igf1-/- and wt mice.GLUT3 was expressed in thecal cells surrounding growing follicles and was not appreciably different in Igf1 null compared with wt ovaries [23].
  • Hence, in contrast to the general opinion that the trophic activity of IGF-1 is solely mediated by tyrosine kinase receptor-associated signalling, we show that it involves a more complex signalling network dependent on the PAC1 Gs-protein-coupled receptor in neurons [24].
  • NBI-31772 binds all six IGFBPs with high affinity and releases "free" endogenous IGF-I [25].
  • IGF-I receptor (IGF-IR) and IGF-I signaling were blocked by preadministration of NVP-AEW541 and through the use of IGF-I knockout mice, respectively [26].

Physical interactions of Igf1


Enzymatic interactions of Igf1

  • The residual insulin/IGF-1 action correlated with the appearance of a new tyrosine-phosphorylated protein (IRS-2) which binds to PI(3)K, but is slightly larger than and immunologically distinct from IRS-1 [32].
  • The Crk proto-oncogene product is an SH2 and SH3 domain-containing adaptor protein which we have previously shown to become rapidly tyrosine phosphorylated in response to stimulation with insulin-like growth factor I (IGF-I) in NIH-3T3 cells [33].
  • Src phosphorylates the insulin-like growth factor type I receptor on the autophosphorylation sites. Requirement for transformation by src [34].
  • These findings have functional significance since alpha(2)M protects IGFBP-1 from proteolysis and abrogates the inhibitory effect of phosphorylated IGFBP-1 on IGF-I stimulated 3T3-L1 cell proliferation [35].

Regulatory relationships of Igf1


Other interactions of Igf1


Analytical, diagnostic and therapeutic context of Igf1


  1. Igf1 promotes longitudinal bone growth by insulin-like actions augmenting chondrocyte hypertrophy. Wang, J., Zhou, J., Bondy, C.A. FASEB J. (1999) [Pubmed]
  2. Effects of Igf1 gene deletion on postnatal growth patterns. Wang, J., Zhou, J., Powell-Braxton, L., Bondy, C. Endocrinology (1999) [Pubmed]
  3. Simian virus 40 large tumor antigen is unable to transform mouse embryonic fibroblasts lacking type 1 insulin-like growth factor receptor. Sell, C., Rubini, M., Rubin, R., Liu, J.P., Efstratiadis, A., Baserga, R. Proc. Natl. Acad. Sci. U.S.A. (1993) [Pubmed]
  4. Insulin-like growth factor I is a dual effector of multiple myeloma cell growth. Ge, N.L., Rudikoff, S. Blood (2000) [Pubmed]
  5. Disturbed cross talk between insulin-like growth factor I and AMP-activated protein kinase as a possible cause of vascular dysfunction in the amyloid precursor protein/presenilin 2 mouse model of Alzheimer's disease. Lopez-Lopez, C., Dietrich, M.O., Metzger, F., Loetscher, H., Torres-Aleman, I. J. Neurosci. (2007) [Pubmed]
  6. Akt is altered in an animal model of Huntington's disease and in patients. Colin, E., Régulier, E., Perrin, V., Dürr, A., Brice, A., Aebischer, P., Déglon, N., Humbert, S., Saudou, F. Eur. J. Neurosci. (2005) [Pubmed]
  7. Liver-derived IGF-I regulates exploratory activity in old mice. Svensson, J., Söderpalm, B., Sjögren, K., Engel, J., Ohlsson, C. Am. J. Physiol. Endocrinol. Metab. (2005) [Pubmed]
  8. Neuroprotective effects of IGF-I against TNFalpha-induced neuronal damage in HIV-associated dementia. Ying Wang, J., Peruzzi, F., Lassak, A., Del Valle, L., Radhakrishnan, S., Rappaport, J., Khalili, K., Amini, S., Reiss, K. Virology (2003) [Pubmed]
  9. Trophic effects of insulin-like growth factor-I (IGF-I) in the inner ear. Varela-Nieto, I., Morales-Garcia, J.A., Vigil, P., Diaz-Casares, A., Gorospe, I., Sánchez-Galiano, S., Cañon, S., Camarero, G., Contreras, J., Cediel, R., Leon, Y. Hear. Res. (2004) [Pubmed]
  10. beta-cell-specific deletion of the Igf1 receptor leads to hyperinsulinemia and glucose intolerance but does not alter beta-cell mass. Kulkarni, R.N., Holzenberger, M., Shih, D.Q., Ozcan, U., Stoffel, M., Magnuson, M.A., Kahn, C.R. Nat. Genet. (2002) [Pubmed]
  11. Localized Igf-1 transgene expression sustains hypertrophy and regeneration in senescent skeletal muscle. Musarò, A., McCullagh, K., Paul, A., Houghton, L., Dobrowolny, G., Molinaro, M., Barton, E.R., Sweeney, H.L., Rosenthal, N. Nat. Genet. (2001) [Pubmed]
  12. Irs-2 coordinates Igf-1 receptor-mediated beta-cell development and peripheral insulin signalling. Withers, D.J., Burks, D.J., Towery, H.H., Altamuro, S.L., Flint, C.L., White, M.F. Nat. Genet. (1999) [Pubmed]
  13. Castration-induced apoptosis of androgen-dependent shionogi carcinoma is associated with increased expression of genes encoding insulin-like growth factor-binding proteins. Nickerson, T., Miyake, H., Gleave, M.E., Pollak, M. Cancer Res. (1999) [Pubmed]
  14. Enhancement of insulin-like growth factor signaling in human breast cancer: estrogen regulation of insulin receptor substrate-1 expression in vitro and in vivo. Lee, A.V., Jackson, J.G., Gooch, J.L., Hilsenbeck, S.G., Coronado-Heinsohn, E., Osborne, C.K., Yee, D. Mol. Endocrinol. (1999) [Pubmed]
  15. Increased expression of platelet-derived growth factor A and insulin-like growth factor-I in BAL cells during the development of bleomycin-induced pulmonary fibrosis in mice. Maeda, A., Hiyama, K., Yamakido, H., Ishioka, S., Yamakido, M. Chest (1996) [Pubmed]
  16. Insulin-like growth factor I receptors on mouse neuroblastoma cells. Two beta subunits are derived from differences in glycosylation. Ota, A., Wilson, G.L., Leroith, D. Eur. J. Biochem. (1988) [Pubmed]
  17. Insulin-like growth factor I gene expression is induced in astrocytes during experimental demyelination. Komoly, S., Hudson, L.D., Webster, H.D., Bondy, C.A. Proc. Natl. Acad. Sci. U.S.A. (1992) [Pubmed]
  18. Insulin-like growth factor 1 is required for G2 progression in the estradiol-induced mitotic cycle. Adesanya, O.O., Zhou, J., Samathanam, C., Powell-Braxton, L., Bondy, C.A. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
  19. Effects of mutations in the insulin-like growth factor signaling system on embryonic pancreas development and beta-cell compensation to insulin resistance. Kido, Y., Nakae, J., Hribal, M.L., Xuan, S., Efstratiadis, A., Accili, D. J. Biol. Chem. (2002) [Pubmed]
  20. Biochemical and morphometric analyses show that myelination in the insulin-like growth factor 1 null brain is proportionate to its neuronal composition. Cheng, C.M., Joncas, G., Reinhardt, R.R., Farrer, R., Quarles, R., Janssen, J., McDonald, M.P., Crawley, J.N., Powell-Braxton, L., Bondy, C.A. J. Neurosci. (1998) [Pubmed]
  21. Postnatally Elevated Levels of Insulin-Like Growth Factor (IGF)-II Fail to Rescue the Dwarfism of IGF-I-Deficient Mice except Kidney Weight. Moerth, C., Schneider, M.R., Renner-Mueller, I., Blutke, A., Elmlinger, M.W., Erben, R.G., Camacho-H??bner, C., Hoeflich, A., Wolf, E. Endocrinology (2007) [Pubmed]
  22. Insulin-like growth factor 1 is essential for normal dendritic growth. Cheng, C.M., Mervis, R.F., Niu, S.L., Salem, N., Witters, L.A., Tseng, V., Reinhardt, R., Bondy, C.A. J. Neurosci. Res. (2003) [Pubmed]
  23. Reduced GLUT1 expression in Igf1-/- null oocytes and follicles. Zhou, J., Bievre, M., Bondy, C.A. Growth Horm. IGF Res. (2000) [Pubmed]
  24. PACAP type I receptor transactivation is essential for IGF-1 receptor signalling and antiapoptotic activity in neurons. Delcourt, N., Thouvenot, E., Chanrion, B., Galéotti, N., Jouin, P., Bockaert, J., Marin, P. EMBO J. (2007) [Pubmed]
  25. Modulation of insulin-like growth factor (IGF)-I and IGF-binding protein interactions enhances skeletal muscle regeneration and ameliorates the dystrophic pathology in mdx mice. Schertzer, J.D., Gehrig, S.M., Ryall, J.G., Lynch, G.S. Am. J. Pathol. (2007) [Pubmed]
  26. Glucagon-like peptide-2 activates beta-catenin signaling in the mouse intestinal crypt: role of insulin-like growth factor-I. Dubé, P.E., Rowland, K.J., Brubaker, P.L. Endocrinology (2008) [Pubmed]
  27. An insulin-like growth factor (IGF) binding protein enhances the biologic response to IGF-I. Elgin, R.G., Busby, W.H., Clemmons, D.R. Proc. Natl. Acad. Sci. U.S.A. (1987) [Pubmed]
  28. Structural determinants for high-affinity binding of insulin-like growth factor II to insulin receptor (IR)-A, the exon 11 minus isoform of the IR. Denley, A., Bonython, E.R., Booker, G.W., Cosgrove, L.J., Forbes, B.E., Ward, C.W., Wallace, J.C. Mol. Endocrinol. (2004) [Pubmed]
  29. Gene expression of the insulin-like growth factor system during mouse kidney development. Lindenbergh-Kortleve, D.J., Rosato, R.R., van Neck, J.W., Nauta, J., van Kleffens, M., Groffen, C., Zwarthoff, E.C., Drop, S.L. Mol. Cell. Endocrinol. (1997) [Pubmed]
  30. Responses of insulin-like growth factor (IGF)-I and IGF-binding proteins to nutritional status in peroxisome proliferator-activated receptor-alpha knockout mice. Lewitt, M.S., Brismar, K., Wang, J., Wivall-Helleryd, I.L., Sindelar, P., Gonzalez, F.J., Bergman, T., Bobek, G.A. Growth Horm. IGF Res. (2001) [Pubmed]
  31. Insulin-like growth factor (IGF)-I/IGF-binding protein-3 complex: therapeutic efficacy and mechanism of protection against type 1 diabetes. Chen, W., Salojin, K.V., Mi, Q.S., Grattan, M., Meagher, T.C., Zucker, P., Delovitch, T.L. Endocrinology (2004) [Pubmed]
  32. Alternative pathway of insulin signalling in mice with targeted disruption of the IRS-1 gene. Araki, E., Lipes, M.A., Patti, M.E., Brüning, J.C., Haag, B., Johnson, R.S., Kahn, C.R. Nature (1994) [Pubmed]
  33. The proto-oncogene product c-Crk associates with insulin receptor substrate-1 and 4PS. Modulation by insulin growth factor-I (IGF) and enhanced IGF-I signaling. Beitner-Johnson, D., Blakesley, V.A., Shen-Orr, Z., Jimenez, M., Stannard, B., Wang, L.M., Pierce, J., LeRoith, D. J. Biol. Chem. (1996) [Pubmed]
  34. Src phosphorylates the insulin-like growth factor type I receptor on the autophosphorylation sites. Requirement for transformation by src. Peterson, J.E., Kulik, G., Jelinek, T., Reuter, C.W., Shannon, J.A., Weber, M.J. J. Biol. Chem. (1996) [Pubmed]
  35. alpha 2-Macroglobulin: a new component in the insulin-like growth factor/insulin-like growth factor binding protein-1 axis. Westwood, M., Aplin, J.D., Collinge, I.A., Gill, A., White, A., Gibson, J.M. J. Biol. Chem. (2001) [Pubmed]
  36. Differential roles of the insulin and insulin-like growth factor-I (IGF-I) receptors in response to insulin and IGF-I. Entingh-Pearsall, A., Kahn, C.R. J. Biol. Chem. (2004) [Pubmed]
  37. Nuclear translocation of insulin receptor substrate-1 by oncogenes and Igf-I. Effect on ribosomal RNA synthesis. Tu, X., Batta, P., Innocent, N., Prisco, M., Casaburi, I., Belletti, B., Baserga, R. J. Biol. Chem. (2002) [Pubmed]
  38. Protein kinase C negatively regulates Akt activity and modifies UVC-induced apoptosis in mouse keratinocytes. Li, L., Sampat, K., Hu, N., Zakari, J., Yuspa, S.H. J. Biol. Chem. (2006) [Pubmed]
  39. Smoking Induces Glomerulosclerosis in Aging Estrogen-Deficient Mice through Cross-Talk between TGF-beta1 and IGF-I Signaling Pathways. Elliot, S.J., Karl, M., Berho, M., Xia, X., Pereria-Simon, S., Espinosa-Heidmann, D., Striker, G.E. J. Am. Soc. Nephrol. (2006) [Pubmed]
  40. Preimplantation embryo development in vitro: cooperative interactions among embryos and role of growth factors. Paria, B.C., Dey, S.K. Proc. Natl. Acad. Sci. U.S.A. (1990) [Pubmed]
  41. Involvement of transforming growth factor beta1 in autocrine enhancement of gelatinase B secretion by murine metastatic colon carcinoma cells. Shimizu, S., Nishikawa, Y., Kuroda, K., Takagi, S., Kozaki, K., Hyuga, S., Saga, S., Matsuyama, M. Cancer Res. (1996) [Pubmed]
  42. Protein kinase B/AKT 1 plays a pivotal role in insulin-like growth factor-1 receptor signaling induced 3T3-L1 adipocyte differentiation. Xu, J., Liao, K. J. Biol. Chem. (2004) [Pubmed]
  43. Growth hormone-releasing hormone antagonist MZ-5-156 inhibits growth of DU-145 human androgen-independent prostate carcinoma in nude mice and suppresses the levels and mRNA expression of insulin-like growth factor II in tumors. Lamharzi, N., Schally, A.V., Koppán, M., Groot, K. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  44. The insulin-like growth factor axis and prostate cancer: lessons from the transgenic adenocarcinoma of mouse prostate (TRAMP) model. Kaplan, P.J., Mohan, S., Cohen, P., Foster, B.A., Greenberg, N.M. Cancer Res. (1999) [Pubmed]
  45. Tumor necrosis factor alpha inhibits transcriptional activity of the porcine P-45011A insulin-like growth factor response element. Urban, R.J., Nagamani, M., Bodenburg, Y. J. Biol. Chem. (1996) [Pubmed]
  46. Impact of androgens, growth hormone, and igf-I on bone and muscle in male mice during puberty. Venken, K., Mov??rare-Skrtic, S., Kopchick, J.J., Coschigano, K.T., Ohlsson, C., Boonen, S., Bouillon, R., Vanderschueren, D. J. Bone Miner. Res. (2007) [Pubmed]
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