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Gene Review

IGF1  -  insulin-like growth factor 1 (somatomedin C)

Homo sapiens

Synonyms: IBP1, IGF-I, IGF1A, IGFI, Insulin-like growth factor I, ...
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Disease relevance of IGF1


Psychiatry related information on IGF1


High impact information on IGF1


Chemical compound and disease context of IGF1


Biological context of IGF1

  • Both aminoacid substitutions were located close to tyrosine phosphorylation motifs that are putative recognition sites for insulin and IGF1 signal transmission proteins [21].
  • Moreover, hIGF-1R-infected cells will be useful in investigating the mechanisms of IGF1-mediated signal transduction because they are now known to proliferate in response to IGF-1 [22].
  • These findings suggest that up-regulation of glucose transporter and IGF1 expression may contribute to estrogen's salutary effects on neural tissue [23].
  • H358 cells secrete a high level of amphiregulin that, in combination with IGF1, prevents serum deprivation apoptosis [3].
  • The insulin-like growth factors, IGF1 and IGF2, play a fundamental role in human fetal growth [24].

Anatomical context of IGF1

  • Long-term survival of most RGCs in culture can be promoted by a combination of trophic factors normally produced along the visual pathway, including BDNF, CNTF, IGF1, an oligodendrocyte-derived protein, and forskolin [25].
  • In this study we have exploited the high affinity and specificity of IGF-binding protein 4 (IGF-BP4) and IGF-BP5 for IGF1 and IGF2 to determine whether these growth factors are involved in the nerve sprouting reaction in paralyzed skeletal muscle [26].
  • In tissue culture experiments with sensory- and motoneurons we demonstrate that the neurite promoting activity of IGF1 is blocked by IGF-BP4, and that a similar IGF-BP-sensitive activity is detected in muscle extracts from paralyzed, but not from control muscle [26].
  • Activation of ribosomal protein S6 kinase by epidermal growth factor (EGF), insulin, and insulin-like growth factor 1 (IGF1) was studied in the human mammary tumor cell line ZR-75-1 in isotonic buffers [27].
  • The chimeric proteins bound to the IGF1 receptors of the human lymphoblast IM-9, albeit with reduced affinity, and elicited some of the same biologic effects (increased glucose and amino acid uptake) in human KB cells as did human IGF1, but with reduced specific activity [28].

Associations of IGF1 with chemical compounds

  • Insulin, at 400 ng/ml only, increased HR by 36 +/- 10%, an effect simulated by lower concentrations of insulin-like growth factor-1 (IGF1) [29].
  • In contrast to the responses to EGF, insulin- and IGF1-activation of S6 kinase was enhanced when glucose was present and depended on the presence of bicarbonate in the medium [27].
  • This study provides novel data showing that Gluts 3 and 4 and IGF1 are coexpressed by primate cerebral cortical neurons, where their expression is enhanced by estrogen [23].
  • In addition, phosphorylation of PKCdelta and PKCzeta/lambda, but not of PKCalpha/beta(II), increases in serum-starved H358 cells and in H322 cells treated with an AR/IGF1 combination and is blocked by calphostin C [30].
  • The molecule with IGF1 attached after CH3 (CH3-IGF1) had reduced ability to carry out complement-mediated cytolysis [31].
  • The addition of these alphaVbeta3 ligands to SMCs grown in 5 mM glucose was sufficient to permit IGF-I-stimulated Shc phosphorylation and downstream signaling [32].
  • Whether the differences in the IGF-I response to GH between these children reflect differences in the respective anabolic (growth promotion) and metabolic (i.e. insulin action modulation) roles of circulating IGF-I is unknown [33].
  • Common genetic variation in IGF1 alters IGF-1 concentrations but is not associated with growth, glucose metabolism or type 1 diabetes [34].

Physical interactions of IGF1

  • In contrast, iodinated IGF-2 bound to a receptor where IGF-1 and IGF-2 were equipotent [35].
  • These data suggest that the positive charges in the C- and D-regions of IGF-1 contribute significantly to the binding preference of the IGF-1R for IGF-1 [36].
  • We show here that tIGF-I, a non-IGFBP-binding analogue of IGF-1, is a more potent mitogenic stimulator of the keratinocyte cell line HaCaT than IGF-I, suggesting that keratinocytes produce IGFBPs that modulate their response to IGF-I [37].
  • In this report, we demonstrate that IGF-1/insulin induced production of keratinocyte-derived autocrine growth factors that bind to the EGF receptor [38].
  • In the fetal circulation IGFBP-1 and IGFBP-2 appear to be the major binding proteins for IGF-1 [39].

Regulatory relationships of IGF1


Other interactions of IGF1

  • We used an IGF-1 analogue (des(1-3)IGF-I) with a > 100-fold reduction in affinity for IGFBP-1 as well as an IGFBP-1 mutant (WGD-IGFBP-1) which does not associate with the alpha5beta1 integrin to selectively abrogate each of these interactions [45].
  • Around midgestation a separate IGF-1 receptor, indicated by the preferential displacement of iodinated IGF-1 by IGF-1, appeared [35].
  • The signal for IGF-IA mRNA induction seems to be initiated via the monocyte AGE-receptor, and to be propagated in an autocrine fashion via either IL-1 beta or PDGF [46].
  • Insulin/IGF-1 cannot activate EGF receptor tyrosine kinase that has been inhibited by mAb 225 [47].
  • Messenger RNAs for IGF-1, IGF-2, and IGFBP-4 were detected by Northern analysis [48].
  • BRCA1 silencing by siRNA was used to investigate the effect of BRCA mutations on IGF-I protein expression [49].

Analytical, diagnostic and therapeutic context of IGF1

  • However, some animal studies and clinical trials have questioned whether elevating IGF1 chronically is beneficial [50].
  • Monoclonal antibodies to insulin-like growth factors 1 and 2 (IGF1 and IGF2) were used to investigate their distribution in diabetic foot ulcers and surrounding tissues by immunohistochemistry, compared with diabetic and non-diabetic uninjured skin [4].
  • 50 to 80% of the patients respond to daily multiple subcutaneous injections with insulin-like growth factor-1 (IGF1) levels being normalised in about 40 to 50% of them [51].
  • Conversely, IGF1 and IGF2 overexpression potently increased cellular proliferation rates and the efficiency of tumor formation in mouse xenograft experiments, whereas the resistance to chemotherapeutic drugs such as taxol was unaltered [52].
  • Polymerase chain reaction (PCR) and direct sequencing failed to demonstrate an alteration in the region upstream the IGF1 start site in Pygmies [53].


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  19. Substrate specificities of the insulin and insulin-like growth factor 1 receptor tyrosine kinase catalytic domains. Xu, B., Bird, V.G., Miller, W.T. J. Biol. Chem. (1995) [Pubmed]
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  21. Aminoacid polymorphisms of insulin receptor substrate-1 in non-insulin-dependent diabetes mellitus. Almind, K., Bjørbaek, C., Vestergaard, H., Hansen, T., Echwald, S., Pedersen, O. Lancet (1993) [Pubmed]
  22. Growth-promoting effects of insulin-like growth factor-1 (IGF-1) on hematopoietic cells: overexpression of introduced IGF-1 receptor abrogates interleukin-3 dependency of murine factor-dependent cells by a ligand-dependent mechanism. McCubrey, J.A., Steelman, L.S., Mayo, M.W., Algate, P.A., Dellow, R.A., Kaleko, M. Blood (1991) [Pubmed]
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  26. Role of muscle insulin-like growth factors in nerve sprouting: suppression of terminal sprouting in paralyzed muscle by IGF-binding protein 4. Caroni, P., Schneider, C., Kiefer, M.C., Zapf, J. J. Cell Biol. (1994) [Pubmed]
  27. Role of extracellular electrolytes in the activation of ribosomal protein S6 kinase by epidermal growth factor, insulin-like growth factor 1, and insulin in ZR-75-1 cells. Novak-Hofer, I., Küng, W., Eppenberger, U. J. Cell Biol. (1988) [Pubmed]
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  44. Interaction of scaffolding adaptor protein Gab1 with tyrosine phosphatase SHP2 negatively regulates IGF-I-dependent myogenic differentiation via the ERK1/2 signaling pathway. Koyama, T., Nakaoka, Y., Fujio, Y., Hirota, H., Nishida, K., Sugiyama, S., Okamoto, K., Yamauchi-Takihara, K., Yoshimura, M., Mochizuki, S., Hori, M., Hirano, T., Mochizuki, N. J. Biol. Chem. (2008) [Pubmed]
  45. Interaction between the insulin-like growth factor family and the integrin receptor family in tissue repair processes. Evidence in a rabbit ear dermal ulcer model. Galiano, R.D., Zhao, L.L., Clemmons, D.R., Roth, S.I., Lin, X., Mustoe, T.A. J. Clin. Invest. (1996) [Pubmed]
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  48. Insulinlike growth factor-binding protein modulates the growth response to insulinlike growth factor 1 by human gastric cancer cells. Guo, Y.S., Beauchamp, R.D., Jin, G.F., Townsend, C.M., Thompson, J.C. Gastroenterology (1993) [Pubmed]
  49. Intratumoral IGF-I protein expression is selectively upregulated in breast cancer patients with BRCA1/2 mutations. Hudelist, G., Wagner, T., Rosner, M., Fink-Retter, A., Gschwantler-Kaulich, D., Czerwenka, K., Kroiss, R., Tea, M., Pischinger, K., Köstler, W.J., Attems, J., Mueller, R., Blaukopf, C., Kubista, E., Hengstschläger, M., Singer, C.F. Endocr. Relat. Cancer (2007) [Pubmed]
  50. The insulin-like growth factor 1 receptor induces physiological heart growth via the phosphoinositide 3-kinase(p110alpha) pathway. McMullen, J.R., Shioi, T., Huang, W.Y., Zhang, L., Tarnavski, O., Bisping, E., Schinke, M., Kong, S., Sherwood, M.C., Brown, J., Riggi, L., Kang, P.M., Izumo, S. J. Biol. Chem. (2004) [Pubmed]
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