Insulin-like growth factor I, also known as somatomedin C, is the dominant effector of growth hormone and is structurally homologous to proinsulin. Human IGF-I is synthesized as two precursor isoforms with N- and alternate C-terminal propeptides (1). These isoforms are differentially expressed by various tissues (1). The 7.6 kDa mature IGF-I is identical between isoforms and is generated by proteolytic removal of the N- and C-terminal regions. Mature human IGF-I shares 94% and 96% aa sequence identity with mouse and rat IGF-I, respectively (2), and exhibits cross-species activity. It shares 64% aa sequence identity with mature human IGF-II. Circulating IGF-I is produced by hepatocytes, while local IGF-I is produced by many other tissues in which it has paracrine effects (1). IGF-I induces the proliferation, migration, and differentiation of a wide variety of cell types during development and postnatally (3). IGF-I regulates glucose and fatty acid metabolism, steroid hormone activity, and cartilage and bone metabolism (4 - 7). It plays an important role in muscle regeneration and tumor progression (1, 8). IGF-I binds IGF-I R, IGF-II R, and the insulin receptor, although its effects are mediated primarily by IGF-I R (9). IGF-I association with IGF binding proteins increases its plasma half-life and modulates its interactions with receptors (10).
1. Philippou, A. et al., 2007, In Vivo 21:45. 2. Sandberg-Nordqvist, A.C. et al., 1992, Brain Res. Mol. Brain Res. 12:275. 3. Guvakova, M.A., 2007, Int. J. Biochem. Cell Biol. 39:890. 4. Clemmons, D.R., 2006, Curr. Opin. Pharmacol. 6:620. 5. Bluher, S. et al., 2005, Best Pract. Res. Clin. Endocrinol. Metab. 19:577. 6. Garcia-Segura, L.M. et al., 2006, Neuroendocrinology 84:275. 7. Malemud, C.J., 2007, Clin. Chim. Acta 375:10. 8. Samani, A.A. et al., 2007, Endocrine Rev. 28:20. 9. LeRoith, D. and S. Yakar, 2007, Nat. Clin. Pract. Endocrinol. Metab. 3:302. 10. Denley, A. et al., 2005, Cytokine Growth Factor Rev. 16:421.