Insulin-Like Growth Factor 1

This chapter focuses on insulin-like growth factor 1 (IGF-1). The IGF-1 gene, located on chromosome band 12q22-q24, is approximately 100 kb long and contains six exons. Due to alternative transcription initiation, both ligands are produced from prenatal to postnatal periods. In fact, circulating IGF-2 levels in adults are higher than IGF-1 levels. IGF-1 is a pleiotropic growth factor with multiple roles in various aspects of normal and pathological growth and differentiation. The biological actions of IGF-1 are mediated by the IGF-1 receptor (IGFIR), a cell-surface heterotetramer structurally related to the insulin receptor. In addition, the effects of IGF-1 are modulated by a family of binding proteins (IGFBPs) that carry the ligand in the circulation and extracellular fluids. IGF-1 is widely expressed in the central nervous system (CNS), where it promotes proliferation, survival, and differentiation of neuronal and nonneuronal cells. Furthermore, IGF-1 is a potent neurotrophic factor, rescuing neurons from apoptosis and enhancing neuronal growth and myelination, and hence, understanding the role and regulation of the IGF-1 system will be of significant basic and clinical relevance.