Insulin and related growth factors: effects on the nervous system and mechanism for neurite growth and regeneration.

The neurobiological, behavioral and electrical effects of insulin and insulinlike growth factors (IGFs) are reviewed. Emphasis is placed on the emerging evidence that insulin and IGFs are members of a supergene family whose encoded polypeptides are functionally related not only as growth factors but also as neuroactive agents. The neurophysiology of insulin and its homologs is more fully illuminated through comparison against the classic neurotrophic agent, nerve growth factor (NGF). The IGFs and NGF are strongly implicated as having important roles in nerve regeneration, based on an examination of their neurotrophic properties and pattern of gene expression following nerve injury. The elucidation of the molecular mechanism by which neuritogenic polypeptides modulate neurite growth may eventually contribute to our understanding of the architectural development of neural circuitries on which higher animal behavior rests, and also provide the basis for new therapeutic approaches to nervous system injuries and disorders. The recent studies showing that these neuritogenic polypeptides may share a common mechanism involving elevation of tubulin transcripts, due at least in part to stabilization, are discussed. A substantial body of evidence now implicates phosphorylation as the receptor-mediated transmembrane event triggered by the neuritogenic polypeptides.