Effects of insulin on cellular growth and proliferation

Insulin stimulates the growth and proliferation of a variety of cells in culture. The growth-stimulatory effects of insulin are observed in G_o/G_l arrested cells limited for serum growth factors or essential nutrients, and in cells growing in hormone-supplemented serum-free media. Some, but not all, of the effects of insulin on growth require superphysiological concentrations of insulin. The action of insulin on growth is synergistic with the action of other hormones and growth factors, including FGF, PDGF, PGF_2α and vasopressin. This observation, as well as other observations regarding the temporal sequence of action of growth factors, suggests that different growth factors act on different intracellular biochemical events. Several hypotheses have been proposed to explain the effect of insulin on cellular proliferation, including regulation of essential metabolic processes and interaction of insulin with receptors for insulin-like growth factors. Evidence supporting these various hypotheses is reviewed. In addition to the growth-stimulatory effect of insulin observed in cell culture, a number of clinical examples suggest that insulin is an important growth-regulating hormone during fetal development.