Insulin as a growth factor

Abstract

Insulin is a potent mitogen for many cell types in vitro. During tissue culture, supraphysiological concentrations of insulin are necessary to promote cell replication in connective or musculoskeletal tissues. Insulin promotes the growth of these cells by binding, with low affinity, to the type I insulin-like growth factor (IGF) receptor, not through the high affinity insulin receptor. In other cell types, such as hepatocytes, embryonal carcinoma cells, or mammary tumor cells, the type I IGF receptor is virtually absent, and insulin stimulates the growth of these cells at physiological concentrations by binding to the high affinity insulin receptor. Both receptor systems activate phosphorylation reactions within the cell which extend to ribosomal proteins. Insulin acts synergistically with other factors, such as platelet-derived growth factor and epidermal growth factor, to stimulate the progression of cells through the cycle of proliferation. Abnormal insulin secretion or action, before or after birth, often is associated with disordered growth suggesting that insulin may function as a growth factor in vivo. Poor growth follows impaired insulin secretion in diabetes mellitus. This is associated with reduced circulating levels of IGF’s which may be partly responsible for the growth failure. Insulin has a direct action on release of IGF’s from the liver in vitro, but during experimental diabetes there is a reduced number of hepatic somatotropic receptors which could limit the ability of growth hormone to regulate IGF release. Diabetic children, treated conventionally, have normal circulating IGF levels, but both growth rate and serum IGF concentration may increase dramatically w hen diabetic control is optimized. Hyperinsulinaemia in the human fetus of a diabetic mother may result in somatic overgrowth as well as adiposity, whereas experimental fetal (animal) hyperinsulinaemia does not result in skeletal overgrowth, and promotes IGF release only at extreme levels. Conversely hypoinsulinemia, with or without nutritional deprivation, is associated with fetal growth retardation accompanied by low circulating IGF levels. It can be concluded that insulin functions as a growth factor in both normal and abnormal development. Insulin promotes the growth of selected tissues by a direct action; in others, such as the musculoskeletal system, the action is indirect via the regulation of IGF release. © 1985 International Pediatric Research Foundation, Inc.