Nutritional Regulation of Hepatic Production of IGF-1

Abstract

Insulin-like Growth Factor-1 (IGF-1) is a low molecular weight peptide (7.5 kDa), structurally related to proinsulin, that stimulates growth and exhibits insulin-like metabolic effects. In contrast with most hormonal peptides, IGF-1 is secreted as it is produced. Consequently, there are no organs where IGF-1 is concentrated. Although the liver is believed to be the principal source of circulating IGF-1, the highest concentrations are observed in blood. IGF-1 is produced in most organs and exerts biological effects on most cell types. The ubiquity of sites of production and action has led to the concept that this peptide acts by autocrine and paracrine mechanisms, as well as by classical endocrine mechanisms. IGF-1 mediates most of the anabolic actions of growth hormone (GH) and, therefore, is considered to be an important postnatal growth factor (1). IGF-1 stimulates growth in GH-deficient rats and GH-insensitive humans and reverses the catabolic effects of caloric restriction in normal volunteers (2). IGF-1 can mimick most of the growth-promoting effects of GH. Besides its anabolic properties, IGF-1 exerts multiple insulin-like metabolic effects. Its infusion decreases blood glucose and inhibits lipolysis and protein breakdown (3). IGF-1, however, seems less potent than insulin in decreasing glycemia. IGF-1 in serum and most of body fluids is complexed with high affinity-binding proteins (IGFBPs). Seven distinct IGF binding proteins have been characterized (IGFBP-1 to 7), and most of them are present in serum (4).