In many cell types, insulin-like growth factors (IGFs) have been shown to possess a variety of bioactivities, such as induction of growth or differentiation of target cells, cell survival and maintenance of cell function. On the other hand, insulin, whose structure is similar to IGFs, mediates anabolic biological activities, including increases in glucose and amino acids transport, induction of glycogen, lipid and protein syntheses, and inhibition of gluconeogenesis, lipolysis and protein degradation.
Despite the profuseness and diversity of these effects of IGFs, the in vitro biological effects of IGFs are relatively weak and often are not demonstrable except in the presence of other hormones or growth factors (Table 1). These findings suggest that IGFs act as permissive factors to augment the signals of other factors. This mechanism is very important in order that IGF induce specific bioactivities in the right tissues at the right times. Accordingly, to elucidate how IGF action is potentiated by other intercellular signaling molecules is essential for revealing IGF significance in target tissues.
In contrast, insulin resistance is an important inducer of diabetes mellitus. There are accumulated reports showing that various intercellular signaling molecules impair insulin signaling, leading to insulin resistance (Table 2). However, the precise mechanisms of action of each factor is not yet clear. Elucidation of each mechanism is very important for the development of specific treatments.
