Insulin Through the Ages: Phylogeny of a Growth Promoting and Metabolic Regulatory Hormone1

Abstract

Insulin was discovered in 1922 as the causative factor for a human metabolic disorder (diabetes mellitus), but it was recognized early that the hormone had a broad phylogenetic distribution. By the mid 1970s, insulin had been isolated and sequenced from all classes of vertebrates, including Agnatha. Also it was discovered that the insulin gene family in vertebrates included two closely related hormones named insulin-like growth factor (IGF)-I and -II. More recently, the application of recombinant DNA techniques have identified insulin-like peptide genes in invertebrates, including insects, molluscs and nematode and these findings clearly establish that insulin is an evolutionarily ancient hormone which is present in all metazoa. Here we briefly review the structure and function of the insulin/IGF gene family in vertebrates and invertebrates. Although these studies are ongoing, it appears that in invertebrates the insulin-like peptides function predominately as mitogenic growth factors that act to promote tissue growth and development. However, in vertebrates the mitogenic growth function has been subsumed by IGF-I and -II while insulin has acquired the function of being primarily a metabolic regulatory hormone. The gene duplication and divergence events necessary for this development probably occurred early during vertebrate evolution in the transition from protochordates, represented by extant amphioxus, to primitive jawless vertebrates, represented by extant lamprey and hagfish.