Insulin-like Growth Factor 2 (IGF-2)

Insulin-like growth factor II (IGF-II) is a 7.5 kilodalton, 67 amino acid peptide which is thought to mediate some of the actions of growth hormone (GH). IGF-II peptide consists of the A, C, and B chains, and is structurally homologous to IGF-I and proinsulin. IGF-II is secreted by the liver and other tissue and is postulated to have mitogenic and metabolic actions at or near the sites of synthesis; this has been termed the paracrine role of IGF-II. IGF-II also appears in the peripheral circulation, where it circulates primarily in a high molecular weight tertiary complex with IGF-binding protein-3 (IGFBP-3) and acid-labile subunit. A smaller proportion of IGF-II may circulate in association with other IGF-binding proteins. The proportion of unbound IGF-II in the circulation has been estimated at >5%. Plasma levels of IGF-II are dependent upon adequate levels of GH and other factors, including adequate nutrition.

The actions of IGF-II are mediated by binding to specific cell surface receptors. The function of the type II IGF receptor is not completely defined. IGF-II binds with lower affinity to the IGF-I type receptors and the insulin receptors. These latter receptors may mediate the mitogenic and metabolic actions of IGF-II. Although its specific physiologic role has not been defined, it has been postulated that the interplay of IGF-I and IGF-II with the different cell surface receptors and circulating binding proteins modulates tissue growth.

Normal postnatal plasma IGF-II levels are assumed to be at maximum levels, since administration of GH does not result in increased IGF-II levels (unlike IGF-I levels, which increase). Postnatal plasma IGF-II levels show a moderate age-related increase throughout childhood and puberty, and there is no significant variability during the day. IGF-II levels decrease in GH deficiency and in malnutrition. IGF-II levels may also decrease in acromegaly and during exogenous administration of IGF-I.