INTERACTION BETWEEN IGF-I, INSULIN AND GROWTH-HORMONE IN TYPE-II DIABETES

Insulin-like growth factor I (IGF-I) has been shown to enhance insulin sensitivity in type II diabetes and to improve glycemic control. Howe ver, the mechanism by which IGF-I alters insulin sensitivity is not we ll defined. The purpose of these studies was to determine whether grow th hormone (GH) would alter the effect of IGF-I on glucose homeostasis . The effect of two weeks of IGF-I administration on insulin and gluco se concentrations that were measured during a typical modal day was de fined for nine patients with type II diabetes, Subsequently, the effec t of a single injection of GH on the capacity ofIGF-I to suppress insu lin and to reduce glucose was also determined, The changes in IGF bind ing proteins 2 and 3 and the amount of IGF-I that bound to each form o f IGFBP was also determined in the subjects before and after IGF-I and following GH administration. GH was shown to partially antagonize the effects of IGF-I on glucose and insulin levels. GH had minimal effect s on total IGFBP-2 and IGFBP-3 but markedly altered the amount of IGF- I that was associated with each form of IGFBP. The distribution of IGF -I binding to IGFBP 2 and 3 in the patients treated with IGF-I alone w as significantly different compared to the patients treated with GH pl us IGF-I. Specifically, a much greater percentage of the IGF-I was ass ociated with IGFBP-2 in the patients that were treated with IGF-I alon e. This pool of IGF-I is known to equilibrate more rapidly with IGF-I in the extravascular space. These findings suggest that GH may functio n to alter the glycemic response to insulin by altering IGF-I bioavail ability and that its effects may be mediated in part through alteratio ns in the distribution of IGFs among the various forms of IGFBPs leadi ng to an alteration in IGF-I actions.