ROLE OF THE INSULIN-LIKE GROWTH-FACTORS IN THE ENDOCRINE CONTROL OF GLUCOSE-HOMEOSTASIS

There is a growing body of evidence that the insulin-like growth facto rs (IGF-I and IGF-II) are dynamically involved in the regulation of gl ucose homeostasis, with one of their binding proteins, IGFBP-1, playin g a counterregulatory role. The IGFs are structurally and functionally related to insulin and in the circulation they represent a huge hypog lycemic potential which is buffered by their association with the IGFB Ps. The predominant IGFBP in serum, IGFBP-3, is able to form a high mo lecular weight complex with the IGFs and this complex is retained in t he circulation and appears to act as a reservoir of IGFs. The IGFs and IGFBP-3 are regulated in the long term by changes in nutritional stat us. In contrast, IGFBP-1 is acutely regulated in a manner similar to g lucose counterregulatory hormones. IGFBP-1 is able to block the insuli n-like actions of the circulating IGFs and when administered alone as a bolus infusion causes an increase in blood glucose levels. There is recent evidence that more IGFs are available for an endocrine glucoreg ulatory role than indicated by estimates of steady-state 'free' IGF le vels. The IGF/IGFBP system may thus play a complementary role to insul in and the classical counterregulatory hormones in the control of bloo d glucose.