ISLET AMYLOID POLYPEPTIDE DECREASES THE EFFECTS OF INSULIN-LIKE GROWTH-FACTOR-I ON GLUCOSE-TRANSPORT AND GLYCOGEN-SYNTHESIS IN SKELETAL-MUSCLE

Previous studies have shown that islet amyloid polypeptide (IAPP) is c o-secreted with insulin from the p-cell. IAPP reduces insulin-stimulat ed rates of glycogen synthesis in skeletal muscle but the mechanisms a re unclear. Insulin-like growth factor I (IGF-I) is an important regul ator of glucose metabolism in skeletal muscle and acts through its own receptor, which has many structural and functional similarities with the insulin receptor. Despite this, the effects of IGF-I on glucose ut ilization are not identical to those of insulin. The aim of the study was to determine the effects of IAPP on IGF-I-stimulated rates of gluc ose transport and metabolism (measured by 3-O-methyl[H-3]glucose and [ U-C-14]glucose, respectively) in rat soleus muscle, and compare them w ith those stimulated by insulin. IAPP (10 nM) decreased the sensitivit y of 3-O-methylglucose transport, the flux of glucose to hexosemonopho sphate and the sensitivity of glycogen synthesis to IGF-I. In contrast , IAPP had no effect on IGF-I-stimulated rates of lactate formation (i .e. glycolysis). IAPP decreased the sensitivity of 3-O-methylglucose t ransport and glycogen synthesis to insulin. It is concluded that IAPP blunts the stimulation of glucose uptake and deposition by IGF-I or in sulin in skeletal muscle. These observations expand those made initial ly for IAPP and insulin and suggest that IAPP affects IGF-I- or insuli n-stimulated glucose metabolism in muscle by a mechanism which is comm on for both hormones. These experiments may serve as a framework for f uture studies in order to clarify the mechanisms by which IAPP affects glucose metabolism in skeletal muscle. (C) 1998 Published by Elsevier Science Ltd. All rights reserved.