IGF-I alters skeletal muscle substrate metabolism and blunts recovery from insulin-induced hypoglycemia

Eight healthy subjects were treated with saline or insulin-like growth factor I (IGF-I, 10 mu g . kg(-1). h(-1) sc) for 3 days in a crossover randomized fashion. Substrate balances across the forearm skeletal vascular bed were determined in the postabsorptive state and during a hyperinsulinemic euglycemic clamp. In the basal state, net forearm uptake of free fatty acids and ketone bodies was increased during IGF-I administration in the face of elevated plasma levels of these substrates, whereas basal glucose levels and forearm glucose balance were unchanged. However, whole body and net forearm glucose uptakes were more markedly stimulated by insulin (+20 and +8%, respectively) in the IGF-I period. Additionally, counterregulatory hormone responses were examined during insulin-induced stepwise hypoglycemia. Responses of growth hormone and glucagon were blunted, those of cortisol and epinephrine were more marked, and that of norepineprine was unchanged during IGF-I administration. These changes were accompanied with delayed recovery from hypoglycemia.