The effects of infusion of insulinlike growth factor (IGF) I, IGF-II, and insulin on glucose and protein metabolism in fasted lambs

Abstract

In vivo effects of 300-min infusions of recombinant insulinlike growth factor I (IGF-I) and IGF-II on glucose and protein metabolism have been investigated in awake, fasted lambs. Two doses of recombinant human (rh) IGF-I were infused: 6.7 nmol/ kg · h, which induced hypoglycemia, and 2.0 nmol/kg · h, which did not. The effects were compared with an insulin infusion (0.17 nmol/kg · h) that had the same hypoglycemic potential as the high dose rhIGF-I infusion. rhIGF-II was infused at a rate of 6.7 nmol/kg · h. Primed constant infusions of isotopically labeled glucose, urea and leucine tracers were used to determine glucose and protein kinetics. rhIGF-I lowered blood glucose by increasing the rate of glucose clearance (P < 0.01), in contrast to insulin, which both increased clearance and reduced glucose production. Net protein loss was reduced after infusion of low and high dose rhIGF-I and insulin by 11% (P < 0.05), 15% (P < 0.01), and 12% (P < 0.05), respectively. rhIGF-II infusion did not alter the rate of net protein loss. In contrast to insulin, high dose rhIGF-I infusion increased the rate of protein synthesis in skeletal (P < 0.05) and cardiac muscle (P < 0.01) and in hepatic tissue (P < 0.05). We conclude that (a) protein metabolism is more sensitive than glucose metabolism to rhIGF-I infusion, as protein loss was reduced by an rhIGF-I infusion that did not alter glucose kinetics; (b) protein synthesis is increased by rhIGF-I infusion but not by insulin infusion; and (c) rhIGF-II is a less effective anabolic agent than rhIGF-I. We speculate that the effects of rhIGF-I on protein metabolism are not mediated by insulin receptors.