COMPARISON OF THE EFFECTS OF GROWTH-HORMONE AND INSULIN-LIKE GROWTH-FACTOR-I ON SUBSTRATE OXIDATION AND ON INSULIN SENSITIVITY IN GROWTH HORMONE-DEFICIENT HUMANS

Insulin-like growth factor-I (IGF-I) is considered to be the mediator of the growth-promoting effects of growth hormone (GH). The metabolic effects of these two hormones, however, are different. Whereas GH trea tment leads to elevated insulin and glucose levels, reduced insulin se nsitivity, and impaired glucose tolerance, IGF-I treatment leads to re duced insulin and GH levels and enhanced insulin sensitivity. IGF-I ma y, therefore, not only be the mediator of the growth-promoting effects of GH but also a modulator of the effects of GH on insulin action and glucose metabolism. To study the influence of GH and IGF-I on substra te metabolism and insulin sensitivity (assessed by euglycemic, hyperin sulinemic clamping combined with indirect calorimetry and glucose trac er infusion), we have treated eight GH-deficient adults with GH (2 IU/ m(2) daily subcutaneously [s.c.]), IGF-I (10 mu g/kg . h s.c.), or bot h hormones together for 7 d, respectively, and compared the effects of these treatment regimens with a control phase. Our findings suggest t hat (a) both GH and IGF-I promote lipolysis and lipid oxidation, albei t by different mechanisms; (b) treatment with either hormone is follow ed by enhanced energy expenditure and reduced protein oxidation; and ( c) IGF-I reverses the insulin resistance induced by GH.