USE OF A LEUCINE CLAMP TO DEMONSTRATE THAT IGF-I ACTIVELY STIMULATES PROTEIN-SYNTHESIS IN NORMAL HUMANS

Insulin-like growth factor I (IGF-I) is thought to mediate the anabolic action of growth hormone. A glucose and amino acid clamp technique was used to investigate the effects of a 3-h intravenous infusion of either 43.7 pmol.kg(-1).min(-1) (20 mu g.kg(-1).h(-1)) IGF-I or 3.4 pmol.kg(-1).min(-1) (0.5 mU.kg(-1).min(-1)) insulin on whole body leucine turnover in five normal human volunteers. During the IGF-I infusion, IGF-I levels increased (P < 0.01; 26.6 +/- 2.8 to 88.9 +/- 14.2 nmol/l) and insulin levels fell (P < 0.05; 0.096 +/- 0.018 to 0.043 +/- 0.009 nmol/l). During the insulin infusion, insulin levels increased (P < 0.01; 0.057 +/- 0.013 to 0.340 +/- 0.099 nmol/l), and there was no change in IGF-I. There was no significant change in leucine production rate (R(a); a measure of protein degradation) during the IGF-I infusion (2.23 +/- 0.17 to 2.13 +/- 0.2 mu mol.kg(-1).min(-1)), but there was an increase (P < 0.03) in nonoxidative leucine disposal rate (R(d); a measure of protein synthesis; 1.83 +/- 0.15 to 2.05 +/- 0.21 mu mol.kg(-1).min(-1)). In contrast, insulin reduced (P < 0.02) leucine R(a) (1.81 +/- 0.24 to 1.47 +/- 0.24 mu mol.kg(-1).min(-1)) and had no effect on nonoxidative leucine R(d) (1.44 +/- 0.25 to 1.41 +/- 0.22 mu mol.kg(-1).min(-1)). We conclude that IGF-I, under conditions of adequate substrate supply, directly increases protein synthesis in contrast to insulin, which exerts its anabolic action by reducing proteolysis.