COMPARISON OF THE EFFECTS OF RECOMBINANT HUMAN INSULIN-LIKE GROWTH FACTOR-I AND INSULIN ON GLUCOSE AND LEUCINE KINETICS IN HUMANS

To compare the metabolic effects of elevated plasma concentrations of IGF-I and insulin, overnight-fasted normal subjects were studied twice , once receiving IGF-I and once insulin at doses that resulted in iden tical increases in glucose uptake during 8-h euglycemic clamping. Reco mbinant human IGF-I or insulin were infused in one group at high doses (30 mug/kg per h IGF-I or 0.23 nmol/kg per h insulin) and in another group at low doses (5 mug/kg per h IGF-I or 0.04 nmol/kg per h insulin ). Glucose rate of disappearance (measured by 16,6-D2]-glucose infusio ns) increased from baseline by 239+/-16% during high dose IGF-I vs 197 +/-18% during insulin (P = 0.021 vs IGF-I). Hepatic glucose production decreased by 37+/-6% during high dose IGF-I vs 89+/-13% during insuli n (P = 0.0028 vs IGF-I). IGF-I suppressed whole body leucine flux ([1- C-13]-leucine infusion technique) more than insulin (42+/-4 vs 32+/-3% during high doses, P = 0.0082). Leucine oxidation rate decreased duri ng high dose IGF-I more than during insulin (55+/-4 vs 32+/-6%, P = 0. 0001 ). The decreases of plasma concentrations of free fatty acids, ac etoacetate, and beta-hydroxybutyrate after 8 h of IGF-I and insulin ad ministration were similar. Plasma C-peptide levels decreased by 57+/-4 % during high doses of IGF-I vs 36+/-6% during insulin (P 0.005 vs IGF -I). The present data demonstrate that, compared to insulin, an acute increase in plasma IGF-I levels results in preferential enhancement of peripheral glucose utilization, diminished suppression of hepatic glu cose production, augmented decrease of whole body protein breakdown (l eucine flux), and of irreversible leucine catabolism but in similar an tilipolytic effects. The data suggest that insulin-like effects of IGF -I in humans are mediated in part via IGF-I receptors and in part via insulin receptors.