TIME-DEPENDENT REGULATION BY INSULIN OF LEUCINE METABOLISM IN YOUNG HEALTHY-ADULTS

The long- and short-term effects of insulin on leucine turnover were investigated in six young healthy volunteers using [1-C-14]leucine in combination with indirect calorimetry. After baseline measurement of leucine turnover (44.9 +/- 2.7 mu mol.m(-2) min(-1)), the plasma insulin concentration was raised by 10 mu U/ml above baseline while maintaining euglycemia for 24 h. Repeat determinations of leucine turnover were carried out at 3 and 24 h. On a separate day, in three of the six subjects, leucine turnover also was quantitated after 13 h of equivalent hyperinsulinemia. Insulin significantly suppressed plasma leucine and ketoisocaproate (KIC) concentrations during short-term (3 h infusion, and this reduction persisted after 13 and 24 h of insulin administration. Endogenous leucine flux (an index of protein degradation) was decreased similarly by hyperinsulinemia at 3 h (34.2 +/- 2.9 mu mol.m(-2) min(-1), P < 0.001) and at 13 h (29.2 +/- 2.6 mu mol.m(-2) min(-1), P < 0.05 vs. baseline) but returned to the basal preinsulin rate after 24 h of insulinization (40.4 +/- 2.9 mu mol.m(-2) min(-1); P = not significant vs. baseline, P < 0.001 vs. 3 h, and P < 0.05 vs. 13-h studies). Leucine oxidation did not change significantly after either 3, 13, or 24 h of insulin infusion. Similar results were obtained whether the calculations were carried out using the [C-14]KIC or [C-14]leucine specific activities. Four separate subjects, treated in a similar manner to the experimental group, received a 24-h infusion of saline and thus served as the controls for time, nutritional status, and level of physical activity. In the control group all measures of leucine turnover were similar at baseline and after 24 h of saline infusion. Our results indicate that insulin exerts differential effects on plasma leucine concentration and leucine turnover as a function of time.