The long- and short-term effects of insulin on leucine turnover were investigated in six young healthy volunteers using [1-14C]leucine in combination with indirect calorimetry. After baseline measurement of leucine turnover (44.9 +/- 2.7 mumol.m-2.min-1), the plasma insulin concentration was raised by 10 microU/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 mumol.m-2.min-1, P < 0.001) and at 13 h (29.2 +/- 2.6 mumol.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 mumol.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 [14C]KIC or [14C]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.(ABSTRACT TRUNCATED AT 250 WORDS)