Responses of whole body glucose disposal (GDR) and protein breakdown (PB) to physiological insulin levels are altered in nondiabetic elderly subjects. Amino acids enhance inhibition of PB by insulin in young subjects. We hypothesized that addition of amino acid to insulin may improve the defect in PB regulation by insulin in elderly people. Therefore, we investigated the effect of hyperinsulinemia combined to either euaminoacidemia (EuAA) or hyperaminoacidemia (HyperAA) on GDR and PB, using isotopic dilution of D-[6,6-2H2]glucose and L-[1-13C]leucine, in young (mean +/- SEM, 24.4 +/- 0.8 yr) and elderly (70.2 +/- 0.7 yr) subjects. GDR was lower in elderly than in young subjects in all situations (P < 0.05). Despite a greater inhibition with HyperAA, PB was less inhibited in elderly than in young subjects during both clamps (ratio between change over basal PB and change over basal insulinemia, -0.014 +/- 0.002 vs. -0.024 +/- 0.003 in EuAA and -0.022 +/- 0.002 vs. -0.036 +/- 0.003 micromol/ml.microU/kg fat-free mass.min in HyperAA; elderly vs. young, P < 0.05). In conclusion, in nondiabetic elderly subjects, PB is less inhibited by insulin with either basal or high amino acid concentrations. Addition of amino acid potentiates insulin-induced suppression of PB in both groups to the same extent, suggesting a specific dysregulation of PB by insulin with age.