We examined the effect of insulin and plasma amino acid concentrations on leucine kinetics in 15 healthy volunteers (age 22 ± 2 yrs) using the euglycemic insulin clamp technique and an infusion of [1-14C]leucine. Four different experimental conditions were examined: (a) study one, high insulin with reduced plasma amino acid concentrations; (b) study two, high insulin with maintenance of basal plasma amino acid concentrations; (c) study three, high insulin with elevated plasma amino acid concentrations; and (d) study four, basal insulin with elevated plasma amino acid concentrations. Data were analyzed using both the plasma leucine and alpha-ketoisocaproate (the alpha-ketoacid of leucine) specific activities. In study one total leucine flux, leucine oxidation, and nonoxidative leucine disposal (an index of whole body protein synthesis) all decreased (P < 0.01) regardless of the isotope model utilized. In study two leucine flux did not change, while leucine oxidation increased (P < 0.01) and nonoxidative leucine disposal was maintained at the basal rate; endogenous leucine flux (an index of whole body protein degradation) decreased (P < 0.01). In study three total leucine flux, leucine oxidation, and nonoxidative leucine disposal all increased (P < 0.001), while endogenous leucine flux decreased (P < 0.001). We conclude that: (a) hyperinsulinemia alone decreases plasma leucine concentration and inhibits endogenous leucine flux (protein breakdown), leucine oxidation, and nonoxidative leucine disposal (protein synthesis); (b) hyperaminoacidemia, whether in combination with hyperinsulinemia or with maintained basal insulin levels decreases endogenous leucine flux and stimulates both leucine oxidation and nonoxidative leucine disposal.
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