To determine whether the responses of muscle protein metabolism to insulin and amino acids in patients with insulin-dependent diabetes mellitus (IDDM) were different from those in nondiabetic subjects, leg tissue kinetics of [15N]phenylalanine and [1-13C]leucine and its metabolites were measured in eight insulin-withdrawn IDDM patients and eight nondiabetic subjects during basal insulinemia and during infusion of insulin (0.29 nmol · min−1 [ m−2). The diabetic patients were studied in the absence of amino acids, and both groups were studied during infusion of a mixed–amino acid solution (AA). In the diabetic patients, insulin alone and combined with additional AA reduced leg tissue phenylalanine release by 42 and 41%, respectively (both P < 0.05), but uptake was unchanged. Leg tissue leucine oxidation was unchanged by insulin alone but was increased (P = 0.012) fourfold during insulin infusion with additional AA. In the nondiabetic subjects, insulin with AA infusion increased leg tissue phenylalanine uptake (45.7 ± 7.5 to 73.1 ± 7.3 nmol · min−1 · 100 g−1, P < 0.01). Insulin-stimulated glucose uptake in the diabetic patients (1.60 ± 0.28 μmol · min−1 · 100 g−1,was impaired compared with the nondiabetic subjects (3.37 ± 0.28 μmol min −1 100 g−1, P = 0.04). These results suggest that, in IDDM patients, 1) infusion of insulin fails to stimulate muscle protein synthesis even when combined with a substantially increased provision of AA, and 2) compared with nondiabetic subjects, muscle protein synthesis as well as glucose uptake exhibit blunted responses to insulin.

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