Effects of Insulin and Amino Acids on Leg Protein Turnover in IDDM Patients

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leg tissue kinetics of [¹⁵N]phenylalanine and [1-¹³C]leucine and its metabolites were measured in eight insulin-withdrawn IDDM patients and eight nondiabetic subjects during basal insulinemia and during infusion of insulin (0.29 nmol · min⁻¹ [ m⁻²).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.