Effects of insulin and amino acid infusion on leucine and phenylalanine kinetics in type 1 diabetes.

To evaluate the anabolic effects of hyperinsulinemia and hyperaminoacidemia on amino acid (and protein) metabolism in type 1 (insulin-dependent) diabetes mellitus (IDDM), we studied leucine and phenylalanine kinetics in nine IDDM and seven control subjects, both at basal euglycemic conditions and during a euglycemic hyperinsulinemic clamp (approximately 60-80 microU/ml of plasma free insulin), combined with an intravenous infusion of amino acids (AA), which doubled plasma concentrations of most AA. In the basal state, euglycemia was maintained in IDDM subjects at the expense of a peripheral free insulin level (16 +/- 2 microU/ml) greater (P less than 0.05) than controls (9 +/- 1 microU/ml). Despite that, leucine rate of appearance (Ra), alpha-ketoisocaproate oxidation (approximating leucine-carbon oxidation), and nonoxidative leucine disposal, were greater (P less than 0.05) in IDDM than in control subjects. Phenylalanine Ra was slightly but not significantly greater in IDDM vs. control subjects. During the clamp, at comparable plasma free insulin and amino acid concentrations, oxidation was similar in the two groups, endogenous leucine and phenylalanine Ra remained significantly greater (P less than 0.05) in IDDM than in normal subjects, and leucine disposal tended also to be greater in IDDM subjects. Thus, in IDDM subjects maintained at euglycemia, endogenous Ra of essential amino acid(s) (index of endogenous proteolysis) is increased, both in the postabsorptive state and after hyperinsulinemia combined with hyperaminoacidemia, while leucine utilization for protein synthesis is not impaired.