title: Effects of insulin and amino acids on leg protein turnover in IDDM patients.
abstract: 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leg tissue kinetics of [15N]phenylalanine and [1-13C]leucine and its metabolites were measured in eight insulin-withdrawn IDDM patients and eight nondiabetic subjects during basal insulinemia and during infusion of insulin (0.29 nmol.min-1.m-2).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 less than 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 less than 0.01). Insulin-stimulated glucose uptake in the diabetic patients (1.60 +/- 0.28 mumol.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.
authors.affiliation: Department of Anatomy and Physiology, University of Dundee, Scotland, UK.
authors.forename: W M
authors.initials: WM
authors.lastname: Bennet
authors.forename: A A
authors.initials: AA
authors.lastname: Connacher
authors.forename: R T
authors.initials: RT
authors.lastname: Jung
authors.forename: P
authors.initials: P
authors.lastname: Stehle
authors.forename: M J
authors.initials: MJ
authors.lastname: Rennie
mesh_terms: D000328:Adult; D000596:Amino Acids / Q000494:pharmacology*; D002247:Carbon Isotopes; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism*; D005260:Female; D006801:Humans; D007328:Insulin / Q000494:pharmacology*; D007700:Kinetics; D007930:Leucine / Q000378:metabolism; D008297:Male; D008433:Mathematics; D008954:Models, Biological; D009132:Muscles / Q000187:drug effects / Q000378:metabolism*; D009587:Nitrogen Isotopes; D010649:Phenylalanine / Q000378:metabolism; D011506:Proteins / Q000378:metabolism*; D012016:Reference Values
chemical_list: D000596:Amino Acids; D002247:Carbon Isotopes; D007328:Insulin; D009587:Nitrogen Isotopes; D011506:Proteins; D010649:Phenylalanine; D007930:Leucine