title: Synthesis rate of muscle proteins, muscle functions, and amino acid kinetics in type 2 diabetes.
abstract: Improvement of glycemic status by insulin is associated with profound changes in amino acid metabolism in type 1 diabetes. In contrast, a dissociation of insulin effect on glucose and amino acid metabolism has been reported in type 2 diabetes. Type 2 diabetic patients are reported to have reduced muscle oxidative enzymes and VO(2max). We investigated the effect of 11 days of intensive insulin treatment (T(2)D+) on whole-body amino acid kinetics, muscle protein synthesis rates, and muscle functions in eight type 2 diabetic subjects after withdrawing all treatments for 2 weeks (T(2)D-) and compared the results with those of weight-matched lean control subjects using stable isotopes of the amino acids. Whole-body leucine, phenylalanine and tyrosine fluxes, leucine oxidation, and plasma amino acid levels were similar in all groups, although plasma glucose levels were significantly higher in T(2)D-. Insulin treatment reduced leucine nitrogen flux and transamination rates in subjects with type 2 diabetes. Synthesis rates of muscle mitochondrial, sarcoplasmic, and mixed muscle proteins were not affected by glycemic status or insulin treatment in subjects with type 2 diabetes. Muscle strength was also unaffected by diabetes or glycemic status. In contrast, the diabetic patients showed increased tendency for muscle fatigability. Insulin treatment also failed to stimulate muscle cytochrome C oxidase activity in the diabetic patients, although it modestly elevated citrate synthase. In conclusion, improvement of glycemic status by insulin treatment did not alter whole-body amino acid turnover in type 2 diabetic subjects, but leucine nitrogen flux, transamination rates, and plasma ketoisocaproate level were decreased. Insulin treatments in subjects with type 2 diabetes had no effect on muscle mitochondrial protein synthesis and cytochrome C oxidase, a key enzyme for ATP production.
authors.affiliation: Division of Endocrinology, Mayo Clinic and Foundation, Rochester, Minnesota 55905, USA.
authors.forename: Panagiotis
authors.initials: P
authors.lastname: Halvatsiotis
authors.forename: Kevin R
authors.initials: KR
authors.lastname: Short
authors.forename: Maureen
authors.initials: M
authors.lastname: Bigelow
authors.forename: K Sreekumaran
authors.initials: KS
authors.lastname: Nair
mesh_terms: D000596:Amino Acids / Q000378:metabolism*; D001786:Blood Glucose / Q000378:metabolism; D002247:Carbon Isotopes; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology*; D002149:Energy Intake; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007328:Insulin / Q000097:blood / Q000627:therapeutic use*; D007700:Kinetics; D007930:Leucine / Q000378:metabolism; D008875:Middle Aged; D018763:Muscle Fatigue; D009124:Muscle Proteins / Q000096:biosynthesis*; D018482:Muscle, Skeletal / Q000378:metabolism / Q000503:physiopathology*; D010649:Phenylalanine / Q000378:metabolism; D012016:Reference Values
chemical_list: D000596:Amino Acids; D001786:Blood Glucose; D002247:Carbon Isotopes; D007004:Hypoglycemic Agents; D007328:Insulin; D009124:Muscle Proteins; D010649:Phenylalanine; D007930:Leucine