Synthesis Rate of Muscle Proteins, Muscle Functions, and Amino Acid Kinetics in Type 2 Diabetes

• Published in: Diabetes (New York, N.Y.) Vol. 51; no. 8; pp. 2395 - 2404
• Main Authors: HALVATSIOTIS, Panagiotis, SHORT, Kevin R, BIGELOW, Maureen, SREEKUMARAN NAIR, K
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Diabetes Association 01.08.2002
• Subjects: Abnormalities; Amino Acids - metabolism; Biological and medical sciences; Blood Glucose - metabolism; Carbon Isotopes; Diabetes Mellitus, Type 2 - drug therapy; Diabetes Mellitus, Type 2 - metabolism; Diabetes Mellitus, Type 2 - physiopathology; Diabetes. Impaired glucose tolerance; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Energy Intake; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Glucose metabolism; Humans; Hypoglycemic Agents - therapeutic use; Insulin - blood; Insulin - therapeutic use; Kinetics; Leucine - metabolism; Medical sciences; Middle Aged; Muscle Fatigue; Muscle proteins; Muscle Proteins - biosynthesis; Muscle, Skeletal - metabolism; Muscle, Skeletal - physiopathology; Phenylalanine - metabolism; Physiological aspects; Reference Values; Type 1 diabetes; Type 2 diabetes; Greece; United States; Endocrinopathy; Human; Protein synthesis; Aminoacid; Kinetics; Striated muscle; Non insulin dependent diabetes; Protein
• ISSN: 0012-1797; 1939-327X
• DOI: 10.2337/diabetes.51.8.2395

Synthesis Rate of Muscle Proteins, Muscle Functions, and Amino Acid Kinetics in Type 2 Diabetes Panagiotis Halvatsiotis , Kevin R. Short , Maureen Bigelow and K. Sreekumaran Nair From the Division of Endocrinology, Mayo Clinic and Foundation, Rochester, Minnesota 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 V o 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. Footnotes Address correspondence and reprint requests to K. Sreekumaran Nair, MD, Mayo Foundation, 200 1st St. SW, Rm 5-194 Joseph, Rochester, MN 55905. E-mail: nair.sree{at}mayo.edu . Received for publication 25 October 2001 and accepted in revised form 15 May 2002. P.H. is currently affiliated with the Hellenic National Diabetes Center, Athens, Greece. AIR g , acute insulin response to glucose; FFM, fat-free mass; FSR, fractional synthetic rate; GCRC, General Clinical Research Center; HPLC, high-performance liquid chromatography; IRMA, immunoradiometric assay; S I , insulin sensitivity; T 2 D+, intensive insulin treatment group; T 2 D−, treatment withdrawn group. DIABETES