Strength Training Increases Insulin-Mediated Glucose Uptake, GLUT4 Content, and Insulin Signaling in Skeletal Muscle in Patients With Type 2 Diabetes

• Published in: Diabetes (New York, N.Y.) Vol. 53; no. 2; pp. 294 - 305
• Main Authors: Holten, Mads K., Zacho, Morten, Gaster, Michael, Juel, Carsten, Wojtaszewski, Jørgen F.P., Dela, Flemming
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Diabetes Association 01.02.2004
• Subjects: Biological and medical sciences; Biological Transport - drug effects; Capillaries - physiology; Capillaries - physiopathology; Case studies; Denmark; Diabetes Mellitus, Type 2 - physiopathology; Diabetes. Impaired glucose tolerance; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; European Continental Ancestry Group; Exercise; Exercise - physiology; Fundamental and applied biological sciences. Psychology; Glucose - metabolism; Glucose Transporter Type 4; Glycemic index; Glycogen - metabolism; Health aspects; Humans; Insulin; Insulin - pharmacology; Insulin - physiology; Leg; Male; Medical sciences; Monosaccharide Transport Proteins - metabolism; Muscle Fibers, Skeletal - drug effects; Muscle Fibers, Skeletal - physiology; Muscle Proteins; Muscle, Skeletal - drug effects; Muscle, Skeletal - physiology; Muscle, Skeletal - physiopathology; Physical Fitness; Reference Values; Striated muscle. Tendons; Tensile Strength - physiology; Type 2 diabetes; Vertebrates: osteoarticular system, musculoskeletal system; Denmark; United States; Type 2 diabetes; Endocrinopathy; Human; Signal transduction; Pancreatic hormone; Glucose; Striated muscle; Insulin; Uptake
• ISSN: 0012-1797; 1939-327X
• DOI: 10.2337/diabetes.53.2.294

Strength Training Increases Insulin-Mediated Glucose Uptake, GLUT4 Content, and Insulin Signaling in Skeletal Muscle in Patients With Type 2 Diabetes Mads K. Holten 1 2 , Morten Zacho 2 , Michael Gaster 3 , Carsten Juel 2 4 , Jørgen F.P. Wojtaszewski 2 5 and Flemming Dela 1 2 1 Department of Medical Physiology, the Panum Institute, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark 2 Copenhagen Muscle Research Centre, Rigshospitalet, Copenhagen, Denmark 3 Departments of Endocrinology and of Pathology, Odense University Hospital, Odense, Denmark 4 August Krogh Institute, Copenhagen, Denmark 5 Institute of Exercise and Sport Sciences, Faculty of Natural Sciences, University of Copenhagen, Copenhagen, Denmark Address correspondence and reprint requests to Flemming Dela, MD, Department of Medical Physiology, the Panum Institute, University of Copenhagen, Blegdamsvej 3, DK 2200 Copenhagen N, Denmark. E-mail: f.dela{at}mfi.ku.dk Abstract Strength training represents an alternative to endurance training for patients with type 2 diabetes. Little is known about the effect on insulin action and key proteins in skeletal muscle, and the necessary volume of strength training is unknown. A total of 10 type 2 diabetic subjects and 7 healthy men (control subjects) strength-trained one leg three times per week for 6 weeks while the other leg remained untrained. Each session lasted no more than 30 min. After strength training, muscle biopsies were obtained, and an isoglycemic-hyperinsulinemic clamp combined with arterio-femoral venous catheterization of both legs was carried out. In general, qualitatively similar responses were obtained in both groups. During the clamp, leg blood flow was higher ( P < 0.05) in trained versus untrained legs, but despite this, arterio-venous extraction glucose did not decrease in trained legs. Thus, leg glucose clearance was increased in trained legs ( P < 0.05) and more than explained by increases in muscle mass. Strength training increased protein content of GLUT4, insulin receptor, protein kinase B-α/β, glycogen synthase (GS), and GS total activity. In conclusion, we found that strength training for 30 min three times per week increases insulin action in skeletal muscle in both groups. The adaptation is attributable to local contraction-mediated mechanisms involving key proteins in the insulin signaling cascade. CS, citrate synthase FFA, free fatty acid G6P, glucose-6-phosphate GS, glycogen synthase HAD, hydroxyacyl-3-dehydrogenase HRP, horseradish peroxidase IRS-1, insulin receptor substrate-1 LDH, lactate dehydrogenase PI, phosphatidylinositol PKB, protein kinase B PMSF, phenylmethylsulfonyl fluoride PVDF, polyvinylidiene diflouride RM, repetition maximum Footnotes Accepted October 17, 2003. Received July 7, 2003. DIABETES