Mitochondrial Respiration Is Decreased in Skeletal Muscle of Patients With Type 2 Diabetes

• Published in: Diabetes (New York, N.Y.) Vol. 56; no. 6; pp. 1592 - 1599
• Main Authors: Mogensen, Martin, Sahlin, Kent, Fernström, Maria, Glintborg, Dorte, Vind, Birgitte F., Beck-Nielsen, Henning, Højlund, Kurt
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Diabetes Association 01.06.2007
• Subjects: 3-Hydroxyacyl CoA Dehydrogenases - metabolism; Biological and medical sciences; Biopsy; Blood Glucose - metabolism; Cell respiration; Citrate (si)-Synthase - metabolism; Dehydrogenases; Diabetes; Diabetes Mellitus, Type 2 - metabolism; Diabetes Mellitus, Type 2 - pathology; Diabetes. Impaired glucose tolerance; Electron Transport; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Fundamental and applied biological sciences. Psychology; Glucose; Humans; Insulin resistance; Lipids; Male; Medical sciences; Medicin/Teknik; Medicine/Technology; Metabolism; Middle Aged; Mitochondria; Mitochondria, Muscle - metabolism; Mitochondria, Muscle - pathology; Mitochondrial DNA; Muscle, Skeletal - metabolism; Musculoskeletal system; Obesity; Obesity - metabolism; Obesity - pathology; Oxidation; Oxidative stress; Oxygen Consumption; Phosphorylation; Physiological aspects; Protons; Reference Values; Respiration; Striated muscle. Tendons; Type 2 diabetes; Vertebrates: osteoarticular system, musculoskeletal system; Denmark; Endocrinopathy; Type 2 diabetes; Human; Mitochondria; Metabolic diseases; Striated muscle; Respiration
• ISSN: 0012-1797; 1939-327X; 1939-327X
• DOI: 10.2337/db06-0981

Mitochondrial Respiration Is Decreased in Skeletal Muscle of Patients With Type 2 Diabetes Martin Mogensen 1 , Kent Sahlin 1 2 3 , Maria Fernström 2 3 , Dorte Glintborg 4 , Birgitte F. Vind 4 , Henning Beck-Nielsen 4 and Kurt Højlund 4 1 Institute of Sports Science and Clinical Biomechanics, University of Southern Denmark, Odense, Denmark 2 Stockholm University College of Physical Education and Sports, GIH, Stockholm, Sweden 3 Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden 4 Department of Endocrinology, Diabetes Research Centre, Odense University Hospital, Odense, Denmark Address correspondence and reprint requests to Kurt Højlund, MD, PhD, Diabetes Research Centre, Department of Endocrinology, Odense University Hospital, Kloevervaenget 6, 3, DK-5000 Odense C, Denmark. E-mail: k.hojlund{at}dadlnet.dk Abstract We tested the hypothesis of a lower respiratory capacity per mitochondrion in skeletal muscle of type 2 diabetic patients compared with obese subjects. Muscle biopsies obtained from 10 obese type 2 diabetic and 8 obese nondiabetic male subjects were used for assessment of 3-hydroxy-Acyl-CoA-dehydrogenase (HAD) and citrate synthase activity, uncoupling protein (UCP)3 content, oxidative stress measured as 4-hydroxy-2-nonenal (HNE), fiber type distribution, and respiration in isolated mitochondria. Respiration was normalized to citrate synthase activity (mitochondrial content) in isolated mitochondria. Maximal ADP-stimulated respiration (state 3) with pyruvate plus malate and respiration through the electron transport chain (ETC) were reduced in type 2 diabetic patients, and the proportion of type 2X fibers were higher in type 2 diabetic patients compared with obese subjects (all P < 0.05). There were no differences in respiration with palmitoyl- l -carnitine plus malate, citrate synthase activity, HAD activity, UCP3 content, or oxidative stress measured as HNE between the groups. In the whole group, state 3 respiration with pyruvate plus malate and respiration through ETC were negatively associated with A1C, and the proportion of type 2X fibers correlated with markers of insulin resistance ( P < 0.05). In conclusion, we provide evidence for a functional impairment in mitochondrial respiration and increased amount of type 2X fibers in muscle of type 2 diabetic patients. These alterations may contribute to the development of type 2 diabetes in humans with obesity. ETC, electron transport chain FFA, free fatty acid HAD, 3-hydroxy-Acyl-CoA-dehydrogenase HNE, 4-hydroxy-2-nonenal HOMA-IR, homeostasis model assessment of insulin resistance RCI, respiratory control index ROS, reactive oxygen species UCP, uncoupling protein Footnotes Published ahead of print at http://diabetes.diabetesjournals.org on 9 March 2007. DOI: 10.2337/db06-0981. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. Accepted February 26, 2007. Received July 17, 2006. DIABETES