Short-Term Exercise Training Does Not Stimulate Skeletal Muscle ATP Synthesis in Relatives of Humans With Type 2 Diabetes

• Published in: Diabetes (New York, N.Y.) Vol. 58; no. 6; pp. 1333 - 1341
• Main Authors: Kacerovsky-Bielesz, Gertrud, Chmelik, Marek, Ling, Charlotte, Pokan, Rochus, Szendroedi, Julia, Farukuoye, Michaela, Kacerovsky, Michaela, Schmid, Albrecht I., Gruber, Stephan, Wolzt, Michael, Moser, Ewald, Pacini, Giovanni, Smekal, Gerhard, Groop, Leif, Roden, Michael
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Diabetes Association 01.06.2009
• Subjects: Adenosine Triphosphatases - genetics; Adenosine Triphosphatases - metabolism; Adenosine Triphosphate - biosynthesis; ATP synthesis; Biological and medical sciences; Care and treatment; Clinical Medicine; Diabetes; Diabetes mellitus; Diabetes Mellitus, Type 2 - genetics; Diabetes Mellitus, Type 2 - physiopathology; Diabetes. Impaired glucose tolerance; DNA Primers; Endocrine pancreas. Apud cells (diseases); Endocrinology and Diabetes; Endocrinopathies; Endokrinologi och diabetes; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Exercise; Family; Feeding Behavior; Fitness training programs; Fundamental and applied biological sciences. Psychology; Genes; Glucose; Glucose tolerance test; Glucose tolerance tests; Health aspects; Heat-Shock Proteins - genetics; Humans; Insulin resistance; Klinisk medicin; Lipids; Medical and Health Sciences; Medical sciences; Medicin och hälsovetenskap; Metabolism; Muscle, Skeletal - enzymology; Muscle, Skeletal - physiology; Muscles; NADH, NADPH Oxidoreductases - genetics; Original; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; Physical fitness; Polymorphism; Polymorphism, Genetic; Research design; Skeletal muscle; Spectrum analysis; Striated muscle. Tendons; Surveys and Questionnaires; Transcription Factors - genetics; Vertebrates: osteoarticular system, musculoskeletal system; Endocrinopathy; Short term; Type 2 diabetes; Physical exercise; Human; Metabolic diseases; Biosynthesis; Striated muscle; ATP
• ISSN: 0012-1797; 1939-327X; 1939-327X
• DOI: 10.2337/db08-1240

Short-Term Exercise Training Does Not Stimulate Skeletal Muscle ATP Synthesis in Relatives of Humans With Type 2 Diabetes Gertrud Kacerovsky-Bielesz 1 , 2 , Marek Chmelik 2 , 3 , Charlotte Ling 4 , Rochus Pokan 5 , Julia Szendroedi 1 , 2 , Michaela Farukuoye 2 , Michaela Kacerovsky 2 , Albrecht I. Schmid 2 , 3 , Stephan Gruber 3 , Michael Wolzt 6 , Ewald Moser 3 , Giovanni Pacini 7 , Gerhard Smekal 5 , Leif Groop 4 and Michael Roden 1 , 2 , 8 1 Medical Department, Hanusch Hospital, Vienna, Austria; 2 Karl-Landsteiner Institute for Endocrinology and Metabolism, Vienna, Austria; 3 MR Center of Excellence, Medical University of Vienna, Vienna, Austria; 4 Department of Clinical Sciences, Lund University, Malmö, Sweden; 5 Department of Sports and Exercise Physiology, University of Vienna, Vienna, Austria; 6 Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria; 7 Metabolic Unit, Institute of Biomedical Engineering, Consiglio Nazionale delle Ricerche, Padua, Italy; 8 Institute for Clinical Diabetology, German Diabetes Center-Leibniz Center for Diabetes Research, Department of Medicine/Metabolic Diseases, Heinrich Heine University Düsseldorf, Düsseldorf, Germany. Corresponding author: Michael Roden, michael.roden{at}ddz.uni-duesseldorf.de . Abstract OBJECTIVE We tested the hypothesis that short-term exercise training improves hereditary insulin resistance by stimulating ATP synthesis and investigated associations with gene polymorphisms. RESEARCH DESIGN AND METHODS We studied 24 nonobese first-degree relatives of type 2 diabetic patients and 12 control subjects at rest and 48 h after three bouts of exercise. In addition to measurements of oxygen uptake and insulin sensitivity (oral glucose tolerance test), ectopic lipids and mitochondrial ATP synthesis were assessed using 1 H and 31 P magnetic resonance spectroscopy, respectively. They were genotyped for polymorphisms in genes regulating mitochondrial function, PPARGC1A (rs8192678) and NDUFB6 (rs540467). RESULTS Relatives had slightly lower ( P = 0.012) insulin sensitivity than control subjects. In control subjects, ATP synthase flux rose by 18% ( P = 0.0001), being 23% higher ( P = 0.002) than that in relatives after exercise training. Relatives responding to exercise training with increased ATP synthesis (+19%, P = 0.009) showed improved insulin sensitivity ( P = 0.009) compared with those whose insulin sensitivity did not improve. A polymorphism in the NDUFB6 gene from respiratory chain complex I related to ATP synthesis ( P = 0.02) and insulin sensitivity response to exercise training ( P = 0.05). ATP synthase flux correlated with O 2 uptake and insulin sensitivity. CONCLUSIONS The ability of short-term exercise to stimulate ATP production distinguished individuals with improved insulin sensitivity from those whose insulin sensitivity did not improve. In addition, the NDUFB6 gene polymorphism appeared to modulate this adaptation. This finding suggests that genes involved in mitochondrial function contribute to the response of ATP synthesis to exercise training. Footnotes The funding bodies had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. Clinical trial reg. no. NCT00710008, clinicaltrials.gov. 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. Received September 6, 2008. Accepted February 27, 2009. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details. © 2009 by the American Diabetes Association.