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

  1. Gertrud Kacerovsky-Bielesz1,2,
  2. Marek Chmelik2,3,
  3. Charlotte Ling4,
  4. Rochus Pokan5,
  5. Julia Szendroedi1,2,
  6. Michaela Farukuoye2,
  7. Michaela Kacerovsky2,
  8. Albrecht I. Schmid2,3,
  9. Stephan Gruber3,
  10. Michael Wolzt6,
  11. Ewald Moser3,
  12. Giovanni Pacini7,
  13. Gerhard Smekal5,
  14. Leif Groop4 and
  15. Michael Roden1,2,8
  1. 1Medical Department, Hanusch Hospital, Vienna, Austria;
  2. 2Karl-Landsteiner Institute for Endocrinology and Metabolism, Vienna, Austria;
  3. 3MR Center of Excellence, Medical University of Vienna, Vienna, Austria;
  4. 4Department of Clinical Sciences, Lund University, Malmö, Sweden;
  5. 5Department of Sports and Exercise Physiology, University of Vienna, Vienna, Austria;
  6. 6Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria;
  7. 7Metabolic Unit, Institute of Biomedical Engineering, Consiglio Nazionale delle Ricerche, Padua, Italy;
  8. 8Institute for Clinical Diabetology, German Diabetes Center-Leibniz Center for Diabetes Research, Department of Medicine/Metabolic Diseases, Heinrich Heine University Düsseldorf, Düsseldorf, Germany.
  1. 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 using1H and31P 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 O2uptake 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.

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  1. Diabetes vol. 58 no. 6 1333-1341
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