Impaired mitochondrial function and insulin resistance of skeletal muscle in mitochondrial diabetes

  1. Julia Szendroedi, MD, PhD1,2,
  2. Albrecht Ingo Schmid, PhD1,3,
  3. Martin Meyerspeer, PhD3,
  4. Camilla Cervin, PhD4,
  5. Michaela Kacerovsky, MD1,
  6. Gerhard Smekal, Prof MD5,
  7. Sabine Gräser-Lang, MD6,
  8. Leif Groop, Prof, MD, PhD4 and
  9. Michael Roden, Prof, MD (michael.roden{at}ddz.uni-duesseldorf.de)1,2
  1. 1First Medical Department and Karl-Landsteiner Institute for Endocrinology and Metabolism, Hanusch Hospital, Vienna, Austria
  2. 2Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center, and Department of Medicine/Metabolic Diseases, Heinrich-Heine University Düsseldorf, Germany
  3. 3MR Centre of Excellence, Med. Univ. Vienna, Austria
  4. 4Department of Clinical Sciences, Lund University, Sweden
  5. 5Institute of Sports Sciences, Department of Sport Physiology, University Vienna, Austria
  6. 6Neurological Outpatient Service, Hanusch Hospital, Vienna, Austria

    Abstract

    Objective: Impaired muscular mitochondrial function relates to common insulin resistance in type 2 diabetes. Mitochondrial diseases frequently lead to diabetes, which is mostly attributed to defective ß-cell mitochondria and secretion.

    Research Design and Methods: We assessed muscular mitochondrial function and lipid deposition in liver (HCL) and muscle (IMCL) using 31P/1H magnetic resonance spectroscopy (MRS), insulin sensitivity and endogenous glucose production (EGP) by hyperinsulinemic-euglycemic clamps combined with isotopic tracer dilution in one female suffering from the MELAS syndrome and in six controls (CON).

    Results: The patient showed impaired insulin sensitivity (4.3 vs. CON: 8.6±0.5 mg.kg−1.min−1) and suppression of EGP (69% vs. 94±1%). Baseline and insulin-stimulated ATP synthesis were reduced (7.3 and 8.9 μmol.l−1.min−1 vs. 10.6±1.0 and 12.8±1.3 μmol.l−1.min−1). HCL and IMCL were comparable with CON.

    Conclusions: Impairment of muscle mitochondrial fitness promotes insulin resistance and could thereby contribute to the development of diabetes in certain patients with the MELAS syndrome.

    Footnotes

      • Received November 18, 2008.
      • Accepted December 26, 2008.

    This Article

    1. Published online before print January 8, 2009, doi: 10.2337/dc08-2078
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