Impaired Mitochondrial Function and Insulin Resistance of Skeletal Muscle in Mitochondrial Diabetes
- Julia Szendroedi, MD, PHD1,2,
- Albrecht Ingo Schmid, PHD1,3,
- Martin Meyerspeer, PHD3,
- Camilla Cervin, PHD4,
- Michaela Kacerovsky, MD1,
- Gerhard Smekal, MD5,
- Sabine Gräser-Lang, MD6,
- Leif Groop, MD, PHD4 and
- Michael Roden, MD1,2
- 1First Medical Department and Karl-Landsteiner Institute for Endocrinology and Metabolism, Hanusch Hospital, Vienna, Austria;
- 2Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center, Department of Medicine/Metabolic Diseases, Heinrich-Heine University Düsseldorf, Düsseldorf, Germany;
- 3MR Centre of Excellence, Medical University of Vienna, Vienna, Austria;
- 4Department of Clinical Sciences, Lund University, Lund, Sweden;
- 5Department of Sport Physiology, Institute of Sports Sciences, University of Vienna, Vienna, Austria;
- 6Neurological Outpatient Service, Hanusch Hospital, Vienna, Austria.
- Corresponding author: Michael Roden, michael.roden{at}ddz.uni-duesseldorf.de.
Abstract
OBJECTIVE Impaired muscular mitochondrial function is related to common insulin resistance in type 2 diabetes. Mitochondrial diseases frequently lead to diabetes, which is mostly attributed to defective β-cell mitochondria and secretion.
RESEARCH DESIGN AND METHODS We assessed muscular mitochondrial function and lipid deposition in liver (hepatocellular lipids [HCLs]) and muscle (intramyocellular lipids [IMCLs]) using 31P/1H magnetic resonance spectroscopy and insulin sensitivity and endogenous glucose production (EGP) using hyperinsulinemic-euglycemic clamps combined with isotopic tracer dilution in one female patient suffering from MELAS (myopathy, encephalopathy, lactic acidosis, and stroke-like episodes) syndrome and in six control subjects.
RESULTS The MELAS patient showed impaired insulin sensitivity (4.3 vs. 8.6 ± 0.5 mg · kg−1 · min−1) and suppression of EGP (69 vs. 94 ± 1%), and her baseline and insulin-stimulated ATP synthesis were reduced (7.3 and 8.9 vs. 10.6 ± 1.0 and 12.8 ± 1.3 μmol · l−1 · min−1) compared with those of the control subjects. HCLs and IMCLs were comparable between the MELAS patient and control subjects.
CONCLUSIONS Impairment of muscle mitochondrial fitness promotes insulin resistance and could thereby contribute to the development of diabetes in some patients with the MELAS syndrome.
Footnotes
-
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 November 18, 2008.
- Accepted December 26, 2008.
- © 2009 by the American Diabetes Association.
