title: Impaired mitochondrial function and insulin resistance of skeletal muscle in mitochondrial diabetes.
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 beta-cell mitochondria and secretion.
  
  
  METHODS
  We assessed muscular mitochondrial function and lipid deposition in liver (hepatocellular lipids [HCLs]) and muscle (intramyocellular lipids [IMCLs]) using (31)P/(1)H 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 x kg(-1) x 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 micromol x l(-1) x 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.
authors.affiliation: First Medical Department, Karl-Landsteiner Institute for Endocrinology and Metabolism, Hanusch Hospital, Vienna, Austria.
authors.forename: Julia
authors.initials: J
authors.lastname: Szendroedi
authors.forename: Albrecht Ingo
authors.initials: AI
authors.lastname: Schmid
authors.forename: Martin
authors.initials: M
authors.lastname: Meyerspeer
authors.forename: Camilla
authors.initials: C
authors.lastname: Cervin
authors.forename: Michaela
authors.initials: M
authors.lastname: Kacerovsky
authors.forename: Gerhard
authors.initials: G
authors.lastname: Smekal
authors.forename: Sabine
authors.initials: S
authors.lastname: Gräser-Lang
authors.forename: Leif
authors.initials: L
authors.lastname: Groop
authors.forename: Michael
authors.initials: M
authors.lastname: Roden
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D003920:Diabetes Mellitus / Q000503:physiopathology*; D004734:Energy Metabolism; D005260:Female; D005949:Glucose Oxidase; D019298:Glucose-6-Phosphate / Q000378:metabolism; D006339:Heart Rate; D006801:Humans; D007328:Insulin / Q000494:pharmacology; D007333:Insulin Resistance / Q000502:physiology*; D017241:MELAS Syndrome / Q000503:physiopathology*; D008930:Mitochondria, Liver / Q000187:drug effects / Q000502:physiology; D008931:Mitochondria, Muscle / Q000187:drug effects / Q000502:physiology*; D018482:Muscle, Skeletal / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology*; D012016:Reference Values; D013147:Spirometry
chemical_list: D001786:Blood Glucose; D007328:Insulin; D019298:Glucose-6-Phosphate; D000255:Adenosine Triphosphate; D005949:Glucose Oxidase