title: Short-term exercise training does not stimulate skeletal muscle ATP synthesis in relatives of humans with type 2 diabetes.
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.
  
  
  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.
authors.affiliation: Medical Department, Hanusch Hospital, Vienna, Austria.
authors.forename: Gertrud
authors.initials: G
authors.lastname: Kacerovsky-Bielesz
authors.forename: Marek
authors.initials: M
authors.lastname: Chmelik
authors.forename: Charlotte
authors.initials: C
authors.lastname: Ling
authors.forename: Rochus
authors.initials: R
authors.lastname: Pokan
authors.forename: Julia
authors.initials: J
authors.lastname: Szendroedi
authors.forename: Michaela
authors.initials: M
authors.lastname: Farukuoye
authors.forename: Michaela
authors.initials: M
authors.lastname: Kacerovsky
authors.forename: Albrecht I
authors.initials: AI
authors.lastname: Schmid
authors.forename: Stephan
authors.initials: S
authors.lastname: Gruber
authors.forename: Michael
authors.initials: M
authors.lastname: Wolzt
authors.forename: Ewald
authors.initials: E
authors.lastname: Moser
authors.forename: Giovanni
authors.initials: G
authors.lastname: Pacini
authors.forename: Gerhard
authors.initials: G
authors.lastname: Smekal
authors.forename: Leif
authors.initials: L
authors.lastname: Groop
authors.forename: Michael
authors.initials: M
authors.lastname: Roden
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000096:biosynthesis*; D017931:DNA Primers; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics* / Q000503:physiopathology; D042967:Electron Transport Complex I; D015444:Exercise; D005190:Family; D005247:Feeding Behavior; D006360:Heat-Shock Proteins / Q000235:genetics*; D006801:Humans; D018482:Muscle, Skeletal / Q000201:enzymology / Q000502:physiology*; D009247:NADH, NADPH Oxidoreductases / Q000235:genetics*; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D011110:Polymorphism, Genetic; D011795:Surveys and Questionnaires; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D017931:DNA Primers; D006360:Heat-Shock Proteins; C486497:PPARGC1A protein, human; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D014157:Transcription Factors; D000255:Adenosine Triphosphate; D009247:NADH, NADPH Oxidoreductases; D000251:Adenosine Triphosphatases; D042967:Electron Transport Complex I; C527690:NDUFB6 protein, human