title: A single nucleotide polymorphism associates with the response of muscle ATP synthesis to long-term exercise training in relatives of type 2 diabetic humans.
abstract: OBJECTIVE
  Myocellular ATP synthesis (fATP) associates with insulin sensitivity in first-degree relatives of subjects with type 2 diabetes. Short-term endurance training can modify their fATP and insulin sensitivity. This study examines the effects of moderate long-term exercise using endurance or resistance training in this cohort.
  
  
  METHODS
  A randomized, parallel-group trial tested 16 glucose-tolerant nonobese relatives (8 subjects in the endurance training group and 8 subjects in the resistance training group) before and after 26 weeks of endurance or resistance training. Exercise performance was assessed from power output and oxygen uptake (VO(2)) during incremental tests and from maximal torque of knee flexors (MaxT(flex)) and extensors (MaxT(ext)) using isokinetic dynamometry. fATP and ectopic lipids were measured with (1)H/(31)P magnetic resonance spectroscopy.
  
  
  RESULTS
  Endurance training increased power output and VO(2) by 44 and 30%, respectively (both P < 0.001), whereas resistance training increased MaxT(ext) and MaxT(flex) by 23 and 40%, respectively (both P < 0.001). Across all groups, insulin sensitivity (382 ± 90 vs. 389 ± 40 mL · min(-1) · m(-2)) and ectopic lipid contents were comparable after exercise training. However, 8 of 16 relatives had 26% greater fATP, increasing from 9.5 ± 2.3 to 11.9 ± 2.4 μmol · mL(-1) · m(-1) (P < 0.05). Six of eight responders were carriers of the G/G single nucleotide polymorphism rs540467 of the NDUFB6 gene (P = 0.019), which encodes a subunit of mitochondrial complex I.
  
  
  CONCLUSIONS
  Moderate exercise training for 6 months does not necessarily improve insulin sensitivity but may increase ATP synthase flux. Genetic predisposition can modify the individual response of the ATP synthase flux independently of insulin sensitivity.
authors.affiliation: Karl-Landsteiner Institute for Endocrinology and Metabolism and 1st Medical Department, Hanusch Hospital, Vienna, Austria.
authors.forename: Gertrud
authors.initials: G
authors.lastname: Kacerovsky-Bielesz
authors.forename: Michaela
authors.initials: M
authors.lastname: Kacerovsky
authors.forename: Marek
authors.initials: M
authors.lastname: Chmelik
authors.forename: Michaela
authors.initials: M
authors.lastname: Farukuoye
authors.forename: Charlotte
authors.initials: C
authors.lastname: Ling
authors.forename: Rochus
authors.initials: R
authors.lastname: Pokan
authors.forename: Harald
authors.initials: H
authors.lastname: Tschan
authors.forename: Julia
authors.initials: J
authors.lastname: Szendroedi
authors.forename: Albrecht Ingo
authors.initials: AI
authors.lastname: Schmid
authors.forename: Stephan
authors.initials: S
authors.lastname: Gruber
authors.forename: Christian
authors.initials: C
authors.lastname: Herder
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: D000255:Adenosine Triphosphate / Q000378:metabolism*; D000328:Adult; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics* / Q000378:metabolism*; D042967:Electron Transport Complex I; D015444:Exercise / Q000502:physiology*; D005190:Family; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000378:metabolism*; D009247:NADH, NADPH Oxidoreductases / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D055070:Resistance Training
chemical_list: D000255:Adenosine Triphosphate; D009247:NADH, NADPH Oxidoreductases; D042967:Electron Transport Complex I; C527690:NDUFB6 protein, human