Short-term exercise training does not stimulate skeletal muscle ATP synthesis in relatives of humans with type 2 diabetes.
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.
Kacerovsky-Bielesz
Gertrud
G
Medical Department, Hanusch Hospital, Vienna, Austria.
Chmelik
Marek
M
Ling
Charlotte
C
Pokan
Rochus
R
Szendroedi
Julia
J
Farukuoye
Michaela
M
Kacerovsky
Michaela
M
Schmid
Albrecht I
AI
Gruber
Stephan
S
Wolzt
Michael
M
Moser
Ewald
E
Pacini
Giovanni
G
Smekal
Gerhard
G
Groop
Leif
L
Roden
Michael
M
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*
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