RT Journal Article
SR Electronic
T1 Short-Term Exercise Training Does Not Stimulate Skeletal Muscle ATP Synthesis in Relatives of Humans With Type 2 Diabetes
JF Diabetes
JO Diabetes
FD American Diabetes Association
SP 1333
OP 1341
DO 10.2337/db08-1240
VO 58
IS 6
A1 Kacerovsky-Bielesz, Gertrud
A1 Chmelik, Marek
A1 Ling, Charlotte
A1 Pokan, Rochus
A1 Szendroedi, Julia
A1 Farukuoye, Michaela
A1 Kacerovsky, Michaela
A1 Schmid, Albrecht I.
A1 Gruber, Stephan
A1 Wolzt, Michael
A1 Moser, Ewald
A1 Pacini, Giovanni
A1 Smekal, Gerhard
A1 Groop, Leif
A1 Roden, Michael
YR 2009
UL http://diabetes.diabetesjournals.org/content/58/6/1333.abstract
AB OBJECTIVE We tested the hypothesis that short-term exercise training improves hereditary insulin resistance by stimulating ATP synthesis and investigated associations with gene polymorphisms. RESEARCH DESIGN AND 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 using1H and31P 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 O2uptake 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.