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.