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. RESEARCH DESIGN AND 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 26weeks of endurance or resistance training. Exercise performancewas assessed frompower output and oxygen uptake (VO 2) during incremental tests and frommaximal torque of knee flexors (MaxT flex) and extensors (MaxT ext) using isokinetic dynamometry. fATP and ectopic lipids were measured with 1H/ 31P 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 6 90 vs. 389 6 40 mL z 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 polymorphismrs540467 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. © 2012 by the American Diabetes Association.