Short-term exercise training does not stimulate skeletal muscle ATP synthesis in relatives of humans with type 2 diabetes

Abstract

Background We tested the hypothesis that short-term exercise training improves hereditary insulin resistance by stimulating ATP synthesis and investigated associations with gene polymorphisms.

Methods 24 nonobese first-degree relatives of type-2 diabetic patients and 12 controls were studied at rest and 48 hours after three bouts of exercise. In addition to measurements of oxygen uptake and insulin sensitivity (OGTT), ectopic lipids and mitochondrial ATP synthesis were assessed using ¹H and ³¹P magnetic resonance spectroscopy (MRS), 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 controls. In controls, ATP synthase flux rose by 18% (p=0.0001) being 23% higher (p=0.002) than 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), whereas “non-responders” failed to increase their insulin sensitivity. 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 O₂ uptake and insulin sensitivity.

Conclusions The ability of short-term exercise to stimulate ATP production distinguished individuals with improved insulin sensitivity from those who did not improve their insulin sensitivity. In addition, the NDUFB6 gene polymorphism appeared to modulate this adaptation. This suggests that genes involved in mitochondrial function contribute to the response of ATP synthesis to exercise training. This trial has been registered at ClinicalTrials.gov (NCT 00710008).