Supplemental oxygen improves in vivo mitochondrial oxidative phosphorylation flux in sedentary obese adults with type 2 diabetes

Abstract

Type 2 diabetes is associated with impaired exercise capacity. Alterations in both muscle perfusion and mitochondrial function can contribute to exercise impairment. We hypothesized that impaired muscle mitochondrial function in type 2 diabetes is mediated, in part, by decreased tissue oxygen delivery and would improve with oxygen supplementation. Ex vivo muscle mitochondrial content and respiration assessed from biopsy samples demonstrated expected differences in obese individuals with (n = 18) and without (n = 17) diabetes. Similarly, in vivo mitochondrial oxidative phosphorylation capacity measured in the gastrocnemius muscle via 31 P-MRS indicated an impairment in the rate of ADP depletion with rest (27 6 6 s [diabetes], 21 6 7 s [control subjects]; P = 0.008) and oxidative phosphorylation (P = 0.046) in type 2 diabetes after isometric calf exercise compared with control subjects. Importantly, the in vivo impairment in oxidative capacity resolved with oxygen supplementation in adults with diabetes (ADP depletion rate 5.0 s faster, P = 0.012; oxidative phosphorylation 0.046 6 0.079 mmol/L/s faster, P = 0.027). Multiple in vivo mitochondrial measures related to HbA 1c . These data suggest that oxygen availability is rate limiting for in vivo mitochondrial oxidative exercise recovery measured with 31 P-MRS in individuals with uncomplicated diabetes. Targeting muscle oxygenation could improve exercise function in type 2 diabetes.