ATP synthesis is impaired in isolated mitochondria from myotubes established from type 2 diabetic subjects

To date, it is unknown whether mitochondrial dysfunction in skeletal muscle from subjects with type 2 diabetes is based on primarily reduced mitochondrial mass and/or a primarily decreased mitochondrial ATP synthesis. Mitochondrial mass were determined in myotubes established from eight lean, eight obese and eight subjects with type 2 diabetes precultured under normophysiological conditions. Furthermore, mitochondria were isolated and ATP production was measured by luminescence at baseline and during acute insulin stimulation with or without concomitant ATP utilization by hexokinase. Mitochondrial mass and the ATP synthesis rate, neither at baseline nor during acute insulin stimulation, were not different between groups. The ratio of ATP synthesis rate at hexokinase versus ATP synthesis rate at baseline was lower in diabetic mitochondria compared to lean mitochondria. Thus the lower content of muscle mitochondria in type 2 diabetes in vivo is an adaptive trait and mitochondrial dysfunction in type 2 diabetes in vivo is based both on primarily impaired ATP synthesis and an adaptive loss of mitochondrial mass.

Research highlights
► The mitochondrial mass in myotubes established from lean, obese and T2D subjects was not significantly different.
► No primarily reduced ATP synthesis in isolated mitochondria from myotubes established from type 2 diabetic patient versus control patients at baseline and during insulin stimulation.
► Mitochondrial ATP synthesis were evaluated with or without concomitant ATP utilization by the hexokinase reaction catalyzing glucose 6-phosphate production from glucose and ATP.
► Lower ATP synthesis rate during ATP utilization in diabetic versus lean mitochondria.