Effect of physical training on mitochondrial function in skeletal muscle of normal and diabetic rats

The study was designed to assess the impact of physical training on the oxidative phosphorylation rate (OPR) in mitochondria isolated from two different skeletal muscles of rats with or without chronic diabetes mellitus. Diabetes was induced by an intravenous injection of streptozotocin (50 mg/kg), and only animals with a blood glucose level between 14 and 22 mmol/L 1 week later were kept in the protocol. Exercise training was performed on a treadmill with a progressive 10-week program. Rats were killed by decapitation at the end of the training program, and mitochondria were isolated from the gastrocnemius and the red vastus lateralis muscles. When the data were expressed as per milligrams of protein, OPR was significantly depressed by diabetes mellitus in the mitochondria from each muscle; a similar negative impact also appeared to be produced by physical training in mitochondria isolated from the red vastus lateralis muscle. However, due to changes in mitochondrial protein yield between groups, the capacity to oxidize pyruvate and malate was also calculated per gram of muscle. Adenosine triphosphate (ATP) production rate appeared to be unaffected by diabetes but significantly increased by training in both muscles of diabetic and nondiabetic rats. This effect of training was not associated with any improvement in plasma glucose or insulin levels in diabetic animals. However, the large increase in plasma levels of beta-hydroxybutyric acid in sedentary diabetic rats was partly reversed by training (1,079 +/- 472 v 3,424 +/- 618 micromol, P < .001). These results suggest that the training-induced increase in the capacity of skeletal muscles to oxidize substrates and generate energy may also contribute to reduce the elevated plasma beta-hydroxybutyric acid levels observed in a state of insulin deficiency. This may have clinical relevance, since ketoacidosis remains a life-threatening event in insulin-dependent diabetic subjects.