A discordance in rosiglitazone mediated insulin sensitization and skeletal muscle mitochondrial content/activity in Type 2 diabetes mellitus.

Skeletal muscle mitochondrial dysfunction is hypothesized to contribute to the pathophysiology of insulin resistance and Type 2 diabetes. Whether thiazolidinedione therapy enhances skeletal muscle mitochondrial function as a component of its insulin-sensitizing effect is unknown. To test this, we evaluated skeletal muscle mitochondria and exercise capacity in Type 2 diabetic subjects with otherwise normal cardiopulmonary function in response to rosiglitazone therapy. Twenty-three subjects were treated for 12 wk and underwent pre- and posttherapy metabolic stress testing and skeletal muscle biopsies. Rosiglitazone significantly ameliorated fasting glucose, insulin, and free fatty acid levels but did not augment the subjects' maximal oxygen consumption (Vo2max) or their skeletal muscle mitochondrial copy number. The baseline Vo2max correlated strongly with muscle mitochondrial copy number (r = 0.56, P = 0.018, n = 17) and inversely with the duration of diabetes (r = −0.67, P = 0.004, n = 23). Despite the ...