The insulin-sensitizing effect of rosiglitazone in type 2 diabetes mellitus patients does not require improved in vivo muscle mitochondrial function.

Abstract

Our objective was to investigate whether improved in vivo mitochondrial function in skeletal muscle and intramyocellular lipids (IMCLs) contribute to the insulin-sensitizing effect of rosiglitazone. Eight overweight type 2 diabetic patients (body mass index = 29.3 +/- 1.1 kg/m(2)) were treated with rosiglitazone for 8 wk. Before and after treatment, insulin sensitivity was determined by a hyperinsulinemic euglycemic clamp. Muscular mitochondrial function (half-time of phosphocreatine recovery after exercise) and IMCL content were measured by magnetic resonance spectroscopy. Insulin sensitivity improved after rosiglitazone (glucose infusion rate: 19.9 +/- 2.8 to 24.8 +/- 2.1 micromol/kg.min; P < 0.05). In vivo mitochondrial function (phosphocreatine recovery half-time: 23.8 +/- 3.5 to 20.0 +/- 1.7 sec; P = 0.23) and IMCL content (0.93 +/- 0.18% to 1.37 +/- 0.40%; P = 0.34) did not change. Interestingly, the changes in PCr half-time correlated/tended to correlate with changes in fasting insulin (R(2) = 0.50; P = 0.05) and glucose (R(2) = 0.43; P = 0.08) levels. Changes in PCr half-time did not correlate with changes in glucose infusion rate (R(2) = 0.08; P = 0.49). The rosiglitazone-enhanced insulin sensitivity does not require improved muscular mitochondrial function.