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The Insulin-Sensitizing Effect of Rosiglitazone in Type 2 Diabetes Mellitus Patients Does Not Require Improved in Vivo Muscle Mitochondrial Function

Departments of Radiology (V.B.S.-H., M.E.K.) and Internal Medicine (J.-P.S.), Maastricht University Hospital, NL-6202 AZ Maastricht, The Netherlands; and Nutrition and Toxicology Research Institute Maastricht (V.B.S.-H., M.M., M.K.C.H., P.S.), and Departments of Human Biology (M.M., P.S.) and Human Movement Sciences (M.K.C.H.), Maastricht University, 6200 MD Maastricht, The Netherlands

Address all correspondence and requests for reprints to: Vera B. Schrauwen-Hinderling, Department of Radiology, Maastricht University Hospital, P.O. Box 5800, NL-6202 AZ Maastricht, The Netherlands. E-mail: v.schrauwen{at}hb.unimaas.nl.

Aims: 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.

Methods: Eight overweight type 2 diabetic patients (body mass index = 29.3 ± 1.1 kg/m²) 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.

Results: Insulin sensitivity improved after rosiglitazone (glucose infusion rate: 19.9 ± 2.8 to 24.8 ± 2.1 µmol/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 (R² = 0.50; P = 0.05) and glucose (R² = 0.43; P = 0.08) levels. Changes in PCr half-time did not correlate with changes in glucose infusion rate (R² = 0.08; P = 0.49).

Conclusion: The rosiglitazone-enhanced insulin sensitivity does not require improved muscular mitochondrial function.