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Abstract #3267

Metformin Severely Impairs In Vivo Muscle Oxidative Capacity in a Rat Model of Type 2 Diabetes

Bart Wessels1, Jolita Ciapaite1, Klaas Nicolay1, Jeanine Prompers1

1Biomedical NMR, Eindhoven University of Technology, Eindhoven, Netherlands

In this study we investigated the effect of the anti-diabetic drug metformin on in vivo and in vitro skeletal muscle mitochondrial function in Zucker diabetic fatty (ZDF) rats using 31P magnetic resonance spectroscopy (MRS) and high-resolution respirometry, respectively. In vivo dynamic 31P MRS demonstrated that two weeks of treatment with metformin severely impairs in vivo muscle oxidative capacity both in diabetic and healthy ZDF rats. In vitro complex I-supported respiration was only reduced in the diabetic group. The 2-fold decrease in in vivo muscle oxidative capacity could therefore not be fully attributed to metformins inhibitory effect on mitochondrial complex I.