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

Bart Wessels¹, Jolita Ciapaite¹, Klaas Nicolay¹, Jeanine Prompers¹

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.