Metformin Impairs Mitochondrial Function in Skeletal Muscle of Both Lean and Diabetic Rats in a Dose-Dependent Manner

• DOI: 10.1371/journal.pone.0100525
• Publication Date: 2014-06-20T20:33:00Z
• Authors: Bart Wessels; Jolita Ciapaite; Nicole M. A. van ...; Klaas Nicolay; Jeanine J. Prompers
• Keywords: Ex vivo; Respirometry

Metformin is a widely prescribed drug for the treatment of type 2 diabetes. Previous studies have demonstrated in vitro that metformin specifically inhibits Complex I mitochondrial respiratory chain. This seems contraindicative since muscle dysfunction has been linked to pathogenesis However, its significance vivo skeletal function yet be elucidated. The aim this study was assess effects on and ex rat model Healthy (fa/+) diabetic (fa/fa) Zucker fatty rats were treated by oral gavage with dissolved water (30, 100 or 300 mg/kg bodyweight/day) as control weeks. After weeks treatment, oxidative capacity assessed using 31P magnetic resonance spectroscopy measuring oxygen consumption isolated mitochondria high-resolution respirometry. Two impaired dose-dependent manner, both healthy rats. Whereas dosage 30 mg/kg/day had no significant effect, 21% 48% lower after at mg/kg/day, respectively, independent genotype. High-resolution respirometry measurements similar effect function. In conclusion, compromises manner.