Insulin induces structural changes leading to muscle hypertrophy. Skeletal muscle differentiation is orchestrated by myogenic regulator factors (MRFs) and late myogenic protein MyHC (myosin heavy chain). Metformin (Met) is a first-line anti-diabetic therapy.

Aim of this work is to study in vitro and in vivo the action of Met during myogenesis. We used C2C12 muscle cell model to investigate muscle proteosynthesis pathways and morphologic characteristics. After 72h of differentiation, C2C12 were incubated with 400 mM Met for 30 min, 2 and 4 hours. We used positive control with 0.1 nM insulin added to medium and negative control in which Met and insulin were not added.

By Western Blot and Immunofluorescence studies we observed that Met raises MRFs proteins content,cell massand fusion competence. These data indicate that Met may regulate myogenesis and fibers hypertrophy.

To test those results in vivo, we investigated the action of Met on exercise performance in adult C57BL/6 mice. Mice were injected intra abdominally with Met (250 mg/kg) and the control mice with 0.9% saline for 30 days.An endurance performance treadmill running test made at the beginning and at the end of this study revealed that Met treated mice exhibit an enhanced performance respect to the control mice (VO_2max ml/kg^0.75per min: Met 14.41 ± 1.5 respect to control 12.6 ± 2.8).

Ourfindings show a novel therapeutic indication of metformin for muscle hypotrophy in chronic wasting diseases.