Insulin resistance has become a major global health problem, and current insulin sensitization treatments have the unfortunate effect of also increasing adiposity. One solution to mitigate these side effects would be to selectively stimulate skeletal muscle metabolism to reduce fasting glucose levels and improve insulin sensitivity. Previous studies have described growth differentiation factor 3 (GDF3) as an adipokine, however our recent studies have identified GDF3 as a macrophage derived factor that stimulates myoblast fusion and promotes muscle regeneration. Thus, we hypothesize that GDF3 might also stimulate myocyte metabolism and skeletal muscle insulin sensitivity. We first assessed whether recombinant GDF3 treatment can stimulate glucose uptake in vitro. Differentiated C2C12 myotubes were treated with rGDF3 and [H3] 2-deoxy-D-glucose uptake was found to be increased upon GDF3 treatment. Next, we tested whether GDF3 could stimulate insulin sensitivity in vivo. GDF3 was adenovirally overexpressed in mice fed a high fat diet for 8 weeks and insulin sensitivity was assessed by insulin tolerance tests. GDF3 overexpression reduced fasting glucose levels and also demonstrated a tendency for improved insulin tolerance. Collectively, these data suggest that GDF3 could act as a potential insulin sensitizing agent and provide mechanistic insights into skeletal muscle glucose regulation.
T.T. Hays: None. A. Patsalos: None. D. Hammers: None. C. Huang: None. I. Restrepo: None. M. Hajian: None. J. Ayala: None. L. Nagy: None.