Meeting Abstract
J.L. Ochab, A.J. Koenig, S.T. Kinsey The University of North Carolina Wilmington jlo3999@uncw.edu The effects of metformin on skeletal muscle differentiation and fusion AMP activated protein kinase (AMPK) functions as a cellular energy sensor and it is a target for the treatment of obesity and type II diabetes. Activation of AMPK has well-known benefits such as increased fuel oxidation and enhanced insulin sensitivity, however, it also may lead to compromised satellite cell function. This may be particularly detrimental to muscle development in juveniles, when satellite cell density and activity is high. In this study, the type II diabetic drug metformin was used to pharmacologically activate AMPK in C2C12 mouse skeletal muscle myoblasts and in juvenile mice. Myocytes and early myotubes treated with 1mM metformin had a decreased expression of the myogenic marker, myogenin, but there was no difference in the expression of the adhesion molecule NCAM. Laser scanning confocal microscopy demonstrated that metformin-treated cells in mid-late differentiation also had decreased cell-cell membrane fusion. These results were consistent with a reduced gastrocnemius mass in juvenile mice treated with metformin. Further gastrocnemius muscle from mice treated with metformin had a reduced expression of the satellite cell marker, Pax7, as well as the myogenic markers, myogenin, MyoD, and NCAM. Together, the in vitro and in vivo results support the hypothesis that AMPK activation with metformin inhibits muscle development by interfering with satellite cell differentiation and fusion.
