Exercise improves glucose uptake in murine myotubes through the AMPKα2-mediated induction of Sestrins

In this study, we aim to better understand the relationship between SESNs and AMPK in response to exercise training and the possible mechanism by which SESNs mediate glucose metabolism. We used wild type, AMPKα2+/− and AMPKα2−/− C57BL/6 mice to reveal the pathway by which 6 weeks of exercise training induced SESNs. We explored the mechanism through which SESNs regulated glucose metabolism in vitro by overexpressing or inhibiting SESNs, and inhibiting AMPK or autophagy in myotubes. We found that a 6-week exercise training regime improved oxidative metabolism, activated the insulin signaling pathway and increased the level of SESN2 and SESN3 in an AMPKα2-dependent manner. Overexpression of SESN3 or SESN2 and SESN3 together increased glucose uptake, activated the insulin signaling pathway, and promoted GLUT4 translocation in myotubes. Although inhibition of SESNs had no effect on glucose uptake, SESNs could reverse reduced glucose uptake following autophagy inhibition, and may be downstream effectors of AMPK responses in myotubes. Taken together our data show that SESNs are induced by AMPKα2 after exercise training, and SESNs, specifically SESN3, play a key role in exercise training-mediated glucose metabolism in skeletal muscle.Graphical abstract
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - Category: Molecular Biology Source Type: research