| First Author | Wang T | Year | 2018 |
| Journal | Biochim Biophys Acta Mol Basis Dis | Volume | 1864 |
| Issue | 10 | Pages | 3368-3377 |
| PubMed ID | 30048751 | Mgi Jnum | J:270617 |
| Mgi Id | MGI:6277506 | Doi | 10.1016/j.bbadis.2018.07.023 |
| Citation | Wang T, et al. (2018) Exercise improves glucose uptake in murine myotubes through the AMPKalpha2-mediated induction of Sestrins. Biochim Biophys Acta Mol Basis Dis 1864(10):3368-3377 |
| abstractText | Exercise training increases insulin sensitivity. Over the past decades, considerable progress has been made in understanding the molecular basis for this important effect of physical exercise. However, the underlying mechanism is still not fully described. Recent studies have revealed that the stress responsive protein family Sestrins (SESNs) may play an important role in improving insulin sensitivity of skeletal muscle under exercise training. 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, AMPKalpha2(+/-) and AMPKalpha2(-/-) C57BL/6 mice to reveal the pathway by which 6weeks 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 AMPKalpha2-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 AMPKalpha2 after exercise training, and SESNs, specifically SESN3, play a key role in exercise training-mediated glucose metabolism in skeletal muscle. |
