Exercise activates AMPK in mouse pancreatic islet leading to decreased senescence

Increased beta-cell senescence contributes to the development of type 2 diabetes (T2D). Exercise is critical in the treatment of T2D and can attenuate aging-associated cellular changes, but its effects on beta-cell senescence are unknown. Using two mouse models of insulin resistance, we showed that exercise prevented and reversed beta-cell senescence. Mechanistic studies revealed that these effects were mediated by exercise-induced increases in serum glucagon leading to AMPK activation in beta-cells. Nuclear translocation of NRF2 in mouse islets after exercise and its inversely proportional regulation of p16Ink4a, suggested its role as a molecular mediator between AMPK activation and cellular senescence.