Beta (β)-cell senescence contributes to type 2 diabetes mellitus (T2DM). While exercise is vital for T2DM management and significantly affects cellular ageing markers, its effect on β-cell senescence remains unexplored. Here, we show that short-term endurance exercise training (treadmill running, 1 h per day for 10 days) in two male and female mouse models of insulin resistance decreases β-cell senescence. In vivo and in vitro experiments revealed that this effect is mediated, at least in part, by training-induced increases in serum glucagon, leading to activation of 5′-AMP-activated protein kinase (AMPK) signalling in β-cells. AMPK activation resulted in the nuclear translocation of NRF2 and decreased expression of senescence markers and effectors. Remarkably, human islets from male and female donors with T2DM treated with serum collected after a 10-week endurance exercise training programme showed a significant decrease in the levels of senescence markers. These findings indicate that exercise training decreases senescence in pancreatic islets, offering promising therapeutic implications for T2DM.

β （β） 细胞衰老导致 2 型糖尿病 （T2DM）。虽然运动对 T2DM 管理至关重要并显着影响细胞衰老标志物，但其对 β 细胞衰老的影响仍未得到探索。在这里，我们表明，在两种雄性和雌性胰岛素抵抗小鼠模型中，短期耐力运动训练（跑步机跑步，每天 1 小时，持续 10 天）可减少β细胞衰老。体内和体外实验表明，这种作用至少部分是由训练诱导的血清胰高血糖素增加介导的，导致 β 细胞中 5′-AMP 活化蛋白激酶 （AMPK） 信号的激活。AMPK 激活导致 NRF2 的核转位并降低衰老标志物和效应子的表达。值得注意的是，在为期 10 周的耐力运动训练计划后收集的血清处理的 T2DM 男性和女性供体的人类胰岛显示衰老标志物水平显着降低。这些发现表明，运动训练可减少胰岛的衰老，为 T2DM 提供有希望的治疗意义。