Department of Systems Medicine, University of Rome "Tor Vergata", 00133 Rome, Italy.
Department of Biomedicine and Prevention, University of Rome Tor Vergata, 00133 Rome, Italy.
Int J Mol Sci. 2019 Sep 25;20(19):4748. doi: 10.3390/ijms20194748.
Sirtuins (SIRTs) are seven nicotinamide adenine dinucleotide (NAD)-dependent protein deacetylases enzymes (SIRT1-7) that play an important role in maintaining cellular homeostasis. Among those, the most studied are SIRT1 and SIRT3, a nuclear SIRT and a mitochondrial SIRT, respectively, which significantly impact with an increase in mammals' lifespan by modulating metabolic cellular processes. Particularly, when activated, both SIRT1 and 3 enhance pancreatic β-cells' insulin release and reduce inflammation and oxidative stress pancreatic damage, maintaining then glucose homeostasis. Therefore, SIRT1 and 3 activators have been proposed to prevent and counteract metabolic age-related diseases, such as type 2 diabetes mellitus (T2DM). Physical activity (PA) has a well-established beneficial effect on phenotypes of aging like β-cell dysfunction and diabetes mellitus. Recent experimental and clinical evidence reports that PA increases the expression levels of both SIRT1 and 3, suggesting that PA may exert its healthy contribute even by activating SIRTs. Therefore, in the present article, we discuss the role of SIRT1, SIRT3, and PA on β-cell function and on diabetes. We also discuss the possible interaction between PA and activation of SIRTs as a possible therapeutic strategy to maintain glucose hemostasis and to prevent T2DM and its complications, especially in the elderly population.
Sirtuins（SIRTs）是七种依赖烟酰胺腺嘌呤二核苷酸（NAD）的蛋白去乙酰化酶酶（SIRT1-7），它们在维持细胞内稳态方面发挥着重要作用。在这些 Sirtuins 中，研究最多的是 SIRT1 和 SIRT3，分别是核 SIRT 和线粒体 SIRT，它们通过调节代谢细胞过程显著影响哺乳动物寿命的延长。特别是，当被激活时，SIRT1 和 SIRT3 均能增强胰腺β细胞胰岛素的释放，并减少炎症和氧化应激对胰腺的损伤，从而维持血糖稳态。因此，SIRT1 和 SIRT3 的激活剂被提议用于预防和对抗与代谢相关的年龄相关疾病，如 2 型糖尿病（T2DM）。身体活动（PA）对β细胞功能和糖尿病等衰老表型具有明确的有益作用。最近的实验和临床证据表明，PA 会增加 SIRT1 和 SIRT3 的表达水平，这表明 PA 可能通过激活 SIRTs 发挥其健康作用。因此，在本文中，我们讨论了 SIRT1、SIRT3 和 PA 对β细胞功能和糖尿病的作用。我们还讨论了 PA 和 SIRTs 激活之间的可能相互作用，作为维持血糖稳态和预防 T2DM 及其并发症的一种可能的治疗策略，特别是在老年人群中。
