Kitada Munehiro, Koya Daisuke
Division of Diabetology and Endocrinology, Kanazawa Medical University, Kahoku, Japan.
Diabetes Metab J. 2013 Oct;37(5):315-25. doi: 10.4093/dmj.2013.37.5.315.
The prevalence of type 2 diabetes mellitus (T2DM) has been increasing worldwide. Therefore, a novel therapeutic strategy by which to prevent T2DM is urgently required. Calorie restriction (CR) can retard the aging processes, and delay the onset of numerous age-related diseases including diabetes. Metabolic CR mimetics may be therefore included as novel therapeutic targets for T2DM. Sirtuin 1 (SIRT1), a NAD(+)-dependent histone deacetylase that is induced by CR, is closely associated with lifespan elongation under CR. SIRT1 regulates glucose/lipid metabolism through its deacetylase activity on many substrates. SIRT1 in pancreatic β-cells positively regulates insulin secretion and protects cells from oxidative stress and inflammation, and has positive roles in the metabolic pathway via the modulation in insulin signaling. SIRT1 also regulates adiponectin secretion, inflammation, glucose production, oxidative stress, mitochondrial function, and circadian rhythms. Several SIRT1 activators, including resveratrol have been demonstrated to have beneficial effects on glucose homeostasis and insulin sensitivity in animal models of insulin resistance. Therefore, SIRT1 may be a novel therapeutic target for the prevention of T2DM, implicating with CR. In this review, we summarize current understanding of the biological functions of SIRT1 and discuss its potential as a promising therapeutic target for T2DM.
2型糖尿病（T2DM）在全球的患病率一直在上升。因此，迫切需要一种预防T2DM的新型治疗策略。热量限制（CR）可以延缓衰老过程，并延迟包括糖尿病在内的许多与年龄相关疾病的发病。因此，代谢性CR模拟物可能成为T2DM的新型治疗靶点。沉默调节蛋白1（SIRT1）是一种由CR诱导的NAD（+）依赖性组蛋白脱乙酰酶，与CR条件下的寿命延长密切相关。SIRT1通过其对许多底物的脱乙酰酶活性调节葡萄糖/脂质代谢。胰腺β细胞中的SIRT1正向调节胰岛素分泌，并保护细胞免受氧化应激和炎症的影响，且通过调节胰岛素信号在代谢途径中发挥积极作用。SIRT1还调节脂联素分泌、炎症、葡萄糖生成、氧化应激、线粒体功能和昼夜节律。包括白藜芦醇在内的几种SIRT1激活剂已被证明在胰岛素抵抗动物模型中对葡萄糖稳态和胰岛素敏感性具有有益作用。因此，SIRT1可能是预防T2DM的新型治疗靶点，与CR相关。在本综述中，我们总结了目前对SIRT1生物学功能的认识，并讨论了其作为T2DM有前景的治疗靶点的潜力。
