SIRT1 in Type 2 Diabetes: Mechanisms and Therapeutic Potential.
SIRT1 in Type 2 Diabetes: Mechanisms and Therapeutic Potential.
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DOI：
10.4093/dmj.2013.37.5.315
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发表时间：
2013-10
影响因子：
5.9
通讯作者：
Koya D
中科院分区：
文献类型：
--
作者：
Kitada M;Koya D
2型糖尿病（T2 DM）的患病率在全球范围内呈上升趋势。因此，迫切需要一种新的治疗策略来预防T2 DM。热量限制（CR）可以延缓衰老过程，并延缓包括糖尿病在内的许多与年龄相关的疾病的发生。因此，代谢CR模拟物可作为T2 DM的新型治疗靶点。Sirtuin 1（SIRT 1）是一种由CR诱导的NAD+依赖性组蛋白脱乙酰酶，与CR下的寿命延长密切相关。SIRT 1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SIRT 1正调节胰岛素分泌并保护细胞免受氧化应激和炎症，并且通过调节胰岛素信号传导在代谢途径中具有积极作用。SIRT 1还调节脂联素分泌、炎症、葡萄糖产生、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SIRT 1激活剂已被证明对胰岛素抵抗动物模型中的葡萄糖稳态和胰岛素敏感性具有有益作用。因此，SIRT 1可能成为预防T2 DM的一个新的治疗靶点，与CR有关。本文就SIRT 1的生物学功能及其作为T2 DM治疗靶点的研究进展作一综述。
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.