Jiang Wei-jian
Department of Pharmacy, Guangzhou General Hospital of Guangzhou Military Command, 111 Liuhua Road, Guangzhou, Guangdong 510010, PR China.
Biochem Biophys Res Commun. 2008 Aug 29;373(3):341-4. doi: 10.1016/j.bbrc.2008.06.048. Epub 2008 Jun 23.
Calorie restriction extends lifespan and produces a metabolic profile desirable for treating diseases such as type 2 diabetes. SIRT1, an NAD(+)-dependent deacetylase, is a principal modulator of pathways downstream of calorie restriction that produces beneficial effects on glucose homeostasis and insulin sensitivity. Activation of SIRT1 leads to enhanced activity of multiple proteins, including peroxisome proliferator-activated receptor coactivator-1alpha (PGC-1alpha) and FOXO which helps to mediate some of the in vitro and in vivo effects of sirtuins. Resveratrol, a polyphenolic SIRT1 activator, mimics the effects of calorie restriction in lower organisms and in mice fed a high-fat diet ameliorates insulin resistance. In this review, we summarize recent research advances in unveiling the molecular mechanisms that underpin sirtuin as therapeutic candidates and discuss the possibility of using resveratrol as potential drug for treatment of diabetes.
热量限制可延长寿命，并产生有利于治疗2型糖尿病等疾病的代谢特征。SIRT1是一种依赖烟酰胺腺嘌呤二核苷酸（NAD⁺）的脱乙酰酶，是热量限制下游通路的主要调节因子，对葡萄糖稳态和胰岛素敏感性产生有益影响。SIRT1的激活导致多种蛋白质活性增强，包括过氧化物酶体增殖物激活受体共激活因子-1α（PGC-1α）和FOXO，它们有助于介导sirtuins在体外和体内的一些作用。白藜芦醇是一种多酚类SIRT1激活剂，在低等生物中模拟热量限制的作用，在喂食高脂饮食的小鼠中可改善胰岛素抵抗。在这篇综述中，我们总结了揭示sirtuins作为治疗候选分子机制的最新研究进展，并讨论了使用白藜芦醇作为治疗糖尿病潜在药物的可能性。
