Kume Shinji, Uzu Takashi, Kashiwagi Atsunori, Koya Daisuke
Department of Medicine, Shiga University of Medical Science, Otsu, Japan.
Endocr Metab Immune Disord Drug Targets. 2010 Mar;10(1):16-24. doi: 10.2174/187153010790827957.
The rising incidence of diabetes, metabolic syndrome, and subsequent vascular diseases is now a major public health problem in industrialized countries. New therapeutic strategies to prevent these diseases are urgently needed worldwide. It is well known that calorie restriction (CR) can retard the aging process in organisms ranging from yeast to rodents, and delay the onset of numerous age-related diseases including diabetes. Molecules that mimic CR metabolically are therefore potentially new therapeutic targets for age-related diseases. Silent information regulator 2 (Sir2) is an important player in CR-mediated life span extension. There is also increasing evidence that one of the seven mammalian sirtuins, SIRT1, is involved in regulating cellular processes such as apoptosis. SIRT1 has also been implicated in glucose homeostasis and lipid metabolism in various tissues including adipose tissues, liver, pancreas, and skeletal muscle. This review summarizes current understanding of the biological functions of SIRT1, and discusses its potential as a pharmacological target for fighting metabolic and vascular diseases.
糖尿病、代谢综合征以及随之而来的血管疾病发病率不断上升，这已成为工业化国家的一个主要公共卫生问题。全球迫切需要新的治疗策略来预防这些疾病。众所周知，热量限制（CR）可以延缓从酵母到啮齿动物等生物体的衰老过程，并延缓包括糖尿病在内的多种与年龄相关疾病的发病。因此，代谢上模拟CR的分子可能是与年龄相关疾病的新治疗靶点。沉默信息调节因子2（Sir2）是CR介导的寿命延长中的一个重要参与者。越来越多的证据表明，七种哺乳动物沉默调节蛋白之一的SIRT1参与调节细胞凋亡等细胞过程。SIRT1还与包括脂肪组织、肝脏、胰腺和骨骼肌在内的各种组织中的葡萄糖稳态和脂质代谢有关。本综述总结了目前对SIRT1生物学功能的认识，并讨论了其作为对抗代谢和血管疾病的药理学靶点的潜力。
