SIRT1, a Calorie Restriction Mimetic, in a New Therapeutic Approach for Type 2 Diabetes Mellitus and Diabetic Vascular Complications

Shinji      Kume; Takashi      Uzu; Atsunori      Kashiwagi; Daisuke      Koya

Abstract

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.

Keywords: Diabetes, sirtuins, calorie restriction, CR mimetics, vascular complications, SIRT1 activator

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