Sirtuins: novel targets for metabolic disease in drug development.
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.
Jiang
Wei-jian
WJ
Department of Pharmacy, Guangzhou General Hospital of Guangzhou Military Command, 111 Liuhua Road, Guangzhou, Guangdong 510010, PR China. sumscn@yahoo.com
D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D031204:Caloric Restriction; D003920:Diabetes Mellitus / Q000188:drug therapy* / Q000201:enzymology*; D015195:Drug Design; D004789:Enzyme Activation; D006801:Humans; D007328:Insulin / Q000378:metabolism; D008297:Male; D051379:Mice; D051381:Rats; D000077185:Resveratrol; D015398:Signal Transduction; D056564:Sirtuin 1; D037761:Sirtuins / Q000819:agonists* / Q000235:genetics / Q000378:metabolism; D013267:Stilbenes / Q000627:therapeutic use*; D013379:Substrate Specificity
D000975:Antioxidants; D007328:Insulin; D013267:Stilbenes; C447939:SIRT1 protein, human; D056564:Sirtuin 1; D037761:Sirtuins; D000077185:Resveratrol