Sirtuins: novel targets for metabolic disease in drug development.

Full Abstract

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.

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Author information

Author/s: Jiang, Wei-jian (WJ);

Affiliation: Department of Pharmacy, Guangzhou General Hospital of Guangzhou Military Command, 111 Liuhua Road, Guangzhou, Guangdong 510010, PR China. sumscn(-atsign-)yahoo.com

Journal and publication information

Publication Type: Journal Article; Review

Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun), published in United States. (Language: eng)

Reference: 2008-Aug; vol 373 (issue 3) : pp 341-4

Dates: Created 2008/07/22; Completed 2008/08/06;

PMID: 18577374, status: MEDLINE (last retrieval date: 11/6/2008)

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Animals
Antioxidants - therapeutic use
Caloric Restriction
Diabetes Mellitus - drug therapy; enzymology
Drug Design
Enzyme Activation
Humans
Insulin - metabolism

Insulin - metabolism
Male
Mice
Rats
Signal Transduction
Sirtuins - agonists; genetics; metabolism
Stilbenes - therapeutic use
Substrate Specificity

Associated Chemicals: Antioxidants (0) ; Stilbenes (0) ; Insulin (11061-68-0) ; resveratrol (501-36-0) ; SIRT1 protein, human (EC 3.5.1.-) ; Sirtuins (EC 3.5.1.-)

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