Therapeutic potential of SIRT1 and NAMPT-mediated NAD biosynthesis in type 2 diabetes.

Abstract

Both genetic and environmental factors contribute to the pathogenesis of type 2 diabetes, and it is critical to understand the interplay between these factors in the regulation of insulin secretion and insulin sensitivity to develop effective therapeutic interventions for type 2 diabetes. For the past several years, studies on the mammalian NAD-dependent protein deacetylase SIRT1 and systemic NAD biosynthesis mediated by nicotinamide phosphoribosyltransferase (NAMPT) have demonstrated that these two regulatory components together play a critical role in the regulation of glucose homeostasis, particularly in the regulation of glucose-stimulated insulin secretion in pancreatic beta cells. These components also contribute to the age-associated decline in beta cell function, which has been suggested to be one of the major contributing factors to the pathogenesis of type 2 diabetes. In this review article, the roles of SIRT1 and NAMPT-mediated systemic NAD biosynthesis in glucose homeostasis and the pathophysiology of type 2 diabetes will be summarized, and their potential as effective targets for the treatment and prevention of type 2 diabetes will be discussed.

• Authors: Shin-Ichiro Imai, Wieland Kiess
• Journal: Frontiers in bioscience (Landmark edition) (Front Biosci (Landmark Ed)) Vol. 14 Issue 8 Pg. 2983-95 (01 01 2009) ISSN: 2768-6698 [Electronic] Singapore
• PMID: 19273250 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Review)

Chemical References

• Cytokines
• NAD
• Nicotinamide Phosphoribosyltransferase
• nicotinamide phosphoribosyltransferase, human
• SIRT1 protein, human
• Sirtuin 1
• Sirtuins

Topics

• Aging
• Cytokines (physiology)
• Diabetes Mellitus, Type 2 (metabolism, therapy)
• Humans
• Insulin Resistance
• NAD (biosynthesis)
• Nicotinamide Phosphoribosyltransferase (physiology)
• Sirtuin 1
• Sirtuins (physiology)