Open Access
Article
Therapeutic potential of SIRT1 and NAMPT-mediated NAD biosynthesis in type 2 diabetes
Shin-Ichiro Imai1,Wieland Kiess1
1
Department of Developmental Biology, Washington University School of Medicine, St. Louis, MO 63110, USA. imaishin@wustl.edu
DOI: 10.2741/3428 Volume 14 Issue 8, pp.2983-2995
Published: 01 January 2009
(This article belongs to the Special Issue New therapeutic approaches for 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.

Share and Cite
Shin-Ichiro Imai, Wieland Kiess. Therapeutic potential of SIRT1 and NAMPT-mediated NAD biosynthesis in type 2 diabetes. Frontiers in Bioscience-Landmark. 2009. 14(8); 2983-2995.