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 NAMPTmediated 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.
Original language | English |
---|---|
Pages (from-to) | 2983-2995 |
Number of pages | 13 |
Journal | Frontiers in Bioscience |
Volume | 14 |
Issue number | 8 |
DOIs | |
State | Published - Jan 1 2009 |
Keywords
- Adipose tissue
- Insulin secretion
- Insulin sensitivity
- Liver
- NAD biosynthesis
- NAMPT
- PBEF
- Pancreatic beta cells
- Review
- SIRT1
- Skeletal muscle
- Type 2 diabetes
- Visfatin