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

Front Biosci (Landmark Ed). 2009 Jan 1;14:2983-95. doi: 10.2741/3428.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

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

Substances

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