Therapeutic potential of SIRT1 and NAMPT-mediated NAD biosynthesis in type 2 diabetes.
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.
Imai
Shin-Ichiro
S
Department of Developmental Biology, Washington University School of Medicine, St. Louis, MO 63110, USA. imaishin@wustl.edu
Kiess
Wieland
W
D000375:Aging; D016207:Cytokines / Q000502:physiology*; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism* / Q000628:therapy; D006801:Humans; D007333:Insulin Resistance; D009243:NAD / Q000096:biosynthesis*; D054409:Nicotinamide Phosphoribosyltransferase / Q000502:physiology*; D056564:Sirtuin 1; D037761:Sirtuins / Q000502:physiology*
D016207:Cytokines; D009243:NAD; D054409:Nicotinamide Phosphoribosyltransferase; C085455:nicotinamide phosphoribosyltransferase, human; C447939:SIRT1 protein, human; D056564:Sirtuin 1; D037761:Sirtuins