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lüll Therapeutic potential of SIRT1 and NAMPT-mediated NAD biosynthesis in type 2 diabetes Imai S; Kiess WFront Biosci (Landmark Ed) 2009[Jan]; 14 (8): 2983-95Both 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.|Aging[MESH]|Cytokines/*physiology[MESH]|Diabetes Mellitus, Type 2/*metabolism/therapy[MESH]|Humans[MESH]|Insulin Resistance[MESH]|NAD/*biosynthesis[MESH]|Nicotinamide Phosphoribosyltransferase/*physiology[MESH]|Sirtuin 1[MESH]|Sirtuins/*physiology[MESH] |