IMR Press / FBL / Volume 14 / Issue 8 / DOI: 10.2741/3428

Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on imrpress.com as a courtesy and upon agreement with Frontiers in Bioscience.

Article
Therapeutic potential of SIRT1 and NAMPT-mediated NAD biosynthesis in type 2 diabetes
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1 Department of Developmental Biology, Washington University School of Medicine, St. Louis, MO 63110, USA
2 University Hospital for Children and Adolescents, University of Leipzig, Leipzig 04103, Germany
Front. Biosci. (Landmark Ed) 2009, 14(8), 2983–2995; https://doi.org/10.2741/3428
Published: 1 January 2009
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.

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