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The importance of NAMPT / NAD / SIRT1 in the systemic regulation of metabolism and ageing
Author(s) -
Imai S.,
Yoshino J.
Publication year - 2013
Publication title -
diabetes, obesity and metabolism
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.445
H-Index - 128
eISSN - 1463-1326
pISSN - 1462-8902
DOI - 10.1111/dom.12171
Subject(s) - nad+ kinase , nicotinamide phosphoribosyltransferase , nicotinamide adenine dinucleotide , biology , biochemistry , sirtuin 1 , insulin resistance , ageing , proteostasis , metabolism , microbiology and biotechnology , downregulation and upregulation , enzyme , insulin , endocrinology , genetics , gene
Ageing is associated with a variety of pathophysiological changes, including development of insulin resistance, progressive decline in β‐cell function and chronic inflammation, all of which affect metabolic homeostasis in response to nutritional and environmental stimuli. SIRT1, the mammalian nicotinamide adenine dinucleotide ( NAD )‐dependent protein deacetylase, and nicotinamide phosphoribosyltransferase ( NAMPT ), the rate‐limiting NAD biosynthetic enzyme, together comprise a novel systemic regulatory network, named the ‘ NAD World’, that orchestrates physiological responses to internal and external perturbations and maintains the robustness of the physiological system in mammals. In the past decade, an accumulating body of evidence has demonstrated that SIRT1 and NAMPT , two essential components in the NAD World, play a critical role in regulating insulin sensitivity and insulin secretion throughout the body. In this article, we will summarize the physiological significance of SIRT1 and NAMPT ‐mediated NAD biosynthesis in metabolic regulation and discuss the ideas of functional hierarchy and frailty in determining the robustness of the system. We will also discuss the potential of key NAD intermediates as effective nutriceuticals for the prevention and the treatment of age‐associated metabolic complications, such as type 2 diabetes.