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Diabetes Obes Metab. 2013 Sep;15 Suppl 3:26-33. doi: 10.1111/dom.12171.

The importance of NAMPT/NAD/SIRT1 in the systemic regulation of metabolism and ageing.

Author information

1
Department of Developmental Biology, Washington University School of Medicine, St. Louis, MO 63110, USA. imaishin@wustl.edu

Abstract

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.

KEYWORDS:

NAD; NAD World; NAMPT; SIRT1; inflammation; insulin secretion; insulin sensitivity

PMID:
24003918
PMCID:
PMC3819727
DOI:
10.1111/dom.12171
[Indexed for MEDLINE]
Free PMC Article

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