Journal
DIABETES OBESITY & METABOLISM
Volume 15, Issue -, Pages 26-33Publisher
WILEY
DOI: 10.1111/dom.12171
Keywords
inflammation; insulin secretion; insulin sensitivity; NAD; NAD World; NAMPT; SIRT1
Categories
Funding
- National Institute on Ageing [AG024150, AG037457]
- National Heart, Lung, and Blood Institute [HL097817]
- Ellison Medical Foundation
- Longer Life Foundation
- Japan Research Foundation for Clinical Pharmacology
- Manpei Suzuki Diabetes Foundation
- Kanae Foundation for the Promotion of Medical Science
Ask authors/readers for more resources
Ageing is associated with a variety of pathophysiological changes, including development of insulin resistance, progressive decline in beta-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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available