The importance of NAMPT/NAD/SIRT1 in the systemic regulation of metabolism and ageing.
The importance of NAMPT/NAD/SIRT1 in the systemic regulation of metabolism and ageing.
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DOI：
10.1111/dom.12171
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发表时间：
2013-09
期刊：
影响因子：
--
通讯作者：
Yoshino J
中科院分区：
文献类型：
--
作者：
Imai S;Yoshino J
衰老与多种病理生理变化相关，包括胰岛素抵抗的发生、β细胞功能的进行性下降和慢性炎症，所有这些都会影响对营养和环境刺激的代谢稳态。SIRT1，哺乳动物的烟酰胺腺嘌呤二核苷酸（NAD）依赖性蛋白脱乙酰酶，和烟酰胺磷酸核糖转移酶（NAMPT），限速NAD生物合成酶，一起组成了一个新的系统性调控网络，命名为“NAD世界”，协调生理反应的内部和外部扰动，并保持哺乳动物的生理系统的鲁棒性。在过去的十年中，越来越多的证据表明，SIRT 1和NAMPT是NAD世界中的两个重要组成部分，在调节整个身体的胰岛素敏感性和胰岛素分泌方面发挥着关键作用。在这篇综述文章中，我们将总结SIRT1和NAMPT介导的NAD生物合成在代谢调节中的生理意义，并讨论功能层次和脆弱性在确定系统的鲁棒性方面的想法。我们还将讨论关键NAD中间体作为有效营养药物用于预防和治疗年龄相关代谢并发症（如2型糖尿病）的潜力。
Aging 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 review 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.
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影响因子：
4.2
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