Sirtuins and type 2 diabetes: Role in inflammation, oxidative stress and mitochondrial function
- 1Kanazawa Medical University, Japan
The rising incidence of type 2 diabetes mellitus (T2DM) is a major public health concern, and novel therapeutic strategies to prevent T2DM are urgently needed worldwide. Aging is recognized as one of the risk factors for metabolic impairments, including insulin resistance and T2DM. Inflammation, oxidative stress and mitochondrial dysfunction are closely related to both aging and metabolic disease. Calorie restriction (CR) can retard the aging process in organisms ranging from yeast to rodents and delay the onset of numerous age-related disorders, such as insulin resistance and diabetes. Therefore, metabolic CR mimetics may represent new therapeutic targets for insulin resistance and T2DM. Sirtuin 1 (SIRT1), the mammalian homolog of Sir2, was originally identified as a nicotinamide adenine dinucleotide (NAD+)-dependent histone deacetylase. The activation of SIRT1 is closely associated with longevity under CR, and it is recognized as a CR mimetic. Currently, seven sirtuins have been identified in mammals. Among these sirtuins, SIRT1 and SIRT2 are located in the nucleus and cytoplasm, SIRT3 exists predominantly in mitochondria, and SIRT6 is located in the nucleus. These sirtuins regulate metabolism through their regulation of inflammation, oxidative stress and mitochondrial function via multiple mechanisms, resulting in the improvement of insulin resistance and T2DM. In this review, we describe the current understanding of the biological functions of sirtuins, especially SIRT1, SIRT2, SIRT3 and SIRT6, focusing on oxidative stress, inflammation and mitochondrial function, which are closely associated with aging.
Keywords: SIRT1, SIRT2, SIRT6, type 2 diabetes, sirt3
Received: 22 Jul 2018;
Accepted: 06 Mar 2019.
Edited by:Ralf Jockers, Université Paris-Sorbonne, France
Reviewed by:Abdu Adem, United Arab Emirates University, United Arab Emirates
Houzao Chen, State Key Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, China
Sudhanshu Shukla, Amity Institute of Biotechnology, Amity University, India
Zhiping Liu, Augusta University, United States
Copyright: © 2019 Kitada, Ogura, Monno and Koya. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Dr. Munehiro Kitada, Kanazawa Medical University, Uchinada, Japan, firstname.lastname@example.org