Sirtuins Regulation In Diabetic Condition
Received Date: May 23, 2018 / Accepted Date: May 24, 2018 / Published Date: May 26, 2018
Sirtuins are NAD+ dependent enzymes having an ability to modify the structures of proteins and alter their functions by deacetylation activity. This property of sirtuins gave them much attention since past few years and their importance is growing in research rapidly among various multidisciplinary areas. Sirtuins regulate various diseases including diabetes, aging, heart failure and other metabolic disorders which results in growing interest of researchers in understanding the biology of these wonder molecules around the globe. In general, these are the protein deacetylases and weak mono ADP ribosyltransferases which action various histones and transcription factors . Sirtuins are considered as a switch that controls protein acetylation/deacetylation states and ultimately regulates various factors involved in different disease conditions associated with energy metabolism, aging and oxidative stress. Initially, most of the sirtuin research revolved around cancer biology but with time their importance is also unveiled in other disease conditions including diabetes.
Once considered as a rare disease with frequent urination , currently diabetes is one of the most common diseases across the globe. It has been estimated that 8.8% of world’s population between the age of 20 to 79 is diabetic . Unhealthy life style including food habits, less physical activities etc. and improper health facilities might be the main cause of the increase in diabetic population worldwide. For this reason, need for the new antidiabetic drug which could be able to target the root cause of the disease is crucial. Several recent studies suggest that physical exercise and calorie restriction improves the health conditions by activating a group of enzymes called sirtuins. Many research groups are in progress to understand the role and functions of these sirtuins. There are seven mammalian sirtuins (sirt1- sirt7) distributed in different subcellular compartments . Here is a brief description from the recent studies reflecting the importance of sirtuins in different disease conditions.
Recently published in 2018, a study by Bo et al. showed that sirt1 activation helps in maintaining redox homeostasis in the patients. In this study, they observed the effect of H3K56Ac levels in diabetic patients randomly selected to receive resveratrol or placebo for 6 months . Another study shows that exercise training in db/db+ mice increase sirt1 levels and improves inflammation markers like TNFalpha, IL-6, F4/80. It further improves the mitochondrial pathway axis of Sirt1/AMPK/PGC1-alpha and mitochondrial complex IV activities. Wananabe et al. reported that sirt2, the second member of human sirtuin family, is very crucial for hepatic glucose uptake . They showed that absence of sirt2 in the liver of non-diabetic mice causes glucose intolerance. Similarly, sirt2 overexpression in diabetic mice mitigates their impaired glucose tolerance and promotes hepatic glucose uptake by deacetylating K126 of glucokinase regulatory protein (GKRP) . Sirt3 is an NAD+ dependent mitochondrial sirtuin which improves mitochondrial health by controlling its dynamics. Recently, Sun et al. illustrates the importance of exogenous H2S and sirt3 in heart tissue of db/db mice. They showed that exogenous H2S increases the sirt3 expression by maintaining the NAD+/NADH ratio. It maintains the balance of acetylation level and different activities of the enzymes involved in the energy metabolism inside the cell. Ultimately, it does this by upregulating the sirt3 levels and by maintaining the balance between acetylation/ deacetylation activities . Another important study by Wood et al. described the role sirt4 in homeostasis. They showed that sirt4 knockout Drosophila flies are short-lived and not able to utilize energy reserves during starvation and ultimately causes death. This might have happened because of the defects in their metabolic pathways . Further exploring the importance of sirtuins, other analogue of sirtuin calledsirt6 is important for maintaining glucose homeostasis and insulin sensitivity. Sirt6 deficiency causes glucose intolerance and impaired glucose-stimulated insulin secretion. Qin et al. had shown that Sirt6 plays an important role in the normal functioning of beta cells via deacetylation of histone H3 and plays a critical role in maintaining beta cell function and viability. Sirt6 deficiency increases H3K9Ac, H3K56Ac levels and active RNA polymerase II at the promoter region of Txnip .
A number of evidence had shown the involvement of epigenetic regulation in different metabolic and vascular diseases. Like many other diseases, diabetes also showed the epigenetic variation in different human tissues. Hence, Importance of understanding the physiological and functional role of sirtuins can be understood by the fact that lot of debate is going on to find out and establish the potential epigenetic biomarker to identify the early risk and progression of diabetes.
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Citation: Kanwal A, Thaliath A (2018) Sirtuins Regulation In Diabetic Condition. Endocrinol Metab Syndr 7: e126. Doi: 10.4172/2161-1017.1000e126
Copyright: © 2018 Kanwal A, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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