Preprint Review Version 1 Preserved in Portico This version is not peer-reviewed

The Emerging role of HDACs: Pathology and Therapeutic targets in Diabetes Mellitus

Version 1 : Received: 27 April 2021 / Approved: 28 April 2021 / Online: 28 April 2021 (10:23:12 CEST)

How to cite: Dewanjee, S.; Vallamkondu, J.; Chakraborty, P.C.; Kalra, R.; Gangopadhyay, M.; Sahu, R.; Medala, V.; John, A.; Reddy, P.H.; Kandimalla, R. The Emerging role of HDACs: Pathology and Therapeutic targets in Diabetes Mellitus. Preprints 2021, 2021040742 (doi: 10.20944/preprints202104.0742.v1). Dewanjee, S.; Vallamkondu, J.; Chakraborty, P.C.; Kalra, R.; Gangopadhyay, M.; Sahu, R.; Medala, V.; John, A.; Reddy, P.H.; Kandimalla, R. The Emerging role of HDACs: Pathology and Therapeutic targets in Diabetes Mellitus. Preprints 2021, 2021040742 (doi: 10.20944/preprints202104.0742.v1).

Abstract

Diabetes mellitus (DM) is one of the principal manifestations of metabolic syndrome and its prevalence with modern lifestyle is increasing incessantly. Chronic hyperglycemia can induce several vascular complications that were referred to be the major cause of morbidity and mortality in DM. Although several therapeutic targets have been identified and accessed clinically, the imminent risk of DM and its prevalence are still ascending. Substantial pieces of evidence revealed that histone deacetylase (HDAC) isoforms can regulate various molecular activities in DM via epigenetic and post-translational regulation of several transcription factors. To date, 18 HDAC isoforms have been identified in mammals that were categorized into 4 different classes. Classes I, II, and IV are regarded as classical HDACs, which operate through a Zn-based mechanism. In contrast, class III HDACs or Sirtuins depend on nicotinamide adenine dinucleotide (NAD+) for their molecular activity. Functionally, most of the HDAC isoforms can regulate β cell fate, insulin release, insulin expression and signaling, and glucose metabolism. Moreover, the roles of HDAC members have been implicated in the regulation of oxidative stress, inflammation, apoptosis, fibrosis, and other pathological events, which substantially contribute to diabetes-related vascular dysfunctions. Therefore, HDACs could serve as the potential therapeutic target in DM towards developing novel intervention strategies. This review sheds light on the emerging role of HDACs/isoforms in diabetic pathophysiology and emphasized the scope of their targeting in DM for constituting the novel interventional strategies for metabolic disorders/complications.

Subject Areas

Diabetes mellitus; Glucose metabolism; Histone deacetylase; HDACs; Histone deacetylase inhibitor; HDACi, Insulin release; Sirtuins, Sirtuin activation

Comments (0)

We encourage comments and feedback from a broad range of readers. See criteria for comments and our diversity statement.

Leave a public comment
Send a private comment to the author(s)
Views 0
Downloads 0
Comments 0
Metrics 0


×
Alerts
Notify me about updates to this article or when a peer-reviewed version is published.
We use cookies on our website to ensure you get the best experience.
Read more about our cookies here.