Shukla AK, Awasthi K, Usman K, Banerjee M. Role of renin-angiotensin system/angiotensin converting enzyme-2 mechanism and enhanced COVID-19 susceptibility in type 2 diabetes mellitus. World J Diabetes 2024; 15(4): 606-622 [PMID: 38680697 DOI: 10.4239/wjd.v15.i4.606]
Corresponding Author of This Article
Monisha Banerjee, PhD, Professor, Molecular and Human Genetics Laboratory, Department of Zoology, University of Lucknow, University Road, Lucknow 226007, Uttar Pradesh, India. monishabanerjee30@gmail.com
Research Domain of This Article
Infectious Diseases
Article-Type of This Article
Review
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Ashwin Kumar Shukla, Komal Awasthi, Monisha Banerjee, Molecular and Human Genetics Laboratory, Department of Zoology, University of Lucknow, Lucknow 226007, Uttar Pradesh, India
Kauser Usman, Department of Medicine, King Georges’ Medical University, Lucknow 226003, Uttar Pradesh, India
Monisha Banerjee, Institute of Advanced Molecular Genetics, and Infectious Diseases (IAMGID), University of Lucknow, Lucknow 226007, Uttar Pradesh, India
Co-first authors: Ashwin K Shukla and Komal Awasthi.
Author contributions: Shukla AK and Awasthi K contributed equally to the study; Shukla AK contributed to the conceptualizing and writing; Awasthi K contributed to the conceptual writing of the manuscript; Usman K provided expert clinical input and interpretation of the reviewed literature; Banerjee M contributed to critical reading and reviewing the article and making critical revisions related to the intellectual content of the manuscript.
Conflict-of-interest statement: The authors declare having no conflicts of interest.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Monisha Banerjee, PhD, Professor, Molecular and Human Genetics Laboratory, Department of Zoology, University of Lucknow, University Road, Lucknow 226007, Uttar Pradesh, India. monishabanerjee30@gmail.com
Received: December 31, 2023 Peer-review started: December 31, 2023 First decision: January 16, 2024 Revised: January 22, 2024 Accepted: February 27, 2024 Article in press: February 27, 2024 Published online: April 15, 2024 Processing time: 102 Days and 11.6 Hours
Abstract
Coronavirus disease 2019 (COVID-19) is a disease that caused a global pandemic and is caused by infection of severe acute respiratory syndrome coronavirus 2 virus. It has affected over 768 million people worldwide, resulting in approximately 6900000 deaths. High-risk groups, identified by the Centers for Disease Control and Prevention, include individuals with conditions like type 2 diabetes mellitus (T2DM), obesity, chronic lung disease, serious heart conditions, and chronic kidney disease. Research indicates that those with T2DM face a heightened susceptibility to COVID-19 and increased mortality compared to non-diabetic individuals. Examining the renin-angiotensin system (RAS), a vital regulator of blood pressure and pulmonary stability, reveals the significance of the angiotensin-converting enzyme (ACE) and ACE2 enzymes. ACE converts angiotensin-I to the vasoconstrictor angiotensin-II, while ACE2 counters this by converting angiotensin-II to angiotensin 1-7, a vasodilator. Reduced ACE2 expression, common in diabetes, intensifies RAS activity, contributing to conditions like inflammation and fibrosis. Although ACE inhibitors and angiotensin receptor blockers can be therapeutically beneficial by increasing ACE2 levels, concerns arise regarding the potential elevation of ACE2 receptors on cell membranes, potentially facilitating COVID-19 entry. This review explored the role of the RAS/ACE2 mechanism in amplifying severe acute respiratory syndrome coronavirus 2 infection and associated complications in T2DM. Potential treatment strategies, including recombinant human ACE2 therapy, broad-spectrum antiviral drugs, and epigenetic signature detection, are discussed as promising avenues in the battle against this pandemic.
Core Tip: This manuscript explored the complex connection between type 2 diabetes mellitus and coronavirus disease 2019 (COVID-19), emphasizing the heightened susceptibility of diabetic individuals. It revealed the crucial involvement of the renin-angiotensin system and angiotensin converting enzyme (ACE)/ACE2 enzymes, clarifying how decreased ACE2 expression in diabetes amplifies renin-angiotensis system activity, contributing to inflammation and fibrosis. While ACE inhibitors exhibit therapeutic potential, concerns arise regarding their potential to facilitate viral entry. The review suggested that innovative approaches, including recombinant human ACE2 therapy and the detection of epigenetic signatures, present promising avenues for addressing COVID-19 and its complications in type 2 diabetes mellitus.
