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SARS-CoV-2 Infections and ACE2: Clinical Outcomes Linked With Increased Morbidity and Mortality in Individuals With Diabetes
Individuals with diabetes suffering from coronavirus disease 2019 (COVID-19) exhibit increased morbidity and mortality compared with individuals without diabetes. In this Perspective, we critically evaluate and argue that this is due to a dysregulated renin-angiotensin system (RAS). Previously, we h...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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American Diabetes Association
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7458035/ https://www.ncbi.nlm.nih.gov/pubmed/32669391 http://dx.doi.org/10.2337/dbi20-0019 |
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author | Obukhov, Alexander G. Stevens, Bruce R. Prasad, Ram Li Calzi, Sergio Boulton, Michael E. Raizada, Mohan K. Oudit, Gavin Y. Grant, Maria B. |
author_facet | Obukhov, Alexander G. Stevens, Bruce R. Prasad, Ram Li Calzi, Sergio Boulton, Michael E. Raizada, Mohan K. Oudit, Gavin Y. Grant, Maria B. |
author_sort | Obukhov, Alexander G. |
collection | PubMed |
description | Individuals with diabetes suffering from coronavirus disease 2019 (COVID-19) exhibit increased morbidity and mortality compared with individuals without diabetes. In this Perspective, we critically evaluate and argue that this is due to a dysregulated renin-angiotensin system (RAS). Previously, we have shown that loss of angiotensin-I converting enzyme 2 (ACE2) promotes the ACE/angiotensin-II (Ang-II)/angiotensin type 1 receptor (AT1R) axis, a deleterious arm of RAS, unleashing its detrimental effects in diabetes. As suggested by the recent reports regarding the pathogenesis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), upon entry into the host, this virus binds to the extracellular domain of ACE2 in nasal, lung, and gut epithelial cells through its spike glycoprotein subunit S1. We put forth the hypothesis that during this process, reduced ACE2 could result in clinical deterioration in COVID-19 patients with diabetes via aggravating Ang-II–dependent pathways and partly driving not only lung but also bone marrow and gastrointestinal pathology. In addition to systemic RAS, the pathophysiological response of the local RAS within the intestinal epithelium involves mechanisms distinct from that of RAS in the lung; however, both lung and gut are impacted by diabetes-induced bone marrow dysfunction. Careful targeting of the systemic and tissue RAS may optimize clinical outcomes in subjects with diabetes infected with SARS-CoV-2. |
format | Online Article Text |
id | pubmed-7458035 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | American Diabetes Association |
record_format | MEDLINE/PubMed |
spelling | pubmed-74580352020-09-09 SARS-CoV-2 Infections and ACE2: Clinical Outcomes Linked With Increased Morbidity and Mortality in Individuals With Diabetes Obukhov, Alexander G. Stevens, Bruce R. Prasad, Ram Li Calzi, Sergio Boulton, Michael E. Raizada, Mohan K. Oudit, Gavin Y. Grant, Maria B. Diabetes Perspectives in Diabetes Individuals with diabetes suffering from coronavirus disease 2019 (COVID-19) exhibit increased morbidity and mortality compared with individuals without diabetes. In this Perspective, we critically evaluate and argue that this is due to a dysregulated renin-angiotensin system (RAS). Previously, we have shown that loss of angiotensin-I converting enzyme 2 (ACE2) promotes the ACE/angiotensin-II (Ang-II)/angiotensin type 1 receptor (AT1R) axis, a deleterious arm of RAS, unleashing its detrimental effects in diabetes. As suggested by the recent reports regarding the pathogenesis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), upon entry into the host, this virus binds to the extracellular domain of ACE2 in nasal, lung, and gut epithelial cells through its spike glycoprotein subunit S1. We put forth the hypothesis that during this process, reduced ACE2 could result in clinical deterioration in COVID-19 patients with diabetes via aggravating Ang-II–dependent pathways and partly driving not only lung but also bone marrow and gastrointestinal pathology. In addition to systemic RAS, the pathophysiological response of the local RAS within the intestinal epithelium involves mechanisms distinct from that of RAS in the lung; however, both lung and gut are impacted by diabetes-induced bone marrow dysfunction. Careful targeting of the systemic and tissue RAS may optimize clinical outcomes in subjects with diabetes infected with SARS-CoV-2. American Diabetes Association 2020-09 2020-07-15 /pmc/articles/PMC7458035/ /pubmed/32669391 http://dx.doi.org/10.2337/dbi20-0019 Text en © 2020 by the American Diabetes Association https://www.diabetesjournals.org/content/licenseReaders may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. More information is available at https://www.diabetesjournals.org/content/license. |
spellingShingle | Perspectives in Diabetes Obukhov, Alexander G. Stevens, Bruce R. Prasad, Ram Li Calzi, Sergio Boulton, Michael E. Raizada, Mohan K. Oudit, Gavin Y. Grant, Maria B. SARS-CoV-2 Infections and ACE2: Clinical Outcomes Linked With Increased Morbidity and Mortality in Individuals With Diabetes |
title | SARS-CoV-2 Infections and ACE2: Clinical Outcomes Linked With Increased Morbidity and Mortality in Individuals With Diabetes |
title_full | SARS-CoV-2 Infections and ACE2: Clinical Outcomes Linked With Increased Morbidity and Mortality in Individuals With Diabetes |
title_fullStr | SARS-CoV-2 Infections and ACE2: Clinical Outcomes Linked With Increased Morbidity and Mortality in Individuals With Diabetes |
title_full_unstemmed | SARS-CoV-2 Infections and ACE2: Clinical Outcomes Linked With Increased Morbidity and Mortality in Individuals With Diabetes |
title_short | SARS-CoV-2 Infections and ACE2: Clinical Outcomes Linked With Increased Morbidity and Mortality in Individuals With Diabetes |
title_sort | sars-cov-2 infections and ace2: clinical outcomes linked with increased morbidity and mortality in individuals with diabetes |
topic | Perspectives in Diabetes |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7458035/ https://www.ncbi.nlm.nih.gov/pubmed/32669391 http://dx.doi.org/10.2337/dbi20-0019 |
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