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Open Access 01-09-2020 | SARS-CoV-2 | Commentary

ACE2 and SARS-CoV-2 Infection: Might GLP-1 Receptor Agonists Play a Role?

Authors: Vincenzo M. Monda, Francesca Porcellati, Felice Strollo, Sandro Gentile

Published in: Diabetes Therapy | Issue 9/2020

Excerpt

Recently it has been hypothesized that DPP4 inhibitors can have a beneficial effect on SARS-CoV-2 infection through immunoregulating activity.

Experimental study on streptozotocin-treated rats showed that liraglutide was able to stimulate the expression of pulmonary angiotensin converting enzyme 2 (ACE2) and angiotensin (1–7).

Liraglutide modulated different elements of the renin angiotensin system (RAS), significantly increasing ACE2 and Mas receptor (MasR) mRNA expression in pup lungs from food-restricted mothers.

Some action mechanisms support the hypothesis of a protective action of GLP-1R agonists, capable of mitigating a more serious clinical course among SARS-CoV-2-infected individuals with T2DM.

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Lu R, Zhao X, Li J, et al. Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. Lancet. 2020;395(10224):565–74. https://doi.org/10.1016/S0140-6736(20)30251-8.CrossRefPubMedPubMedCentral

Chan-Yeung M, Xu RH. SARS: epidemiology. Respirology. 2003;8(suppl):S9–14. https://doi.org/10.1046/j.1440-1843.2003.00518.x.CrossRefPubMedPubMedCentral

WHO Middle East respiratory syndrome coronavirus (MERS-CoV). https://www.who.int/emergencies/mers-cov/en/. Accessed 16 Jan 2018.

Raj VS, Mou H, Smits SL, et al. Dipeptidyl peptidase 4 is a functional receptor for the emerging human coronavirus-EMC. Nature. 2013;495(7440):251–4. https://doi.org/10.1038/nature12005.CrossRefPubMedPubMedCentral

Lovshin JA, Drucker DJ. Incretin-based therapies for type 2 diabetes mellitus. Nat Rev Endocrinol. 2009;5(5):262–9. https://doi.org/10.1038/nrendo.2009.48.CrossRefPubMed

Martin JH, Deacon CF, Gorrell MD, Prins JB. Incretin-based therapies—review of the physiology, pharmacology and emerging clinical experience. Intern Med J. 2011;41(4):299–307. https://doi.org/10.1111/j.1445-5994.2011.02439.x.CrossRefPubMed

Hedrington MS, Davis SN. Oral semaglutide for the treatment of type 2 diabetes. Expert Opin Pharmacother. 2019;20(2):133–41. https://doi.org/10.1080/14656566.2018.155225.CrossRefPubMed

Iacobellis G. COVID-19 and diabetes: can DPP-IV inhibition play a role? Diabetes Res Clin Pract. 2020;162:108125. https://doi.org/10.1016/j.diabres.2020.108125.CrossRefPubMedPubMedCentral

Tianru J. Letter to the editor: Comment on GLP-1-based drugs and COVID-19 treatment. Acta Pharm Sin B. 2020. https://doi.org/10.1016/j.apsb.2020.05.006.CrossRef

10.

Drucker DJ. Coronavirus infections and type 2 diabetes-shared pathways with therapeutic implications. Endocr Rev. 2020;41(3):bnaa011. https://doi.org/10.1210/endrev/bnaa011.CrossRefPubMed

11.

Mirabelli M, Chiefari E, Puccio L, Foti DP, Brunetti A. Potential benefits and harms of novel antidiabetic drugs during COVID-19 crisis. Int J Environ Res Public Health. 2020;17(10):3664. https://doi.org/10.3390/ijerph17103664.CrossRefPubMedCentral

12.

Lee YS, Jun HS. Anti-inflammatory effects of GLP-1-based therapies beyond glucose control. Mediators Inflamm. 2016;2016:3094642. https://doi.org/10.1155/2016/3094642.CrossRefPubMedPubMedCentral

13.

Romaní-Pérez M, Outeiriño-Iglesias V, Moya CM, et al. Activation of the GLP-1 receptor by liraglutide increases ACE2 expression, reversing right ventricle hypertrophy, and improving the production of SP-A and SP-B in the lungs of type 1 diabetes rats. Endocrinology. 2015;156(10):3559–69. https://doi.org/10.1210/en.2014-1685.CrossRefPubMed

14.

Fandiño J, Vaz AA, Toba L, et al. Liraglutide enhances the activity of the ACE-2/Ang(1–7)/Mas receptor pathway in lungs of male pups from food-restricted mothers and prevents the reduction of SP-A. Int J Endocrinol. 2018;2018:6920620. https://doi.org/10.1155/2018/6920620.CrossRefPubMedPubMedCentral

15.

Wösten-van Asperen RM, Lutter R, Specht PA, et al. Acute respiratory distress syndrome leads to reduced ratio of ACE/ACE2 activities and is prevented by angiotensin-(1–7) or an angiotensin II receptor antagonist. J Pathol. 2011;225(4):618–27. https://doi.org/10.1002/path.2987.CrossRefPubMed

16.

Kuba K, Imai Y, Rao S, Jiang C, Penninger JM. Lessons from SARS: control of acute lung failure by the SARS receptor ACE2. J Mol Med (Berl). 2006;84(10):814–20. https://doi.org/10.1007/s00109-006-0094-9.CrossRef

17.

Verdecchia P, Cavallini C, Spanevello A, Angeli F. The pivotal link between ACE2 deficiency and SARS-CoV-2 infection. Eur J Intern Med. 2020. https://doi.org/10.1016/j.ejim.2020.04.037.CrossRefPubMedPubMedCentral

18.

Santos RAS, Sampaio WO, Alzamora AC, et al. The ACE2/Angiotensin-(1–7)/MAS axis of the renin-angiotensin system: focus on angiotensin-(1–7). Physiol Rev. 2018;98(1):505–53. https://doi.org/10.1152/physrev.00023.2016.CrossRefPubMed

19.

Fang C, Stavrou E, Schmaier AA, et al. Angiotensin 1–7 and Mas decrease thrombosis in Bdkrb2-/- mice by increasing NO and prostacyclin to reduce platelet spreading and glycoprotein VI activation. Blood. 2013;121(15):3023–32. https://doi.org/10.1182/blood-2012-09-459156(published correction appears in Blood. 2014 Mar 6;123(10):1622).CrossRefPubMedPubMedCentral

20.

Celi A, Cianchetti S, Dell'Omo G, Pedrinelli R. Angiotensin II, tissue factor and the thrombotic paradox of hypertension. Expert Rev Cardiovasc Ther. 2010;8(12):1723–9. https://doi.org/10.1586/erc.10.161.CrossRefPubMed

21.

Benigni A, Cassis P, Remuzzi G. Angiotensin II revisited: new roles in inflammation, immunology and aging. EMBO Mol Med. 2010;2(7):247–57. https://doi.org/10.1002/emmm.201000080.CrossRefPubMedPubMedCentral

22.

Gheblawi M, Wang K, Viveiros A, et al. Angiotensin-converting enzyme 2: SARS-CoV-2 receptor and regulator of the renin-angiotensin system: celebrating the 20th anniversary of the discovery of ACE2. Circ Res. 2020;126(10):1456–74. https://doi.org/10.1161/CIRCRESAHA.120.317015.CrossRefPubMed

23.

Helms J, Tacquard C, Severac F, et al. High risk of thrombosis in patients with severe SARS-CoV-2 infection: a multicenter prospective cohort study. Intensive Care Med. 2020;46(6):1089–98. https://doi.org/10.1007/s00134-020-06062-x.CrossRefPubMedPubMedCentral

24.

Wright JR. Immunoregulatory functions of surfactant proteins. Nat Rev Immunol. 2005;5(1):58–68.CrossRefPubMed

25.

Hashimoto T, Perlot T, Rehman A, et al. ACE2 links amino acid malnutrition to microbial ecology and intestinal inflammation. Nature. 2012;487(7408):477–81. https://doi.org/10.1038/nature11228.CrossRefPubMedPubMedCentral

26.

Zhang H, Penninger JM, Li Y, Zhong N, Slutsky AS. Angiotensin-converting enzyme 2 (ACE2) as a SARS-CoV-2 receptor: molecular mechanisms and potential therapeutic target. Intensive Care Med. 2020;46:586–90. https://doi.org/10.1007/s00134-020-05985-9.CrossRefPubMedPubMedCentral

27.

Gurwitz D. Angiotensin receptor blockers as tentative SARS-CoV-2 therapeutics. Drug Dev Res. 2020. https://doi.org/10.1002/ddr.21656.CrossRefPubMedPubMedCentral

28.

Benicky J, Sánchez-Lemus E, Pavel J, Saavedra JM. Anti-inflammatory effects of angiotensin receptor blockers in the brain and the periphery. Cell Mol Neurobiol. 2009;29(6–7):781–92. https://doi.org/10.1007/s10571-009-9368-4.CrossRefPubMed

29.

Kristensen SL, Rørth R, Jhund PS, et al. Cardiovascular, mortality, and kidney outcomes with GLP-1 receptor agonists in patients with type 2 diabetes: a systematic review and meta-analysis of cardiovascular outcome trials. Lancet Diabetes Endocrinol. 2019;7(10):776–85. https://doi.org/10.1016/S2213-8587(19)30249-9.CrossRefPubMed

30.

Gerstein HC, Colhoun HM, Dagenais GR, et al. Dulaglutide and renal outcomes in type 2 diabetes: an exploratory analysis of the REWIND randomised, placebo-controlled trial. Lancet. 2019;394(10193):131–8. https://doi.org/10.1016/S0140-6736(19)31150-X.CrossRefPubMed

Title: ACE2 and SARS-CoV-2 Infection: Might GLP-1 Receptor Agonists Play a Role?
Authors: Vincenzo M. Monda
Francesca Porcellati
Felice Strollo
Sandro Gentile
Publication date: 01-09-2020
Publisher: Springer Healthcare
Keywords: SARS-CoV-2
Acute Respiratory Distress-Syndrome
COVID-19
Liraglutide
Incretin Mimetics
Incretin Mimetics
Published in: Diabetes Therapy / Issue 9/2020
Print ISSN: 1869-6953
Electronic ISSN: 1869-6961
DOI: https://doi.org/10.1007/s13300-020-00898-8

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