Generic placeholder image

Endocrine, Metabolic & Immune Disorders - Drug Targets

Editor-in-Chief

ISSN (Print): 1871-5303
ISSN (Online): 2212-3873

Review Article

Anti-Diabetic Drugs GLP-1 Agonists and DPP-4 Inhibitors may Represent Potential Therapeutic Approaches for COVID-19

Author(s): Aliah Alshanwani, Tarek Kashour* and Amira Badr

Volume 22, Issue 6, 2022

Published on: 24 January, 2022

Page: [571 - 578] Pages: 8

DOI: 10.2174/1871530321666210809153558

Price: $65

Abstract

The fast spread of coronavirus 2019 (COVID-19) calls for immediate action to counter the associated significant loss of human life and deep economic impact. Certain patient populations like those with obesity and diabetes are at higher risk for acquiring severe COVID-19 disease and have a higher risk of COVID-19 associated mortality. In the absence of an effective and safe vaccine, the only immediate promising approach is to repurpose an existing approved drug. Several drugs have been proposed and tested as adjunctive therapy for COVID-19. Among these drugs are the glucagon-like peptide-1 (GLP-1) 2 agonists and the dipeptidylpeptidase-4 (DPP-4) inhibitors. Beyond their glucose-lowering effects, these drugs have several pleiotropic protective properties, which include cardioprotective effects, anti-inflammatory and immunomodulatory activities, antifibrotic effects, antithrombotic effects, and vascular endothelial protective properties. This narrative review discusses these protective properties and addresses their scientific plausibility for their potential use as adjunctive therapy for COVID-19 disease.

Keywords: GLP-1, ACE-2, COVID-19, DPP-4, cardioprotective effects, immunomodulatory.

Graphical Abstract

[1]
Zhou, F; Yu, T; Du, R; Fan, G; Liu, Y; Liu, Z Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: A retrospective cohort study. Lancet Lond Engl., 2020, 395(10229), 1054-1062.
[2]
Rhee, S.Y.; Lee, J.; Nam, H.; Kyoung, D-S.; Shin, D.W.; Kim, D.J. Effects of a DPP-4 inhibitor and ras blockade on clinical outcomes of patients with diabetes and covid-19. Diabetes Metab. J., 2021, 45(2), 251-259.
[http://dx.doi.org/10.4093/dmj.2020.0206] [PMID: 33752274]
[3]
Wu, Z; McGoogan, JM Characteristics of and important lessons from the coronavirus disease 2019 (covid-19) outbreak in china: Summary of a report of 72 314 cases from the chinese center for disease control and prevention. JAMA, 2019, 323(13), 1239-1242.
[4]
Bode, B.; Garrett, V.; Messler, J.; McFarland, R.; Crowe, J.; Booth, R.; Klonoff, D.C. Glycemic characteristics and clinical outcomes of covid-19 patients hospitalized in the united states. J. Diabetes Sci. Technol., 2020, 14(4), 813-821.
[http://dx.doi.org/10.1177/1932296820924469] [PMID: 32389027]
[5]
Wang, Sufei Fasting blood glucose at admission is an independent predictor for 28-day mortality in1 patients with COVID-19 without previous diagnosis of diabetes: a multi-centre retrospective study 2. Diabetologia, 2020.
[http://dx.doi.org/10.1007/s00125-020-05209-1]
[6]
Hodgson, K.; Morris, J.; Bridson, T.; Govan, B.; Rush, C.; Ketheesan, N. Immunological mechanisms contributing to the double burden of diabetes and intracellular bacterial infections. Immunology, 2015, 144(2), 171-185.
[http://dx.doi.org/10.1111/imm.12394] [PMID: 25262977]
[7]
Guo, Y-R; Cao, Q-D; Hong, Z-S; Tan, Y-Y; Chen, S-D; Jin, H-J The origin, transmission and clinical therapies on coronavirus disease 2019 (COVID-19) outbreak - an update on the status. Mil. Med. Res., 2019, 7(1), 11.
[8]
Pinheiro, M.M.; Fabbri, A.; Infante, M. Cytokine storm modulation in COVID-19: A proposed role for vitamin D and DPP-4 inhibitor combination therapy (VIDPP-4i). Immunotherapy, 2021, 13(9), 753-765.
[http://dx.doi.org/10.2217/imt-2020-0349] [PMID: 33906375]
[9]
Varga, Z; Flammer, AJ; Steiger, P; Haberecker, M; Andermatt, R; Zinkernagel, AS Endothelial cell infection and endotheliitis in COVID-19. Lancet Lond Engl., 2020, 395(10234), 1417-1418.
[10]
Asselah, T.; Durantel, D.; Pasmant, E.; Lau, G.; Schinazi, R.F. COVID-19: Discovery, diagnostics and drug development. J. Hepatol., 2021, 74(1), 168-184.
[http://dx.doi.org/10.1016/j.jhep.2020.09.031] [PMID: 33038433]
[11]
Singh, H.; Kaur, H.; Singh, K.; Sen, C.K. Cutaneous manifestations of COVID-19: a systematic review. Adv. Wound Care (New Rochelle), 2021, 10(2), 51-80.
[http://dx.doi.org/10.1089/wound.2020.1309] [PMID: 33035150]
[12]
Drucker, D.J.; Nauck, M.A. The incretin system: glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors in type 2 diabetes. Lancet, 2006, 368(9548), 1696-1705.
[http://dx.doi.org/10.1016/S0140-6736(06)69705-5] [PMID: 17098089]
[13]
Du, H.; Wang, D.W.; Chen, C. The potential effects of DPP-4 inhibitors on cardiovascular system in COVID-19 patients. J. Cell. Mol. Med., 2020, 24(18), 10274-10278.
[http://dx.doi.org/10.1111/jcmm.15674] [PMID: 32713161]
[14]
Israelsen, S.B.; Pottegård, A.; Sandholdt, H.; Madsbad, S.; Thomsen, R.W.; Benfield, T. Comparable COVID-19 outcomes with current use of GLP-1 receptor agonists, DPP-4 inhibitors or SGLT-2 inhibitors among patients with diabetes who tested positive for SARS-CoV-2. Diabetes Obes. Metab., 2021, 23(6), 1397-1401.
[http://dx.doi.org/10.1111/dom.14329] [PMID: 33502076]
[15]
Chen, Y.; Yang, D.; Yang, C.; Zheng, L.; Huang, K. Response to comment on Chen et al. Clinical characteristics and outcomes of patients with diabetes and covid-19 in association with glucose-lowering medication. diabetes care 2020;43:1399-1407. Diabetes Care, 2020, 43(10), e165-e166.
[http://dx.doi.org/10.2337/dci20-0035] [PMID: 32958627]
[16]
Solerte, S.B.; D’Addio, F.; Trevisan, R.; Lovati, E.; Rossi, A.; Pastore, I.; Dell’Acqua, M.; Ippolito, E.; Scaranna, C.; Bellante, R.; Galliani, S.; Dodesini, A.R.; Lepore, G.; Geni, F.; Fiorina, R.M.; Catena, E.; Corsico, A.; Colombo, R.; Mirani, M.; De Riva, C.; Oleandri, S.E.; Abdi, R.; Bonventre, J.V.; Rusconi, S.; Folli, F.; Di Sabatino, A.; Zuccotti, G.; Galli, M.; Fiorina, P. Sitagliptin treatment at the time of hospitalization was associated with reduced mortality in patients with type 2 diabetes and covid-19: A multicenter, case-control, retrospective, observational study. Diabetes Care, 2020, 43(12), 2999-3006.
[http://dx.doi.org/10.2337/dc20-1521] [PMID: 32994187]
[17]
Noh, Y.; Oh, I-S.; Jeong, H.E.; Filion, K.B.; Yu, O.H.Y.; Shin, J-Y. association Between DPP-4 inhibitors and covid-19-related outcomes among patients with type 2 diabetes. Diabetes Care, 2021, 44(4), e64-e66.
[http://dx.doi.org/10.2337/dc20-1824] [PMID: 33547204]
[18]
Mirani, M.; Favacchio, G.; Carrone, F.; Betella, N.; Biamonte, E.; Morenghi, E.; Mazziotti, G.; Lania, A.G. Impact of comorbidities and glycemia at admission and dipeptidyl peptidase 4 inhibitors in patients with type 2 diabetes with covid-19: A case series from an academic hospital in Lombardy, Italy. Diabetes Care, 2020, 43(12), 3042-3049.
[http://dx.doi.org/10.2337/dc20-1340] [PMID: 33023989]
[19]
Alavi, SE; Cabot, PJ; Moyle, PM Glucagon-like peptide-1 receptor agonists and strategies to improve their efficiency. Mol Pharm., 2019, 16(6), 2278-2295.
[http://dx.doi.org/10.1021/acs.molpharmaceut.9b00308]
[20]
Meloni, A.R.; DeYoung, M.B.; Lowe, C.; Parkes, D.G. GLP-1 receptor activated insulin secretion from pancreatic β-cells: Mechanism and glucose dependence. Diabetes Obes. Metab., 2013, 15(1), 15-27.
[http://dx.doi.org/10.1111/j.1463-1326.2012.01663.x] [PMID: 22776039]
[21]
Mirabelli, M; Chiefari, E; Caroleo, P; Arcidiacono, B; Corigliano, DM; Giuliano, S. Long-term effectiveness of liraglutide for weight management and glycemic control in type 2 diabetes. Int J Environ Res Public Health, 2019, 17(1), 207.
[22]
Deacon, C.F. Physiology and pharmacology of dpp-4 in glucose homeostasis and the treatment of type 2 diabetes. Front. Endocrinol. (Lausanne), 2019, 10, 80.
[http://dx.doi.org/10.3389/fendo.2019.00080] [PMID: 30828317]
[23]
Ohnuma, K.; Dang, N.H.; Morimoto, C. Revisiting an old acquaintance: CD26 and its molecular mechanisms in T cell function. Trends Immunol., 2008, 29(6), 295-301.
[http://dx.doi.org/10.1016/j.it.2008.02.010] [PMID: 18456553]
[24]
Sun, B.; Huang, S.; Zhou, J. Perspectives of antidiabetic drugs in diabetes with coronavirus infections. Front Pharmacol, 2021, 11, 592439. Available from: https://www.frontiersin.org/articles/10.3389/fphar.2020.592439/full [Cited 2021 May 5]
[25]
Fandiño, J.; Vaz, A.A.; Toba, L.; Romaní-Pérez, M.; González-Matías, L.; Mallo, F.; Diz-Chaves, Y. 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.
[http://dx.doi.org/10.1155/2018/6920620] [PMID: 30627159]
[26]
Lee, Y-S.; Jun, H-S. Anti-inflammatory effects of glp-1-based therapies beyond glucose control. Mediators Inflamm., 2016, 2016, 3094642.
[http://dx.doi.org/10.1155/2016/3094642] [PMID: 27110066]
[27]
Nauck, M.A.; Meier, J.J.; Cavender, M.A.; Abd El Aziz, M.; Drucker, D.J. Cardiovascular actions and clinical outcomes with glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors. Circulation, 2017, 136(9), 849-870.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.117.028136] [PMID: 28847797]
[28]
Zhu, T.; Wu, X-L.; Zhang, W.; Xiao, M. Glucagon like peptide-1 (glp-1) modulates ova-induced airway inflammation and mucus secretion involving a protein kinase a (pka)-dependent nuclear factor-κb (nf-κb) signaling pathway in mice. Int. J. Mol. Sci., 2015, 16(9), 20195-20211.
[http://dx.doi.org/10.3390/ijms160920195] [PMID: 26343632]
[29]
Pedersen, SF; Ho, Y-C SARS-CoV-2: A storm is raging. J Clin Invest., 2020, 130(5), 2202-2205.
[30]
Solerte, S.B.; Di Sabatino, A.; Galli, M.; Fiorina, P. Dipeptidyl peptidase-4 (DPP4) inhibition in COVID-19. Acta Diabetol., 2020, 57(7), 779-783.
[http://dx.doi.org/10.1007/s00592-020-01539-z] [PMID: 32506195]
[31]
Higashijima, Y.; Tanaka, T.; Yamaguchi, J.; Tanaka, S.; Nangaku, M. Anti-inflammatory role of DPP-4 inhibitors in a nondiabetic model of glomerular injury. Am. J. Physiol. Renal Physiol., 2015, 308(8), F878-F887.
[http://dx.doi.org/10.1152/ajprenal.00590.2014] [PMID: 25656369]
[32]
Lee, J.M.; Yoo, I.K.; Lee, J.M.; Kim, S.H.; Choi, H.S.; Kim, E.S.; Keum, B.; Seo, Y.S.; Jeen, Y.T.; Chun, H.J.; Lee, H.S.; Um, S.H.; Kim, C.D. Dipeptidyl-peptidase-4 (DPP-4) inhibitor ameliorates 5-flurouracil induced intestinal mucositis. BMC Cancer, 2019, 19(1), 1016.
[http://dx.doi.org/10.1186/s12885-019-6231-y] [PMID: 31664952]
[33]
Wiciński, M.; Wódkiewicz, E.; Słupski, M.; Walczak, M.; Socha, M.; Malinowski, B.; Pawlak-Osińska, K. Neuroprotective activity of sitagliptin via reduction of neuroinflammation beyond the incretin effect: focus on Alzheimer’s disease. BioMed Res. Int., 2018, 2018, 6091014.
[http://dx.doi.org/10.1155/2018/6091014] [PMID: 30186862]
[34]
Alonso, N.; Julián, M.T.; Puig-Domingo, M.; Vives-Pi, M. Incretin hormones as immunomodulators of atherosclerosis. Front. Endocrinol. (Lausanne), 2012, 3, 112.
[http://dx.doi.org/10.3389/fendo.2012.00112] [PMID: 22973260]
[35]
Jojima, T.; Tomotsune, T.; Iijima, T.; Akimoto, K.; Suzuki, K.; Aso, Y. Empagliflozin (an SGLT2 inhibitor), alone or in combination with linagliptin (a DPP-4 inhibitor), prevents steatohepatitis in a novel mouse model of non-alcoholic steatohepatitis and diabetes. Diabetol. Metab. Syndr., 2016, 8, 45.
[http://dx.doi.org/10.1186/s13098-016-0169-x] [PMID: 27462372]
[36]
Kawasaki, T; Chen, W; Htwe, YM; Tatsumi, K; Dudek, SM DPP4 inhibition by sitagliptin attenuates LPS-induced lung injury in mice. Am J Physiol Lung Cell Mol Physiol., 2018, 315(5), L834-L845.
[37]
Sa-Nguanmoo, P.; Tanajak, P.; Kerdphoo, S.; Jaiwongkam, T.; Pratchayasakul, W.; Chattipakorn, N.; Chattipakorn, S.C. SGLT2-inhibitor and DPP-4 inhibitor improve brain function via attenuating mitochondrial dysfunction, insulin resistance, inflammation, and apoptosis in HFD-induced obese rats. Toxicol. Appl. Pharmacol., 2017, 333(333), 43-50.
[http://dx.doi.org/10.1016/j.taap.2017.08.005] [PMID: 28807765]
[38]
Yaribeygi, H.; Maleki, M.; Sathyapalan, T.; Jamialahmadi, T.; Sahebkar, A. Anti-inflammatory potentials of incretin-based therapies used in the management of diabetes. Life Sci., 2020, 241, 117152.
[http://dx.doi.org/10.1016/j.lfs.2019.117152] [PMID: 31837333]
[39]
Tremblay, A.J.; Lamarche, B.; Deacon, C.F.; Weisnagel, S.J.; Couture, P. Effects of sitagliptin therapy on markers of low-grade inflammation and cell adhesion molecules in patients with type 2 diabetes. Metabolism, 2014, 63(9), 1141-1148.
[http://dx.doi.org/10.1016/j.metabol.2014.06.004] [PMID: 25034387]
[40]
Zabetakis, I.; Lordan, R.; Norton, C.; Tsoupras, A. COVID-19: The inflammation link and the role of nutrition in potential mitigation. Nutrients, 2020, 12(5), 1466 . https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7284818/ [Cited 2020 Oct 13]
[41]
Kokic Males, V. Letter to the editor in response to the article “COVID-19 and diabetes: Can DPP4 inhibition play a role?”. Diabetes Res. Clin. Pract., 2020, 163, 108163.
[http://dx.doi.org/10.1016/j.diabres.2020.108163] [PMID: 32333972]
[42]
Dalan, R. Is DPP4 inhibition a comrade or adversary in COVID-19 infection. Diabetes Res. Clin. Pract., 2020, 164, 108216.
[http://dx.doi.org/10.1016/j.diabres.2020.108216] [PMID: 32416120]
[43]
Roussel, R.; Darmon, P.; Pichelin, M.; Goronflot, T.; Abouleka, Y.; Ait Bachir, L.; Allix, I.; Ancelle, D.; Barraud, S.; Bordier, L.; Carlier, A.; Chevalier, N.; Coffin-Boutreux, C.; Cosson, E.; Dorange, A.; Dupuy, O.; Fontaine, P.; Fremy, B.; Galtier, F.; Germain, N.; Guedj, A.M.; Larger, E.; Laugier-Robiolle, S.; Laviolle, B.; Ludwig, L.; Monier, A.; Montanier, N.; Moulin, P.; Moura, I.; Prevost, G.; Reznik, Y.; Sabbah, N.; Saulnier, P.J.; Serusclat, P.; Vatier, C.; Wargny, M.; Hadjadj, S.; Gourdy, P.; Cariou, B. Use of dipeptidyl peptidase-4 inhibitors and prognosis of COVID-19 in hospitalized patients with type 2 diabetes: A propensity score analysis from the CORONADO study. Diabetes Obes. Metab., 2021, 23(5), 1162-1172.
[http://dx.doi.org/10.1111/dom.14324] [PMID: 33528920]
[44]
Romaní-Pérez, M.; Outeiriño-Iglesias, V.; Moya, C.M.; Santisteban, P.; González-Matías, L.C.; Vigo, E.; Mallo, F. 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), 3559-3569.
[http://dx.doi.org/10.1210/en.2014-1685] [PMID: 26196539]
[45]
Rao, S.; Lau, A.; So, H-C. Exploring diseases/traits and blood proteins causally related to expression of ace2, the putative receptor of sars-cov-2: A mendelian randomization analysis highlights tentative relevance of diabetes-related traits. Diabetes Care, 2020, 43(7), 1416-1426.
[http://dx.doi.org/10.2337/dc20-0643] [PMID: 32430459]
[46]
Roca-Ho, H.; Riera, M.; Palau, V.; Pascual, J.; Soler, M.J. Characterization of ace and ace2 expression within different organs of the nod mouse. Int. J. Mol. Sci., 2017, 18(3), E563.
[http://dx.doi.org/10.3390/ijms18030563] [PMID: 28273875]
[47]
Wösten-van Asperen, R.M.; Bos, A.P.; Bem, R.A.; Dierdorp, B.S.; Dekker, T.; van Goor, H.; Kamilic, J.; van der Loos, C.M.; van den Berg, E.; Bruijn, M.; van Woensel, J.B.; Lutter, R. Imbalance between pulmonary angiotensin-converting enzyme and angiotensin-converting enzyme 2 activity in acute respiratory distress syndrome. Pediatr. Crit. Care Med., 2013, 14(9), e438-e441.
[http://dx.doi.org/10.1097/PCC.0b013e3182a55735] [PMID: 24226567]
[48]
Zhang, L-H.; Pang, X-F.; Bai, F.; Wang, N-P.; Shah, A.I.; McKallip, R.J.; Li, X.W.; Wang, X.; Zhao, Z.Q. Preservation of glucagon-like peptide-1 level attenuates angiotensin ii-induced tissue fibrosis by altering at1/at 2 receptor expression and angiotensin-converting enzyme 2 activity in rat heart. Cardiovasc. Drugs Ther., 2015, 29(3), 243-255.
[http://dx.doi.org/10.1007/s10557-015-6592-7] [PMID: 25994830]
[49]
Fang, C.; Stavrou, E.; Schmaier, A.A.; Grobe, N.; Morris, M.; Chen, A.; Nieman, M.T.; Adams, G.N.; LaRusch, G.; Zhou, Y.; Bilodeau, M.L.; Mahdi, F.; Warnock, M.; Schmaier, A.H. 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), 3023-3032.
[http://dx.doi.org/10.1182/blood-2012-09-459156] [PMID: 23386129]
[50]
Benigni, A.; Cassis, P.; Remuzzi, G. Angiotensin II revisited: New roles in inflammation, immunology and aging. EMBO Mol. Med., 2010, 2(7), 247-257.
[http://dx.doi.org/10.1002/emmm.201000080] [PMID: 20597104]
[51]
Vaduganathan, M; Vardeny, O; Michel, T; McMurray, JJV; Pfeffer, MA; Solomon, SD Renin-Angiotensin-Aldosterone system inhibitors in patients with covid-19. N Engl J Med., 2020, 382(17), 1653-1659.
[52]
Kuba, K.; Imai, Y.; Rao, S.; Gao, H.; Guo, F.; Guan, B.; Huan, Y.; Yang, P.; Zhang, Y.; Deng, W.; Bao, L.; Zhang, B.; Liu, G.; Wang, Z.; Chappell, M.; Liu, Y.; Zheng, D.; Leibbrandt, A.; Wada, T.; Slutsky, A.S.; Liu, D.; Qin, C.; Jiang, C.; Penninger, J.M. A crucial role of angiotensin converting enzyme 2 (ACE2) in SARS coronavirus-induced lung injury. Nat. Med., 2005, 11(8), 875-879.
[http://dx.doi.org/10.1038/nm1267] [PMID: 16007097]
[53]
Akhtar, S.; Benter, I.F.; Danjuma, M.I.; Doi, S.A.R.; Hasan, S.S.; Habib, A.M. Pharmacotherapy in COVID-19 patients: a review of ACE2-raising drugs and their clinical safety. J. Drug Target., 2020, 28(7-8), 683-699.
[http://dx.doi.org/10.1080/1061186X.2020.1797754] [PMID: 32700580]
[54]
Yang, M.; Ma, X.; Xuan, X.; Deng, H.; Chen, Q.; Yuan, L. Liraglutide attenuates non-alcoholic fatty liver disease in mice by regulating the local renin-angiotensin system. Front. Pharmacol., 2020, 11, 432.
[http://dx.doi.org/10.3389/fphar.2020.00432] [PMID: 32322207]
[55]
Ceriello, A.; Standl, E.; Catrinoiu, D.; Itzhak, B.; Lalic, N.M.; Rahelic, D.; Schnell, O.; Škrha, J.; Valensi, P. Issues of cardiovascular risk management in people with diabetes in the COVID-19 era. Diabetes Care, 2020, 43(7), 1427-1432.
[http://dx.doi.org/10.2337/dc20-0941] [PMID: 32409501]
[56]
Zhou, F.; Zhang, Y.; Chen, J.; Hu, X.; Xu, Y. Liraglutide attenuates lipopolysaccharide-induced acute lung injury in mice. Eur. J. Pharmacol., 2016, 791, 735-740.
[http://dx.doi.org/10.1016/j.ejphar.2016.10.016] [PMID: 27756605]
[57]
Hamming, I.; Timens, W.; Bulthuis, M.L.C.; Lely, A.T.; Navis, G.; van Goor, H. Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis. J. Pathol., 2004, 203(2), 631-637.
[http://dx.doi.org/10.1002/path.1570] [PMID: 15141377]
[58]
Batlle, D; Wysocki, J; Satchell, K. Soluble angiotensin-converting enzyme 2: A potential approach for coronavirus infection therapy. Clin. Sci. Lond Engl., 1979, 134(5), 543-545.
[59]
Feng, Y; Wang, L; Ma, X; Yang, X; Don, O; Chen, X Effect of hCMSCs and liraglutide combination in ALI through cAMP/PKAc/β-catenin signaling pathway. Stem Cell Res. Ther., 2020, 11(1), 2.
[60]
Xu, J.; Wei, G.; Wang, J.; Zhu, J.; Yu, M.; Zeng, X.; Wang, H.; Xie, W.; Kong, H. Glucagon-like peptide-1 receptor activation alleviates lipopolysaccharide-induced acute lung injury in mice via maintenance of endothelial barrier function. Lab. Invest., 2019, 99(4), 577-587.
[http://dx.doi.org/10.1038/s41374-018-0170-0] [PMID: 30659271]
[61]
van den Berg, D.F.; Te Velde, A.A. Severe COVID-19: NLRP3 inflammasome dysregulated. Front. Immunol., 2020, 11, 1580.
[http://dx.doi.org/10.3389/fimmu.2020.01580] [PMID: 32670297]
[62]
Yap, JKY; Moriyama, M; Iwasaki, A Inflammasomes and pyroptosis as therapeutic targets for COVID-19. J. Immunol. Baltim Md, 1950, 205(2), 307-312.
[63]
Bloodworth, M.H.; Rusznak, M.; Pfister, C.C.; Zhang, J.; Bastarache, L.; Calvillo, S.A.; Chappell, J.D.; Boyd, K.L.; Toki, S.; Newcomb, D.C.; Stier, M.T.; Zhou, W.; Goleniewska, K.; Moore, M.L.; Hartert, T.V.; Niswender, K.D.; Peebles, R.S., Jr Glucagon-like peptide 1 receptor signaling attenuates respiratory syncytial virus-induced type 2 responses and immunopathology. J. Allergy Clin. Immunol., 2018, 142(2), 683-687.e12.
[http://dx.doi.org/10.1016/j.jaci.2018.01.053] [PMID: 29678751]
[64]
Nader, M.A. Inhibition of airway inflammation and remodeling by sitagliptin in murine chronic asthma. Int. Immunopharmacol., 2015, 29(2), 761-769.
[http://dx.doi.org/10.1016/j.intimp.2015.08.043] [PMID: 26362207]
[65]
Helal, M.G.; Megahed, N.A.; Abd Elhameed, A.G. Saxagliptin mitigates airway inflammation in a mouse model of acute asthma via modulation of NF-kB and TLR4. Life Sci., 2019, 239, 117017.
[http://dx.doi.org/10.1016/j.lfs.2019.117017] [PMID: 31678284]
[66]
Guo, K; Jin, F. Dipeptidyl peptidase-4 (DPP-4) inhibitor saxagliptin alleviates lipopolysaccharide-induced acute lung injury via regulating the Nrf-2/HO-1 and NF- κ B pathways. J. Invest. Surg., 2019, 1-8.
[67]
Soare, A.; Györfi, H.A.; Matei, A.E.; Dees, C.; Rauber, S.; Wohlfahrt, T.; Chen, C.W.; Ludolph, I.; Horch, R.E.; Bäuerle, T.; von Hörsten, S.; Mihai, C.; Distler, O.; Ramming, A.; Schett, G.; Distler, J.H.W. Dipeptidylpeptidase 4 as a marker of activated fibroblasts and a potential target for the treatment of fibrosis in systemic sclerosis. Arthritis Rheumatol., 2020, 72(1), 137-149.
[http://dx.doi.org/10.1002/art.41058] [PMID: 31350829]
[68]
Strollo, R.; Pozzilli, P. DPP4 inhibition: Preventing SARS-CoV-2 infection and/or progression of COVID-19? Diabetes Metab. Res. Rev., 2020, 36(8), e3330.
[http://dx.doi.org/10.1002/dmrr.3330] [PMID: 32336007]
[69]
Giacco, F.; Du, X.; Carratú, A.; Gerfen, G.J.; D’Apolito, M.; Giardino, I.; Rasola, A.; Marin, O.; Divakaruni, A.S.; Murphy, A.N.; Shah, M.S.; Brownlee, M. GLP-1 cleavage product reverses persistent ros generation after transient hyperglycemia by disrupting an ros-generating feedback loop. Diabetes, 2015, 64(9), 3273-3284.
[http://dx.doi.org/10.2337/db15-0084] [PMID: 26294429]
[70]
Ussher, J.R.; Drucker, D.J. Cardiovascular biology of the incretin system. Endocr. Rev., 2012, 33(2), 187-215.
[http://dx.doi.org/10.1210/er.2011-1052] [PMID: 22323472]
[71]
Cameron-Vendrig, A.; Reheman, A.; Siraj, M.A.; Xu, X.R.; Wang, Y.; Lei, X.; Afroze, T.; Shikatani, E.; El-Mounayri, O.; Noyan, H.; Weissleder, R.; Ni, H.; Husain, M. Glucagon-like peptide 1 receptor activation attenuates platelet aggregation and thrombosis. Diabetes, 2016, 65(6), 1714-1723.
[http://dx.doi.org/10.2337/db15-1141] [PMID: 26936963]
[72]
Hausenloy, D.J.; Whittington, H.J.; Wynne, A.M.; Begum, S.S.; Theodorou, L.; Riksen, N.; Mocanu, M.M.; Yellon, D.M. Dipeptidyl peptidase-4 inhibitors and GLP-1 reduce myocardial infarct size in a glucose-dependent manner. Cardiovasc. Diabetol., 2013, 12, 154.
[http://dx.doi.org/10.1186/1475-2840-12-154] [PMID: 24148218]
[73]
Hattori, Y.; Jojima, T.; Tomizawa, A.; Satoh, H.; Hattori, S.; Kasai, K.; Hayashi, T. A glucagon-like peptide-1 (GLP-1) analogue, liraglutide, upregulates nitric oxide production and exerts anti-inflammatory action in endothelial cells. Diabetologia, 2010, 53(10), 2256-2263.
[http://dx.doi.org/10.1007/s00125-010-1831-8] [PMID: 20593161]
[74]
Gaspari, T.; Liu, H.; Welungoda, I.; Hu, Y.; Widdop, R.E.; Knudsen, L.B.; Simpson, R.W.; Dear, A.E. A GLP-1 receptor agonist liraglutide inhibits endothelial cell dysfunction and vascular adhesion molecule expression in an ApoE-/- mouse model. Diab. Vasc. Dis. Res., 2011, 8(2), 117-124.
[http://dx.doi.org/10.1177/1479164111404257] [PMID: 21562063]
[75]
Steven, S.; Hausding, M.; Kröller-Schön, S.; Mader, M.; Mikhed, Y.; Stamm, P.; Zinßius, E.; Pfeffer, A.; Welschof, P.; Agdauletova, S.; Sudowe, S.; Li, H.; Oelze, M.; Schulz, E.; Klein, T.; Münzel, T.; Daiber, A. Gliptin and GLP-1 analog treatment improves survival and vascular inflammation/dysfunction in animals with lipopolysaccharide-induced endotoxemia. Basic Res. Cardiol., 2015, 110(2), 6.
[http://dx.doi.org/10.1007/s00395-015-0465-x] [PMID: 25600227]
[76]
Jia, G.; Aroor, A.R.; Sowers, J.R. Glucagon-like peptide 1 receptor activation and platelet function: beyond glycemic control. Diabetes, 2016, 65(6), 1487-1489.
[http://dx.doi.org/10.2337/dbi16-0014] [PMID: 27222394]
[77]
Ussher, J.R.; Drucker, D.J. Cardiovascular actions of incretin-based therapies. Circ. Res., 2014, 114(11), 1788-1803.
[http://dx.doi.org/10.1161/CIRCRESAHA.114.301958] [PMID: 24855202]
[78]
Kang, Y.; Chen, T.; Mui, D.; Ferrari, V.; Jagasia, D.; Scherrer-Crosbie, M.; Chen, Y.; Han, Y. Cardiovascular manifestations and treatment considerations in COVID-19. Heart, 2020, 106(15), 1132-1141.
[http://dx.doi.org/10.1136/heartjnl-2020-317056] [PMID: 32354800]
[79]
Sun, F.; Wu, S.; Wang, J.; Guo, S.; Chai, S.; Yang, Z.; Li, L.; Zhang, Y.; Ji, L.; Zhan, S. Effect of glucagon-like peptide-1 receptor agonists on lipid profiles among type 2 diabetes: a systematic review and network meta-analysis. Clin. Ther., 2015, 37(1), 225-241.e8.
[http://dx.doi.org/10.1016/j.clinthera.2014.11.008] [PMID: 25554560]
[80]
Farr, S.; Adeli, K. Incretin-based therapies for treatment of postprandial dyslipidemia in insulin-resistant states. Curr. Opin. Lipidol., 2012, 23(1), 56-61.
[http://dx.doi.org/10.1097/MOL.0b013e32834d68f0] [PMID: 22123671]
[81]
Rowlands, J.; Heng, J.; Newsholme, P.; Carlessi, R. Pleiotropic effects of glp-1 and analogs on cell signaling, metabolism, and function. Front. Endocrinol. (Lausanne), 2018, 9, 672.
[http://dx.doi.org/10.3389/fendo.2018.00672] [PMID: 30532733]
[82]
Irace, C.; De Luca, S.; Shehaj, E.; Carallo, C.; Loprete, A.; Scavelli, F.; Gnasso, A. Exenatide improves endothelial function assessed by flow mediated dilation technique in subjects with type 2 diabetes: results from an observational research. Diab. Vasc. Dis. Res., 2013, 10(1), 72-77.
[http://dx.doi.org/10.1177/1479164112449562] [PMID: 22732108]
[83]
Chinda, K.; Chattipakorn, S.; Chattipakorn, N. Cardioprotective effects of incretin during ischaemia-reperfusion. Diab. Vasc. Dis. Res., 2012, 9(4), 256-269.
[http://dx.doi.org/10.1177/1479164112440816] [PMID: 22496404]
[84]
Mulvihill, E.E.; Drucker, D.J. Pharmacology, physiology, and mechanisms of action of dipeptidyl peptidase-4 inhibitors. Endocr. Rev., 2014, 35(6), 992-1019.
[http://dx.doi.org/10.1210/er.2014-1035] [PMID: 25216328]
[85]
Long, B.; Brady, W.J.; Koyfman, A.; Gottlieb, M. Cardiovascular complications in COVID-19. Am. J. Emerg. Med., 2020, 38(7), 1504-1507.
[http://dx.doi.org/10.1016/j.ajem.2020.04.048] [PMID: 32317203]
[86]
Zheng, Y-Y.; Ma, Y-T.; Zhang, J-Y.; Xie, X. COVID-19 and the cardiovascular system. Nat. Rev. Cardiol., 2020, 17(5), 259-260.
[http://dx.doi.org/10.1038/s41569-020-0360-5] [PMID: 32139904]
[87]
Nishiga, M.; Wang, D.W.; Han, Y.; Lewis, D.B.; Wu, J.C. COVID-19 and cardiovascular disease: from basic mechanisms to clinical perspectives. Nat. Rev. Cardiol., 2020, 17(9), 543-558.
[http://dx.doi.org/10.1038/s41569-020-0413-9] [PMID: 32690910]
[88]
South, AM; Diz, DI; Chappell, MC COVID-19, ACE2, and the cardiovascular consequences. Am J Physiol Heart Circ Physiol., 2020, 318(5), H1084-H1090.
[89]
Madjid, M; Safavi-Naeini, P; Solomon, SD; Vardeny, O. Potential effects of coronaviruses on the cardiovascular system: A review. JAMA Cardiol., 2020, 5(7), 831-840.
[http://dx.doi.org/10.1001/jamacardio.2020.1286]
[90]
Monteil, V.; Kwon, H.; Prado, P.; Hagelkrüys, A.; Wimmer, R.A.; Stahl, M.; Leopoldi, A.; Garreta, E.; Hurtado Del Pozo, C.; Prosper, F.; Romero, J.P.; Wirnsberger, G.; Zhang, H.; Slutsky, A.S.; Conder, R.; Montserrat, N.; Mirazimi, A.; Penninger, J.M. Inhibition of SARS-CoV2 infections in engineered human tissues using clinical-grade soluble human ACE2. Cell, 2020, 181(4), 905-913.e7.
[http://dx.doi.org/10.1016/j.cell.2020.04.004] [PMID: 32333836]
[91]
Guzik, TJ; Mohiddin, SA; Dimarco, A; Patel, V; Savvatis, K; Marelli-Berg, FM COVID-19 and the cardiovascular system: Implications for risk assessment, diagnosis, and treatment options. Cardiovasc Res., 2020, 116(10), 1666-1687.

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy