Diabetic individuals with COVID-19 exhibit reduced efficacy of gliptins in inhibiting dipeptidyl peptidase 4 (DPP4). A suggested explanation for increased COVID-19 susceptibility in patients with type 2 diabetes mellitus (T2DM)
Authors
Mora Rodríguez, José María; Sánchez Gómez, Belén; Bort Bueno, Alicia Carmen; Díaz Yuste, Alba; Ballesteros Gonzalez, Ruben; [et al.]Identifiers
Permanent link (URI): http://hdl.handle.net/10017/60635DOI: 10.1016/j.lfs.2023.122292
ISSN: 0024-3205
Date
2023-11-21Funders
Instituto de Salud Carlos III
Comunidad de Madrid
Universidad de Alcalá
Fundación Tatiana Pérez de Guzmán el Bueno
Bibliographic citation
Life Sciences, 2023, v. 336, n. 122292, p. 1-13
Keywords
DPP4
Gliptins
COVID-19
Type 2 diabetes
Enzymatic activity
Project
info:eu-repo/grantAgreement/ISCIII/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020 (ISCIII)/PI20%2F01327/ES/
info:eu-repo/grantAgreement/CM//REACT UE-CM2021-02/ES/
Document type
info:eu-repo/semantics/article
Version
info:eu-repo/semantics/publishedVersion
Rights
© 2023 The Authors
Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)
Access rights
info:eu-repo/semantics/openAccess
Abstract
Aims: Dipeptidyl peptidase 4 (DPP4) has been proposed as a coreceptor for SARS-CoV-2 cellular entry. Considering that type 2 diabetes mellitus (T2DM) has been identified as the most important risk factor for SARS-CoV-2, and that gliptins (DPP4 inhibitors) are a prescribed diabetic treatment, this study aims to unravel the impact of DPP4 in the intersection of T2DM/COVID-19. Materials and methods: We analyzed 189 serum human samples, divided into six clinical groups (controls, T2DM, T2DM + gliptins, COVID-19, COVID-19 + T2DM, and COVID-19 + T2DM + gliptins), measuring DPP4 protein concentration and activity by Western blot, ELISA, and commercial activity kits. The obtained results were verified in Huh-7 cellular models. Key findings: Both DPP4 concentration and activity were decreased in COVID-19 patients, and as in T2DM patients, compared to controls. Despite these lower levels, the ratio of DPP4 activity/concentration in COVID-19 sera was the highest (0.782 ± 0.289 ?U/ng vs. 0.547 ± 0.050 ?U/ng in controls, p < 0.0001), suggesting a compensating mechanism in these patients. Supernatants of Huh-7 cells incubated with COVID-19 serum showed a consistent and significantly lower DPP4 concentration and activity. Furthermore, COVID-19 + T2DM + gliptins patients showed a higher serum DPP4 concentration and activity than T2DM + gliptin subjects (p < 0.05), indicating that sera from COVID-19 convalescents interfere with gliptins. Significance: Either SARS-CoV-2 or some metabolites present in the sera of COVID-19-convalescent patients interact with soluble DPP4 or even gliptins themselves since the inhibitory effect of gliptins on DPP4 activity is being prevented. The interactions between DPP4, gliptins, and SARS-CoV-2 should be further elucidated to reveal the mechanism of action for these interesting observations.
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Diabetic_Mora_LifeSci_2023.pdf | 7.380Mb |
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