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)

• Published in: Life sciences (1973) 2024-01, Vol.336, p.122292-122292, Article 122292
• Main Authors: Mora-Rodríguez, José María, Sánchez, Belén G, Bort, Alicia, Díaz-Yuste, Alba, Ballester-González, Rubén, Arrieta, Francisco, Sebastián-Martín, Alba, Díaz-Laviada, Inés
• Format: Article
• Language: English
• ISSN: 0024-3205; 1879-0631
• DOI: 10.1016/j.lfs.2023.122292

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. 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. 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 μU/ng vs. 0.547 ± 0.050 μU/ng in controls, p