Dapagliflozin impedes endothelial cell senescence by activating the SIRT1 signaling pathway in type 2 diabetes

BackgroundSodium-glucose cotransporter 2 inhibitors (SGLT2i) clinically reduce atherosclerosis and lower blood pressure. However, their impact on endothelial dysfunction in type diabetes (T2D) remains unclear. In this study, we investigated the protective effect underlying mechanism of SGLT2 inhibitor dapagliflozin diabetes.MethodsVascular reactivity was measured to assess vasoprotective a mouse model high glucose (HG)-induced T2D. Pulse wave velocity quantify arterial stiffness. Protein expression assessed by western blotting immunofluorescence, oxidative stress evaluated using dihydroethidium, nitric oxide Griess reaction, cellular senescence based senescence-associated beta-galactosidase (SA‐β‐gal) activity markers. Furthermore, synthase (eNOS) acetylation status determined eNOS interactions with SIRT1 were coimmunoprecipitation assays.ResultsDapagliflozin protected against impaired endothelium-dependent vasorelaxation improved stiffness T2D; aortas had significantly reduced levels inflammatory factors. HG-induced increases activity, protein marker levels, vitro all ameliorated dapagliflozin. The decreases phosphorylation (NO) production senescent cells restored cells, expression. inhibition diminished antisenescence effects Coimmunoprecipitation showed that physically associated eNOS, suggesting are dependent activation.ConclusionThese findings indicate protects cell regulating signaling diabetic mice.