Pharmacological analysis of Empagliflozin: Acting through the CaMKII pathway in type 2 diabetes and acute cardiovascular events

BACKGROUND: Type 2 diabetes mellitus is a high-risk factor for acute cardiovascular events. Some reports show that Empagliflozin has a protective effect on cardiovascular events and diabetes mellitus, and Empagliflozin can act on the CaMKII pathway. However, the specific gene of action is not precise. Therefore, this study investigated the target genes of Empagliflozin by integrated gene analysis and molecular docking method to provide a theoretical basis for further elucidating the mechanism of action of Empagliflozin. METHOD: In this study, we obtained 12 datasets from GEO, divided into experimental and validation groups, with a total of 376 samples. We then integrated CaMKII pathway-related genes from OMIM, NCBI, and genecards databases. We then intersected them with the differential genes we obtained to obtain 5 common genes and performed functional enrichment analysis. We then performed group comparisons in the validation set, and we obtained 2 clinically significant genes. Then we performed group comparison in the validation set, and we obtained 2 clinically significant genes, followed by molecular docking analysis with pymol, autodock software. We obtained molecular docking models for the 2 genes. CONCLUSION: In this study, we obtained CaMK2G and PPP1CA, genes associated with the CaMKII pathway and type 2 diabetes and acute cardiovascular events, by integrative gene analysis and validated their expression in the relevant dataset. We also derived that Empagliflozin acts on amino acid TRP-125 of CaMK2G gene and GLN-249 ASP-210 ASP-208 of PPP1CA through CaMKII pathway, thus acting on type 2 diabetes and acute cardiovascular events by molecular docking technique.