{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T03:09:04Z","timestamp":1787972944597,"version":"build-2784847793"},"reference-count":48,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2022,5,9]],"date-time":"2022-05-09T00:00:00Z","timestamp":1652054400000},"content-version":"vor","delay-in-days":128,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81770305"],"award-info":[{"award-number":["81770305"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82170420"],"award-info":[{"award-number":["82170420"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Oxidative Medicine and Cellular Longevity"],"published-print":{"date-parts":[[2022,1]]},"abstract":"<jats:p>Diabetic cardiomyopathy (DCM) is considered to be a critical contributor to the development of heart failure. Empagliflozin (EMPA), a sodium\u2010glucose cotransporter 2 inhibitor, has been shown to prevent cardiovascular events and reduce the incidence of heart failure in randomized clinical trials. However, the mechanism of how EMPA prevents DCM is poorly understood. To study the potential mechanisms involved in the therapeutic effects of EMPA, we assessed the protective effects of EMPA on myocardial injury in type 2 diabetic <jats:italic>db\/db<\/jats:italic> mice and H9C2 cardiomyocytes. 9\u201310\u2010week\u2010old male <jats:italic>db\/db<\/jats:italic> mice were treated with EMPA (10\u2009mg\/kg) via oral gavage daily for 20 weeks. Afterward, cardiac function of treated mice was evaluated by echocardiography, and pathological changes in heart tissues were determined by histopathological examination and western blot assay. EMPA markedly reduced blood glucose levels, improved insulin tolerance, and enhanced insulin sensitivity of <jats:italic>db\/db<\/jats:italic> mice. In addition, EMPA significantly prevented cardiac dysfunction, inhibited cardiac hypertrophy and fibrosis, and reduced glycogen deposition in heart tissues. Furthermore, EMPA improved diabetes\u2010induced oxidative stress and mitochondrial dysfunction in both heart tissues of <jats:italic>db\/db<\/jats:italic> mice and palmitate exposed H9C2 cells. EMPA significantly increased the expression of nuclear factor erythroid 2\u2010related factor 2 (Nrf2) and its downstream genetic targets in cardiac tissue of type 2 diabetic <jats:italic>db\/db<\/jats:italic> mice and H9C2 cells. EMPA also downregulated the expression of mitochondrial fission\u2010related proteins and upregulated the expression of mitochondrial fusion\u2010related proteins. Collectively, these findings indicate that EMPA may prevent DCM via attenuating oxidative stress and improving mitochondrial function in heart tissue.<\/jats:p>","DOI":"10.1155\/2022\/1122494","type":"journal-article","created":{"date-parts":[[2022,5,9]],"date-time":"2022-05-09T23:20:50Z","timestamp":1652138450000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":38,"title":["Empagliflozin Ameliorates Diabetic Cardiomyopathy via Attenuating Oxidative Stress and Improving Mitochondrial 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