{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T06:05:55Z","timestamp":1784268355045,"version":"3.55.0"},"reference-count":35,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T00:00:00Z","timestamp":1782777600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T00:00:00Z","timestamp":1782777600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin Exp Pharma Physio"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Type 2 Diabetes Mellitus (T2DM) and AF (Atrial Fibrillation) frequently coexist, amplifying cardiovascular risks via shared mitochondrial dysfunction involving metabolic dysregulation, oxidative stress, and inflammation. While the SGLT2 inhibitor dapagliflozin (DAPA) demonstrates cardiorenal protection through mitochondrial improvement, its direct mechanistic actions in T2DM\u2010AF patients remain unknown. Our study aimed to elucidate DAPA's mitochondrial regulatory mechanisms in T2DM\u2010AF to break the vicious cycle of mitochondrial dysfunction remodelling, addressing an unmet clinical need in this high\u2010risk population.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The high\u2010glucose atrial fibrillation (HG\u2010AF) model was established using 30\u2009mM glucose combined with 10\u2009Hz electrical stimulation, followed by validation through glucose uptake assay, electrophysiology, and fibrosis\u2010related protein and calcium transient analysis. Mitochondrial function was evaluated using ROS\/JC\u20101 probes, ATP quantification, and mitochondrial\u2010related protein expression. To investigate the role of DAPA, we assessed its activation of the AMPK\/PGC\u20101\u03b1\/SIRT3 signalling pathway via western blot and further confirmed the mechanism using the AMPK\u03b1 inhibitor Compound C. In addition, a mouse model of HG\u2010AF was established to further validate the in\u00a0vitro results.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Cell experiments showed that after treatment with 30\u2009mM glucose and 10\u2009Hz electrical stimulation, HL\u20101 cells exhibited increased 2\u2010NBDG uptake, decreased Fluo\u20104\u2009AM intensity, upregulation of glucose transporters and fibrosis\u2010related proteins, and disrupted electrophysiological protein expression, confirming the successful establishment of the HG\u2010AF model. DAPA treatment attenuated fibrosis, restored electrophysiological protein expression, decreased Drp1, and increased OPA1 and SOD2 levels. It also enhanced Fluo\u20104\u2009AM intensity, reduced ROS, improved JC\u20101 aggregates, and boosted ATP production. In\u00a0vivo experiments further confirmed that in HG\u2010AF mice, the duration of AF and the RR interval were significantly prolonged, and there was upregulation of CaMKII\/ox\u2010CaMKII, downregulation of ion channel proteins, and elevated levels of fibronectin in cardiac tissue. DAPA treatment activated the AMPK\/PGC\u20101\u03b1\/SIRT3 pathway, reduced the acetylation levels of OPA1 and SOD2, increased ATP levels, and decreased MDA levels. Pretreatment with Compound C abolished the DAPA\u2010induced activation of the aforementioned pathway and the improvement in mitochondrial function.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>In the HG\u2010AF setting, DAPA attenuated cardiomyocyte damage by enhancing mitochondrial function through activation of the AMPK\/PGC\u20101\u03b1\/SIRT3 signalling pathway.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/1440-1681.70143","type":"journal-article","created":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T07:29:54Z","timestamp":1782804594000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Dapagliflozin Improves Mitochondrial Function to Reduce the Risk of Atrial Fibrillation in a High\u2010Glucose Environment by Activating the\n                    <scp>AMPK\/PGC\u20101\u03b1\/SIRT3<\/scp>\n                    Signalling Pathway"],"prefix":"10.1111","volume":"53","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-3046-0384","authenticated-orcid":false,"given":"Xingxing","family":"Li","sequence":"first","affiliation":[{"name":"Department of Cardiology Jinhua People's Hospital  Jinhua Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guibing","family":"He","sequence":"additional","affiliation":[{"name":"Department of Urology Jinhua People's Hospital  Jinhua Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fen","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Cardiology Jinhua People's Hospital  Jinhua Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Cardiology Jinhua People's Hospital  Jinhua Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shu","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Cardiology Jinhua People's Hospital  Jinhua Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-2977-5960","authenticated-orcid":false,"given":"Yang","family":"Dong","sequence":"additional","affiliation":[{"name":"Department of Cardiology Jinhua People's Hospital  Jinhua Zhejiang 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