{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T14:26:16Z","timestamp":1768314376593,"version":"3.49.0"},"reference-count":43,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2020,10,8]],"date-time":"2020-10-08T00:00:00Z","timestamp":1602115200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81370331"],"award-info":[{"award-number":["81370331"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Diabetes Invest"],"published-print":{"date-parts":[[2021,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Aims\/Introduction<\/jats:title><jats:p>Diabetic cardiomyopathy is a type of myocardial disease. It causes left ventricular hypertrophy, followed by diastolic and systolic dysfunction, eventually leading to congestive heart failure. However, the underlying mechanism still requires further elucidation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials and Methods<\/jats:title><jats:p>A high\u2010glucose zebrafish model was constructed by administering streptozocin intraperitoneally to enhance the development of cardiomyopathy and then treated with adenosine monophosphate\u2010activated protein kinase (AMPK) activator. Cardiac structure and function, and protein and gene expression were then analyzed. Cardiomyocytes (CMs) culture <jats:italic>in\u00a0vitro<\/jats:italic> using lentivirus were used for detection of AMPK, p53 and Kr\u00fcppel\u2010like factor\u00a02a (klf2a) gene expression.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In the hyperglycemia group, electrocardiogram findings showed arrhythmia, echocardiography results showed heart enlargement and dysfunction, and many differences, such as increased apoptosis and myocardial fiber loss, were observed. The phospho\u2010AMPK and klf2a expression were downregulated, and p53 expression was upregulated. Activation of phospho\u2010AMPK reduced p53 and increased klf2a expression, alleviated apoptosis in CMs and improved cardiac function in the hyperglycemic zebrafish. <jats:italic>In\u00a0vitro<\/jats:italic> knockdown system of AMPK, p53 and klf2a using lentivirus illustrated an increased p53 expression and decreased klf2a expression in CMs by inhibiting AMPK. Repression of p53 and upregulation of klf2a expression were observed, but no changes in the expression of AMPK and its phosphorylated type.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>In the model of streptozocin\u2010induced hyperglycemia zebrafish, the reduction of phosphorylated AMPK increased p53, which led to KLF2a decrease to facilitate apoptosis of CMs, inducing the cardiac remodeling and cardiac dysfunction. These results can be reversed by AMPK activator, which means the AMPK\u2013p53\u2013klf2a pathway might be a potential target for diabetic cardiomyopathy intervention.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jdi.13393","type":"journal-article","created":{"date-parts":[[2020,9,3]],"date-time":"2020-09-03T13:20:19Z","timestamp":1599139219000},"page":"320-333","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Effect of adenosine monophosphate\u2010activated protein kinase\u2013p53\u2013Kr\u00fcppel\u2010like factor\u00a02a pathway in hyperglycemia\u2010induced cardiac remodeling in adult zebrafish"],"prefix":"10.1111","volume":"12","author":[{"given":"Qiuyun","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Cardiology Ruijin Hospital Shanghai Jiaotong University School of Medicine Shanghai 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