{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T18:33:47Z","timestamp":1791570827319,"version":"4.3.4"},"reference-count":57,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2018,4,14]],"date-time":"2018-04-14T00:00:00Z","timestamp":1523664000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2018,4,14]],"date-time":"2018-04-14T00:00:00Z","timestamp":1523664000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81670354"],"award-info":[{"award-number":["81670354"]}],"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":["81600235"],"award-info":[{"award-number":["81600235"]}],"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":["81770243"],"award-info":[{"award-number":["81770243"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Pineal Research"],"published-print":{"date-parts":[[2018,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Myocardial contractile dysfunction is associated with an increase in mitochondrial fission in patients with diabetes. However, whether mitochondrial fission directly promotes diabetes\u2010induced cardiac dysfunction is still unknown. Melatonin exerts a substantial influence on the regulation of mitochondrial fission\/fusion. This study investigated whether melatonin protects against diabetes\u2010induced cardiac dysfunction via regulation of mitochondrial fission\/fusion and explored its underlying mechanisms. Here, we show that melatonin prevented diabetes\u2010induced cardiac dysfunction by inhibiting dynamin\u2010related protein 1 (Drp1)\u2010mediated mitochondrial fission. Melatonin treatment decreased Drp1 expression, inhibited mitochondrial fragmentation, suppressed oxidative stress, reduced cardiomyocyte apoptosis, improved mitochondrial function and cardiac function in streptozotocin (\n                    <jats:styled-content style=\"fixed-case\">STZ<\/jats:styled-content>\n                    )\u2010induced diabetic mice, but not in\n                    <jats:styled-content style=\"fixed-case\">SIRT<\/jats:styled-content>\n                    1\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    diabetic mice. In high glucose\u2010exposed H9c2 cells, melatonin treatment increased the expression of\n                    <jats:styled-content style=\"fixed-case\">SIRT<\/jats:styled-content>\n                    1 and\n                    <jats:styled-content style=\"fixed-case\">PGC<\/jats:styled-content>\n                    \u20101\u03b1 and inhibited Drp1\u2010mediated mitochondrial fission and mitochondria\u2010derived superoxide production. In contrast,\n                    <jats:styled-content style=\"fixed-case\">SIRT<\/jats:styled-content>\n                    1 or\n                    <jats:styled-content style=\"fixed-case\">PGC<\/jats:styled-content>\n                    \u20101\u03b1 si\n                    <jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content>\n                    knockdown blunted the inhibitory effects of melatonin on Drp1 expression and mitochondrial fission. These data indicated that melatonin exerted its cardioprotective effects by reducing Drp1\u2010mediated mitochondrial fission in a\n                    <jats:styled-content style=\"fixed-case\">SIRT<\/jats:styled-content>\n                    1\/\n                    <jats:styled-content style=\"fixed-case\">PGC<\/jats:styled-content>\n                    \u20101\u03b1\u2010dependent manner. Moreover, chromatin immunoprecipitation analysis revealed that\n                    <jats:styled-content style=\"fixed-case\">PGC<\/jats:styled-content>\n                    \u20101\u03b1 directly regulated the expression of Drp1 by binding to its promoter. Inhibition of mitochondrial fission with Drp1 inhibitor mdivi\u20101 suppressed oxidative stress, alleviated mitochondrial dysfunction and cardiac dysfunction in diabetic mice. These findings show that melatonin attenuates the development of diabetes\u2010induced cardiac dysfunction by preventing mitochondrial fission through\n                    <jats:styled-content style=\"fixed-case\">SIRT<\/jats:styled-content>\n                    1\u2010\n                    <jats:styled-content style=\"fixed-case\">PGC<\/jats:styled-content>\n                    1\u03b1 pathway, which negatively regulates the expression of Drp1 directly. Inhibition of mitochondrial fission may be a potential target for delaying cardiac complications in patients with diabetes.\n                  <\/jats:p>","DOI":"10.1111\/jpi.12491","type":"journal-article","created":{"date-parts":[[2018,3,25]],"date-time":"2018-03-25T15:21:15Z","timestamp":1521991275000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":349,"title":["Melatonin prevents\n                    <scp>D<\/scp>\n                    rp1\u2010mediated mitochondrial fission in diabetic hearts through\n                    <scp>SIRT<\/scp>\n                    1\u2010\n                    <scp>PGC<\/scp>\n                    1\u03b1 pathway"],"prefix":"10.1111","volume":"65","author":[{"given":"Mingge","family":"Ding","sequence":"first","affiliation":[{"name":"Department of Cardiology and Department of Geriatrics Xi'an Central Hospital Xi'an Jiaotong University  Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Na","family":"Feng","sequence":"additional","affiliation":[{"name":"Department of Physiology National Key Discipline of Cell Biology School of Basic Medicine Fourth Military Medical University  Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daishi","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Endocrinology Affiliated Zhongshan Hospital of Dalian University  Dalian China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiahao","family":"Feng","sequence":"additional","affiliation":[{"name":"Department of Physiology National Key Discipline of Cell Biology School of Basic Medicine Fourth Military Medical University  Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zeyang","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Physiology National Key Discipline of Cell Biology School of Basic 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