{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T22:18:06Z","timestamp":1790201886875,"version":"4.1.0"},"reference-count":72,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2020,10,24]],"date-time":"2020-10-24T00:00:00Z","timestamp":1603497600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81700264"],"award-info":[{"award-number":["81700264"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005047","name":"Natural Science Foundation of Liaoning Province","doi-asserted-by":"publisher","award":["20170540973"],"award-info":[{"award-number":["20170540973"]}],"id":[{"id":"10.13039\/501100005047","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005047","name":"Natural Science Foundation of Liaoning Province","doi-asserted-by":"publisher","award":["2020\u2010MS\u2010036"],"award-info":[{"award-number":["2020\u2010MS\u2010036"]}],"id":[{"id":"10.13039\/501100005047","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":[[2021,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Targeting mitochondrial quality control with melatonin has been found promising for attenuating diabetic cardiomyopathy (DCM), although the underlying mechanisms remain largely undefined. Activation of SIRT6 and melatonin membrane receptors exerts cardioprotective effects while little is known about their roles during DCM. Using high\u2010fat diet\u2010streptozotocin\u2010induced diabetic rat model, we found that prolonged diabetes significantly decreased nocturnal circulatory melatonin and heart melatonin levels, reduced the expressions of cardiac melatonin membrane receptors, and decreased myocardial SIRT6 and AMPK\u2010PGC\u20101\u03b1\u2010AKT signaling. 16\u00a0weeks of melatonin treatment inhibited the progression of DCM and the following myocardial ischemia\u2010reperfusion (MI\/R) injury by reducing mitochondrial fission, enhancing mitochondrial biogenesis and mitophagy via re\u2010activating SIRT6 and AMPK\u2010PGC\u20101\u03b1\u2010AKT signaling. After the induction of diabetes, adeno\u2010associated virus carrying SIRT6\u2010specific small hairpin RNA or luzindole was delivered to the animals. We showed that SIRT6 knockdown or antagonizing melatonin receptors abolished the protective effects of melatonin against mitochondrial dysfunction as evidenced by aggravated mitochondrial fission and reduced mitochondrial biogenesis and mitophagy. Additionally, SIRT6 shRNA or luzindole inhibited melatonin\u2010induced AMPK\u2010PGC\u20101\u03b1\u2010AKT activation as well as its cardioprotective actions. Collectively, we demonstrated that long\u2010term melatonin treatment attenuated the progression of DCM and reduced myocardial vulnerability to MI\/R injury through preserving mitochondrial quality control. Melatonin membrane receptor\u2010mediated SIRT6\u2010AMPK\u2010PGC\u20101\u03b1\u2010AKT axis played a key role in this process. Targeting SIRT6 with melatonin treatment may be a promising strategy for attenuating DCM and reducing myocardial vulnerability to ischemia\u2010reperfusion injury in diabetic patients.<\/jats:p>","DOI":"10.1111\/jpi.12698","type":"journal-article","created":{"date-parts":[[2020,10,5]],"date-time":"2020-10-05T06:10:41Z","timestamp":1601878241000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":191,"title":["Melatonin attenuates diabetic cardiomyopathy and reduces myocardial vulnerability to ischemia\u2010reperfusion injury by improving mitochondrial quality control: Role of SIRT6"],"prefix":"10.1111","volume":"70","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5953-5016","authenticated-orcid":false,"given":"Li\u2010Ming","family":"Yu","sequence":"first","affiliation":[{"name":"Department of Cardiovascular Surgery General Hospital of Northern Theater Command  Shenyang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xue","family":"Dong","sequence":"additional","affiliation":[{"name":"Outpatient Department of Liaoning Military Region General Hospital of Northern Theater Command  Shenyang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao\u2010Dong","family":"Xue","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Surgery General Hospital of Northern Theater Command  Shenyang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shu","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Surgery General Hospital of Northern Theater Command  Shenyang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xu","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Surgery General Hospital of Northern Theater Command  Shenyang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yin\u2010Li","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Surgery General Hospital of Northern Theater Command  Shenyang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi\u2010Shang","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Surgery General Hospital of Northern Theater Command  Shenyang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Surgery General Hospital of Northern Theater Command  Shenyang China"},{"name":"Graduate School Liaoning University of Traditional Chinese Medicine  Shenyang China"},{"name":"Department of Cardiothoracic Surgery The First Affiliated Hospital of Jinzhou Medical University  Jinzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Surgery General Hospital of Northern Theater Command  Shenyang China"},{"name":"Graduate School China Medical University  Shenyang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan\u2010Xiao","family":"Liang","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Surgery General Hospital of Northern Theater Command  Shenyang China"},{"name":"Department of Cardiac Surgery Shengjing Hospital of China Medical University  Shenyang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1163-2359","authenticated-orcid":false,"given":"Yang","family":"Yang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Resource Biology and Biotechnology in Western China Ministry of Education Faculty of Life Sciences Northwest University  Xi\u2019an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6523-7488","authenticated-orcid":false,"given":"Hui\u2010Shan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Surgery General Hospital of Northern Theater Command  Shenyang China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,10,24]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.115.015357"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.106.679597"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12933-017-0638-z"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10741-012-9313-3"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/jpi.12375"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/jpi.12269"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2017.11.023"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41569-018-0059-z"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.113.008476"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep41337"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.118.033552"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/jpi.12471"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/jpi.12378"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/jpi.12571"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-014-1579-2"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2013.7649"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2013.2710"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-079X.2005.00287.x"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-079X.2012.01001.x"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmet.2019.07.007"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exger.2009.02.002"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-079X.2008.00604.x"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.13536"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1111\/jpi.12391"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41420-019-0168-4"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2961"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2017.00394"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2018.03.012"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1111\/jpi.12491"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00666.2014"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1111\/jpi.12433"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.117.311143"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1617288114"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10495-017-1378-y"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1155\/2019\/7670854"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2015.12.025"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10741-016-9531-1"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.7150\/thno.33684"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.emboj.7601963"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.118.314607"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2016.07.001"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2018.09.009"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2017.12.019"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mito.2015.10.001"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbagen.2016.10.022"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2015.05.020"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1111\/jpi.12542"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1111\/jpi.12056"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00395-018-0682-1"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.119.315252"},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2014.06.023"},{"key":"e_1_2_8_53_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.13802"},{"key":"e_1_2_8_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2018.04.009"},{"key":"e_1_2_8_55_1","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2018.7597"},{"key":"e_1_2_8_56_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0610290104"},{"key":"e_1_2_8_57_1","doi-asserted-by":"publisher","DOI":"10.1111\/jpi.12490"},{"key":"e_1_2_8_58_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2019.03.043"},{"key":"e_1_2_8_59_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2009.12.041"},{"key":"e_1_2_8_60_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2008.10.052"},{"key":"e_1_2_8_61_1","doi-asserted-by":"publisher","DOI":"10.2174\/1874609811306010016"},{"key":"e_1_2_8_62_1","doi-asserted-by":"publisher","DOI":"10.1100\/2012\/640389"},{"key":"e_1_2_8_63_1","doi-asserted-by":"publisher","DOI":"10.2337\/db18-0956"},{"key":"e_1_2_8_64_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-079X.2011.00931.x"},{"key":"e_1_2_8_65_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.10-6756"},{"key":"e_1_2_8_66_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00395-016-0531-z"},{"key":"e_1_2_8_67_1","doi-asserted-by":"publisher","DOI":"10.7150\/ijbs.29323"},{"key":"e_1_2_8_68_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13578-020-00402-6"},{"key":"e_1_2_8_69_1","doi-asserted-by":"publisher","DOI":"10.1111\/jpi.12299"},{"key":"e_1_2_8_70_1","doi-asserted-by":"publisher","DOI":"10.1111\/jpi.12419"},{"key":"e_1_2_8_71_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.201900767R"},{"key":"e_1_2_8_72_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.55828"},{"key":"e_1_2_8_73_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clnu.2017.12.004"}],"container-title":["Journal of Pineal Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jpi.12698","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/jpi.12698","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jpi.12698","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,4]],"date-time":"2023-09-04T17:16:56Z","timestamp":1693847816000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/jpi.12698"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,10,24]]},"references-count":72,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2021,1]]}},"alternative-id":["10.1111\/jpi.12698"],"URL":"https:\/\/doi.org\/10.1111\/jpi.12698","archive":["Portico"],"relation":{},"ISSN":["0742-3098","1600-079X"],"issn-type":[{"value":"0742-3098","type":"print"},{"value":"1600-079X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,10,24]]},"assertion":[{"value":"2020-06-02","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-09-02","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-10-24","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e12698"}}