{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T20:18:35Z","timestamp":1792527515132,"version":"4.5.0"},"reference-count":129,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2017,2,19]],"date-time":"2017-02-19T00:00:00Z","timestamp":1487462400000},"content-version":"vor","delay-in-days":49,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Oxidative Medicine and Cellular Longevity"],"published-print":{"date-parts":[[2017,1]]},"abstract":"<jats:p>Diabetes mellitus (DM) displays a high morbidity. The diabetic heart is susceptible to myocardial ischemia\/reperfusion (MI\/R) injury. Impaired activation of prosurvival pathways, endoplasmic reticulum (ER) stress, increased basal oxidative state, and decreased antioxidant defense and autophagy may render diabetic hearts more vulnerable to MI\/R injury. Oxidative stress and mTOR signaling crucially regulate cardiometabolism, affecting MI\/R injury under diabetes. Producing reactive oxygen species (ROS) and reactive nitrogen species (RNS), uncoupling nitric oxide synthase (NOS), and disturbing the mitochondrial quality control may be three major mechanisms of oxidative stress. mTOR signaling presents both cardioprotective and cardiotoxic effects on the diabetic heart, which interplays with oxidative stress directly or indirectly. Antihyperglycemic agent metformin and newly found free radicals scavengers, Sirt1 and CTRP9, may serve as promising pharmacological therapeutic targets. In this review, we will focus on the role of oxidative stress and mTOR signaling in the pathophysiology of MI\/R injury in diabetes and discuss potential mechanisms and their interactions in an effort to provide some evidence for cardiometabolic targeted therapies for ischemic heart disease (IHD).<\/jats:p>","DOI":"10.1155\/2017\/6437467","type":"journal-article","created":{"date-parts":[[2017,2,19]],"date-time":"2017-02-19T21:02:14Z","timestamp":1487538134000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":141,"title":["Insights for Oxidative Stress and mTOR Signaling in Myocardial Ischemia\/Reperfusion Injury under Diabetes"],"prefix":"10.1155","volume":"2017","author":[{"given":"Dajun","family":"Zhao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2059-1912","authenticated-orcid":false,"given":"Jian","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4004-9883","authenticated-orcid":false,"given":"Lifang","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,2,19]]},"reference":[{"key":"e_1_2_8_1_2","doi-asserted-by":"publisher","DOI":"10.1161\/cir.0000000000000366"},{"key":"e_1_2_8_2_2","doi-asserted-by":"publisher","DOI":"10.1111\/echo.12389"},{"key":"e_1_2_8_3_2","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvu223"},{"key":"e_1_2_8_4_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurjhf\/hfr125"},{"key":"e_1_2_8_5_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.physiol.65.092101.142243"},{"key":"e_1_2_8_6_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.physiol.63.1.391"},{"key":"e_1_2_8_7_2","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00008.2011"},{"key":"e_1_2_8_8_2","doi-asserted-by":"publisher","DOI":"10.1253\/circj.cj-13-0236"},{"key":"e_1_2_8_9_2","doi-asserted-by":"publisher","DOI":"10.1056\/nejmoa1415921"},{"key":"e_1_2_8_10_2","doi-asserted-by":"publisher","DOI":"10.2741\/2205"},{"key":"e_1_2_8_11_2","doi-asserted-by":"publisher","DOI":"10.1056\/nejmoa1509225"},{"key":"e_1_2_8_12_2","doi-asserted-by":"publisher","DOI":"10.2337\/db13-1896"},{"key":"e_1_2_8_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cardiores.2007.06.022"},{"key":"e_1_2_8_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2010.07.033"},{"key":"e_1_2_8_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2009.07.031"},{"key":"e_1_2_8_16_2","doi-asserted-by":"publisher","DOI":"10.1056\/nejmra0800239"},{"key":"e_1_2_8_17_2","doi-asserted-by":"publisher","DOI":"10.2337\/db13-0340"},{"key":"e_1_2_8_18_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.res.0000261924.76669.36"},{"key":"e_1_2_8_19_2","doi-asserted-by":"publisher","DOI":"10.2337\/dc08-0898"},{"key":"e_1_2_8_20_2","doi-asserted-by":"publisher","DOI":"10.1186\/1475-2840-11-67"},{"key":"e_1_2_8_21_2","doi-asserted-by":"publisher","DOI":"10.1097\/aln.0b013e31820efafd"},{"key":"e_1_2_8_22_2","doi-asserted-by":"publisher","DOI":"10.1124\/pr.113.008300"},{"key":"e_1_2_8_23_2","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2010.3360"},{"key":"e_1_2_8_24_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00395-010-0130-3"},{"key":"e_1_2_8_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2009.03.019"},{"key":"e_1_2_8_26_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11010-010-0589-0"},{"key":"e_1_2_8_27_2","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2010.3722"},{"key":"e_1_2_8_28_2","doi-asserted-by":"publisher","DOI":"10.1161\/circulationaha.108.815043"},{"key":"e_1_2_8_29_2","doi-asserted-by":"publisher","DOI":"10.1210\/er.2007-0015"},{"key":"e_1_2_8_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2014.05.006"},{"key":"e_1_2_8_31_2","doi-asserted-by":"publisher","DOI":"10.2337\/db09-0158"},{"key":"e_1_2_8_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.niox.2014.12.013"},{"key":"e_1_2_8_33_2","doi-asserted-by":"publisher","DOI":"10.1155\/2016\/1902025"},{"key":"e_1_2_8_34_2","doi-asserted-by":"publisher","DOI":"10.1210\/en.2007-0877"},{"key":"e_1_2_8_35_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1582-4934.2012.01661.x"},{"key":"e_1_2_8_36_2","doi-asserted-by":"publisher","DOI":"10.1089\/dna.2012.1739"},{"key":"e_1_2_8_37_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.106.664250"},{"key":"e_1_2_8_38_2","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvp085"},{"key":"e_1_2_8_39_2","doi-asserted-by":"publisher","DOI":"10.1186\/1475-2840-10-97"},{"key":"e_1_2_8_40_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0020975"},{"key":"e_1_2_8_41_2","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2013.5416"},{"key":"e_1_2_8_42_2","doi-asserted-by":"publisher","DOI":"10.4161\/auto.18980"},{"key":"e_1_2_8_43_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00395-014-0423-z"},{"key":"e_1_2_8_44_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12933-015-0313-1"},{"key":"e_1_2_8_45_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2011.11.004"},{"key":"e_1_2_8_46_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0735-1097(02)01969-1"},{"key":"e_1_2_8_47_2","doi-asserted-by":"publisher","DOI":"10.1172\/jci23354"},{"key":"e_1_2_8_48_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2008.09.055"},{"key":"e_1_2_8_49_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00267.2009"},{"key":"e_1_2_8_50_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0047-6374(02)00185-9"},{"key":"e_1_2_8_51_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.m007383200"},{"key":"e_1_2_8_52_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.m011695200"},{"key":"e_1_2_8_53_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.060028097"},{"key":"e_1_2_8_54_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.01012.2008"},{"key":"e_1_2_8_55_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2009.12.003"},{"key":"e_1_2_8_56_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature09599"},{"key":"e_1_2_8_57_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00331.2011"},{"key":"e_1_2_8_58_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2010.12.010"},{"key":"e_1_2_8_59_2","doi-asserted-by":"publisher","DOI":"10.1038\/cdd.2012.81"},{"key":"e_1_2_8_60_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00040.2006"},{"key":"e_1_2_8_61_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2006.01.016"},{"key":"e_1_2_8_62_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature11861"},{"key":"e_1_2_8_63_2","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.125773"},{"key":"e_1_2_8_64_2","doi-asserted-by":"publisher","DOI":"10.1172\/jci43008c1"},{"key":"e_1_2_8_65_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2012.03.017"},{"key":"e_1_2_8_66_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00241.2012"},{"key":"e_1_2_8_67_2","doi-asserted-by":"publisher","DOI":"10.4161\/cc.8.11.8619"},{"key":"e_1_2_8_68_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M611782200"},{"key":"e_1_2_8_69_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2011.02.009"},{"key":"e_1_2_8_70_2","doi-asserted-by":"publisher","DOI":"10.1113\/expphysiol.2012.064832"},{"key":"e_1_2_8_71_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0019237"},{"key":"e_1_2_8_72_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcm.2012.04.005"},{"key":"e_1_2_8_73_2","doi-asserted-by":"publisher","DOI":"10.1007\/s40256-014-0089-9"},{"key":"e_1_2_8_74_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2010.08.017"},{"key":"e_1_2_8_75_2","doi-asserted-by":"publisher","DOI":"10.1093\/toxsci\/kfr181"},{"key":"e_1_2_8_76_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2015.05.041"},{"key":"e_1_2_8_77_2","first-page":"1173","article-title":"Translating cell survival and cell longevity into treatment strategies with SIRT1","volume":"52","author":"Maiese K.","year":"2011","journal-title":"Romanian Journal of Morphology and Embryology"},{"key":"e_1_2_8_78_2","doi-asserted-by":"publisher","DOI":"10.1172\/jci46243"},{"key":"e_1_2_8_79_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1008647107"},{"key":"e_1_2_8_80_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00337.2010"},{"key":"e_1_2_8_81_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2010.12.007"},{"key":"e_1_2_8_82_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2013.03.013"},{"key":"e_1_2_8_83_2","doi-asserted-by":"publisher","DOI":"10.1161\/circulationaha.111.078212"},{"key":"e_1_2_8_84_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.toxlet.2015.06.005"},{"key":"e_1_2_8_85_2","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.E08-12-1249"},{"key":"e_1_2_8_86_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00392-010-0278-8"},{"key":"e_1_2_8_87_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2012.09.007"},{"key":"e_1_2_8_88_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00395-015-0486-5"},{"key":"e_1_2_8_89_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00008.2015"},{"key":"e_1_2_8_90_2","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.12369"},{"key":"e_1_2_8_91_2","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2009.2940"},{"key":"e_1_2_8_92_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature06322"},{"key":"e_1_2_8_93_2","doi-asserted-by":"publisher","DOI":"10.1096\/fj.01-0658com"},{"key":"e_1_2_8_94_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-6143.2006.01433.x"},{"key":"e_1_2_8_95_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature05029"},{"key":"e_1_2_8_96_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.113.003638"},{"key":"e_1_2_8_97_2","doi-asserted-by":"publisher","DOI":"10.4161\/auto.5.5.8504"},{"key":"e_1_2_8_98_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11010-009-0377-x"},{"key":"e_1_2_8_99_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms5425"},{"key":"e_1_2_8_100_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.110.977066"},{"key":"e_1_2_8_101_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11010-010-0431-8"},{"key":"e_1_2_8_102_2","doi-asserted-by":"publisher","DOI":"10.1097\/hjh.0000000000000149"},{"key":"e_1_2_8_103_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncb2822"},{"key":"e_1_2_8_104_2","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvr002"},{"key":"e_1_2_8_105_2","doi-asserted-by":"publisher","DOI":"10.1161\/jaha.113.004796"},{"key":"e_1_2_8_106_2","doi-asserted-by":"publisher","DOI":"10.2337\/db07-1098"},{"key":"e_1_2_8_107_2","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.113.02619"},{"key":"e_1_2_8_108_2","doi-asserted-by":"publisher","DOI":"10.1155\/2016\/2961954"},{"key":"e_1_2_8_109_2","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.55.1.120"},{"key":"e_1_2_8_110_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1681.2010.05470.x"},{"key":"e_1_2_8_111_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2016.01.001"},{"key":"e_1_2_8_112_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcb.2014.04.002"},{"key":"e_1_2_8_113_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1474-9726.2010.00548.x"},{"key":"e_1_2_8_114_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2011.05.004"},{"key":"e_1_2_8_115_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbagen.2013.10.034"},{"key":"e_1_2_8_116_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2008.04.027"},{"key":"e_1_2_8_117_2","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.12804"},{"key":"e_1_2_8_118_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00110.2013"},{"key":"e_1_2_8_119_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00593.2013"},{"key":"e_1_2_8_120_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00395-012-0315-z"},{"key":"e_1_2_8_121_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.01518-14"},{"key":"e_1_2_8_122_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M112.357939"},{"key":"e_1_2_8_123_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2013.02.008"},{"key":"e_1_2_8_124_2","doi-asserted-by":"publisher","DOI":"10.2337\/db09-1324"},{"key":"e_1_2_8_125_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature09076"},{"key":"e_1_2_8_126_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.24.21.9508-9516.2004"},{"key":"e_1_2_8_127_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.24.15.6710-6718.2004"},{"key":"e_1_2_8_128_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2006.10.007"},{"key":"e_1_2_8_129_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1013800108"}],"container-title":["Oxidative Medicine and Cellular Longevity"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/downloads.hindawi.com\/journals\/omcl\/2017\/6437467.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/downloads.hindawi.com\/journals\/omcl\/2017\/6437467.xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1155\/2017\/6437467","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,8,6]],"date-time":"2024-08-06T04:39:30Z","timestamp":1722919170000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1155\/2017\/6437467"}},"subtitle":[],"editor":[{"given":"Fl\u00e1vio","family":"Reis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2017,1]]},"references-count":129,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2017,1]]}},"alternative-id":["10.1155\/2017\/6437467"],"URL":"https:\/\/doi.org\/10.1155\/2017\/6437467","archive":["Portico"],"relation":{},"ISSN":["1942-0900","1942-0994"],"issn-type":[{"value":"1942-0900","type":"print"},{"value":"1942-0994","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,1]]},"assertion":[{"value":"2016-09-08","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2017-01-04","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2017-02-19","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"6437467"}}