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However, it remains poorly understood whether maternal diabetes increases the offspring's susceptibility to heart injuries in adulthood. In this study, we observed that cardiac function and structure were comparable between adult offspring born to diabetic mice and their counterparts born to nondiabetic mice at baseline. However, in response to myocardial ischemia\/reperfusion (<jats:styled-content style=\"fixed-case\">MIR<\/jats:styled-content>), diabetic mother offspring exhibited augmented infarct size, cardiac dysfunction, and myocardial apoptosis compared with control, in association with exaggerated activation of mitochondria\u2010 and endoplasmic reticulum (<jats:styled-content style=\"fixed-case\">ER<\/jats:styled-content>) stress\u2010mediated apoptosis pathways and oxidative stress. Molecular analysis showed that the impaired myocardial ischemic tolerance in diabetic mother offspring was mainly attributable to blunted cardiac insulin receptor substrate (<jats:styled-content style=\"fixed-case\">IRS<\/jats:styled-content>)\u20101\/Akt signaling. Furthermore, the effect of maternal melatonin administration on offspring's response to <jats:styled-content style=\"fixed-case\">MIR<\/jats:styled-content> was determined, and the results indicated that melatonin treatment in diabetic dams during pregnancy significantly improved the tolerance to <jats:styled-content style=\"fixed-case\">MIR<\/jats:styled-content> injury in their offspring, via restoring cardiac <jats:styled-content style=\"fixed-case\">IRS<\/jats:styled-content>\u20101\/Akt signaling. Taken together, these data suggest that maternal diabetes predisposes offspring to augmented <jats:styled-content style=\"fixed-case\">MIR<\/jats:styled-content> injury in adulthood, and maternal melatonin supplementation during diabetic pregnancy may hold promise for improving myocardial ischemic tolerance in the offspring.<\/jats:p>","DOI":"10.1111\/jpi.12351","type":"journal-article","created":{"date-parts":[[2016,6,14]],"date-time":"2016-06-14T15:16:13Z","timestamp":1465917373000},"page":"340-352","source":"Crossref","is-referenced-by-count":40,"title":["The impaired myocardial ischemic tolerance in adult offspring of diabetic pregnancy is restored by maternal melatonin treatment"],"prefix":"10.1111","volume":"61","author":[{"given":"Ling","family":"Gao","sequence":"first","affiliation":[{"name":"The International Peace Maternity and Child Health Hospital School of Medicine Shanghai Jiao Tong University  Shanghai 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