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Here, we investigated whether it plays an anti\u2010apoptotic role in diabetic cardiomyopathy. Sprague\u2010Dawley rats were fed with high\u2010fat diet; then single intraperitoneal injection of streptozotocin was performed. Rats with fasting blood glucose (FBG) higher than 11.1\u00a0mmol\/L were selected as models. Eight weeks after the models were built, rats were treated with nicorandil (7.5\u00a0mg\/kg\u00a0day and 15\u00a0mg\/kg\u00a0day respectively) for 4\u00a0weeks. H9c2 cardiomyocytes were treated with nicorandil and then stimulated with high glucose (33.3\u00a0mmol\/L). TUNEL assay and level of bcl\u20102, bax and caspase\u20103 were measured. 5\u2010HD was used to inhibit nicorandil. Also, PI3K inhibitor (Miltefosine) and mTOR inhibitor (rapamycin) were used to inhibit PI3K\/Akt pathway. The results revealed that nicorandil (both 7.5\u00a0mg\/kg\u00a0day and 15mg\/kg day) treatment can increase the level of NO in the serum and eNOS in the heart of diabetic rats compared with the untreated diabetic group. Nicorandil can also improve relieve cardiac dysfunction and reduce the level of apoptosis. In vitro experiments, nicorandil (100\u00a0\u00b5mol) can attenuate the level of apoptosis stimulated by high glucose significantly in H9C2 cardiomyocyte compared with the untreated group. The effect of nicorandil on apoptosis was blocked by 5\u2010HD, and it was accompanied with inhibition of the phosphorylation of PI3K, Akt, eNOS, and mTOR. After inhibition of PI3K\/Akt pathway, the protective effect of nicorandil is restrained. These results verified that as a NO donor, nicorandil can also inhibit apoptosis in diabetic cardiomyopathy which is mediated by PI3K\/Akt pathway.<\/jats:p>","DOI":"10.1111\/jcmm.14413","type":"journal-article","created":{"date-parts":[[2019,5,27]],"date-time":"2019-05-27T06:39:25Z","timestamp":1558939165000},"page":"5349-5359","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":89,"title":["Nicorandil alleviates apoptosis in diabetic cardiomyopathy through PI3K\/Akt pathway"],"prefix":"10.1111","volume":"23","author":[{"given":"Xuyang","family":"Wang","sequence":"first","affiliation":[{"name":"The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Department of Cardiology Qilu Hospital of Shandong University Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9678-9402","authenticated-orcid":false,"given":"Jinyu","family":"Pan","sequence":"additional","affiliation":[{"name":"Department of Cardiology Shandong Provincial Qianfoshan Hospital of Shandong University Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dian","family":"Liu","sequence":"additional","affiliation":[{"name":"The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Department of Cardiology Qilu Hospital of Shandong University Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingjun","family":"Zhang","sequence":"additional","affiliation":[{"name":"The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Department of Cardiology Qilu Hospital of Shandong University Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaowei","family":"Li","sequence":"additional","affiliation":[{"name":"The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Department of Cardiology Qilu Hospital of Shandong University Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingjing","family":"Tian","sequence":"additional","affiliation":[{"name":"The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of 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