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Thus, this study has been designed to investigate the role and pharmacological potential of sphingosine\u20101\u2010phosphate in diabetic rat heart. Diabetes was produced in Wistar rats by administration of a low dose of streptozotocin (<jats:styled-content style=\"fixed-case\">STZ<\/jats:styled-content>) (35\u00a0mg\/kg, i.p., once) and feeding a high fat diet (<jats:styled-content style=\"fixed-case\">HFD<\/jats:styled-content>) for 6\u00a0weeks. Isolated rat heart was subjected to 30\u00a0min ischaemia followed by 120\u00a0min of reperfusion (I\/R). The heart was subjected to pre\u2010ischaemic treatment (before ischaemia for 20\u00a0min) and pharmacological preconditioning with the S1P agonist <jats:styled-content style=\"fixed-case\">FTY<\/jats:styled-content>720 (0.6\u00a0<jats:italic>\u03bc<\/jats:italic>mol\/L) with and without atractyloside (an <jats:styled-content style=\"fixed-case\">mPTP<\/jats:styled-content> opener; in the last episode of reperfusion before I\/R). Myocardial infarction was assessed in terms of increase in lactate dehydrogenase (<jats:styled-content style=\"fixed-case\">LDH<\/jats:styled-content>), creatinine kinase\u2010<jats:styled-content style=\"fixed-case\">MB<\/jats:styled-content> (<jats:styled-content style=\"fixed-case\">CK<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">MB<\/jats:styled-content>), myeloperoxidase (<jats:styled-content style=\"fixed-case\">MPO<\/jats:styled-content>) level and infarct size (triphenyltetrazolium chloride staining). Immunohistochemistry analysis was done for assessment of tumour necrosis factor (<jats:styled-content style=\"fixed-case\">TNF<\/jats:styled-content>)\u2010<jats:italic>\u03b1<\/jats:italic> and glycogen synthase kinase (<jats:styled-content style=\"fixed-case\">GSK<\/jats:styled-content>)\u20103<jats:italic>\u03b2<\/jats:italic> level in cardiac tissue. Pre\u2010ischaemic treatment and pharmacological preconditioning with <jats:styled-content style=\"fixed-case\">FTY<\/jats:styled-content>720 significantly decreased I\/R\u2010induced myocardial infarction, <jats:styled-content style=\"fixed-case\">TNF<\/jats:styled-content>\u2010alpha, <jats:styled-content style=\"fixed-case\">GSK<\/jats:styled-content>\u20103<jats:italic>\u03b2<\/jats:italic> level and release of <jats:styled-content style=\"fixed-case\">LDH<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">CK<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">MB<\/jats:styled-content> as compared to control group. The cardioprotective effect of S1P agonist was significantly attenuated by atractyloside. It may be concluded that S1P agonist <jats:styled-content style=\"fixed-case\">FTY<\/jats:styled-content>720 prevents the diabetic heart from ischaemic reperfusion injury, possibly through inhibition of <jats:styled-content style=\"fixed-case\">GSK<\/jats:styled-content>\u20103<jats:italic>\u03b2<\/jats:italic> and regulation of opening of mitochondrial permeability transition pore.<\/jats:p>","DOI":"10.1111\/1440-1681.12516","type":"journal-article","created":{"date-parts":[[2015,11,19]],"date-time":"2015-11-19T10:20:43Z","timestamp":1447928443000},"page":"166-173","source":"Crossref","is-referenced-by-count":34,"title":["Mechanism of sphingosine\u20101\u2010phosphate induced cardioprotection against I\/R injury in diabetic rat heart: Possible involvement of glycogen synthase kinase 3<i>\u03b2<\/i> and mitochondrial permeability transition pore"],"prefix":"10.1111","volume":"43","author":[{"given":"Ajay","family":"Rana","sequence":"first","affiliation":[{"name":"Department of Pharmacology ISF College of Pharmacy Moga Punjab India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Saurabh","family":"Sharma","sequence":"additional","affiliation":[{"name":"Department of Pharmacology ISF College of Pharmacy Moga Punjab India"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2016,1,28]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1177\/0267659114536760"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cardiores.2003.09.025"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.74.5.1124"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0008-6363(02)00455-8"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2003.034231"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1161\/hh2301.100350"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.275.19.14281"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm1103"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.01331.2006"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2004-02-0452"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00395-010-0130-3"},{"key":"e_1_2_7_13_1","first-page":"629","article-title":"Ischemic preconditioning: Protection against myocardial necrosis and apoptosis","volume":"3","author":"Iliodromitis KE","year":"2007","journal-title":"Vasc. 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