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We previously found that liver ischemic preconditioning (RLIPC) could limit infarct size post I\/R in non-diabetic rat hearts and further exerted anti-arrhythmic effects in diabetic or non-diabetic rats after myocardial I\/R, however, little is known regarding the effect of RLIPC on infarct-sparing in diabetic hearts. In this study, we evaluated the protective effects of RLIPC on I\/R injury in streptozotocin-induced type 1 diabetic rats. Type 1 diabetes mellitus was induced by one-time intraperitoneal injection of streptozotocin in Sprague\u2013Dawley rats. Rats were exposed to 45\u00a0min of left anterior descend in (LAD) coronary artery occlusion, followed by 3\u00a0h of reperfusion. For liver ischemic preconditioning, four cycles of 5\u00a0min of liver I\/R stimuli were performed before LAD occlusion. The cardioprotective effect of RLIPC was determined in diabetic rats. Compared to non-RLIPC treated DM rats, RLIPC treatment significantly reduced infarct size and cardiac tissue damage, inhibited apoptosis in diabetic hearts post I\/R. RLIPC also improved cardiac functions including LVESP, LVEDP, dp\/dtmax, and \u2212\u2009dp\/dtmax. In addition, RLIPC preserved cardiac morphology by reducing the pathological score post I\/R in diabetic hearts. Finally, Westernblotting showed that RLIPC stimulated phosphorylation of ventricular GSK-3\u03b2 and STAT-5, which are key components of RISK and SAFE signaling pathways. Our study showed that liver ischemic preconditioning retains strong cardioprotective properties in diabetic hearts against myocardial I\/R injury via GSK-3\u03b2\/STAT5 signaling pathway.<\/jats:p>","DOI":"10.1038\/s41598-021-81422-1","type":"journal-article","created":{"date-parts":[[2021,1,21]],"date-time":"2021-01-21T11:03:39Z","timestamp":1611227019000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Remote liver ischemic preconditioning attenuates myocardial ischemia\/reperfusion injury in streptozotocin-induced diabetic rats"],"prefix":"10.1038","volume":"11","author":[{"given":"Xinhao","family":"Liu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hui","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhibing","family":"Yan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lei","family":"Du","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dou","family":"Huang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei Dong","family":"Gao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhaoyang","family":"Hu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2021,1,21]]},"reference":[{"key":"81422_CR1","doi-asserted-by":"publisher","first-page":"736","DOI":"10.1016\/0735-1097(92)90033-j","volume":"20","author":"RM Jacoby","year":"1992","unstructured":"Jacoby, R. 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