{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T04:27:53Z","timestamp":1789014473774,"version":"build-2803163510"},"reference-count":50,"publisher":"Portland Press Ltd.","issue":"5","content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2016,3,1]]},"abstract":"<jats:p>Patients with diabetes are vulnerable to MI\/R (myocardial ischaemia\/reperfusion) injury, but are not responsive to IPostC (ischaemic post-conditioning) which activates PI3K (phosphoinositide 3-kinase)\/Akt (also known as PKB or protein kinase B) and JAK2 (Janus kinase 2)\/STAT3 (signal transducer and activator of transcription 3) pathways to confer cardioprotection. We hypothesized that increased cardiac PTEN (phosphatase and tensin homologue deleted on chromosome 10), a major negative regulator of PI3K\/Akt, is responsible for the loss of diabetic heart sensitivity to IPostC cardioprotecton. In STZ (streptozotocin)-induced Type\u00a01 diabetic rats subjected to MI\/R (30\u00a0min coronary occlusion and 120\u00a0min reperfusion), the post-ischaemic myocardial infarct size, CK-MB (creatine kinase-MB) and 15-F2t-isoprostane release, as well as cardiac PTEN expression were significantly higher than those in non-diabetic controls, concomitant with more severe cardiac dysfunction and lower cardiac Akt, STAT3 and GSK-3\u03b2 (glycogen synthase kinase 3\u03b2) phosphorylation. IPostC significantly attenuated post-ischaemic infarct size, decreased PTEN expression and further increased Akt, STAT3 and GSK-3\u03b2 phosphorylation in non-diabetic, but not in diabetic rats. Application of the PTEN inhibitor BpV (bisperoxovanadium) (1.0\u00a0mg\/kg) restored IPostC cardioprotection in diabetic rats. HPostC (hypoxic post-conditioning) in combination with PTEN gene knockdown, but not HPostC alone, significantly reduced H\/R (hypoxia\/reoxygenation) injury in cardiac H9c2 cells exposed to high glucose as was evident from reduced apoptotic cell death and JC-1 monomer in cells, accompanied by increased phosphorylation of Akt, STAT3 and GSK-3\u03b2. PTEN inhibition\/gene knockdown mediated restoration of IPostC\/HPostC cardioprotection was completely reversed by the PI3K inhibitor wortmannin, and partially reversed by the JAK2 inhibitor AG490. Increased cardiac PTEN, by impairing PI3K\/Akt and JAK2\/STAT3 pathways, is a major mechanism that rendered diabetic hearts not responsive to post-conditioning cardioprotection.<\/jats:p>","DOI":"10.1042\/cs20150496","type":"journal-article","created":{"date-parts":[[2015,12,15]],"date-time":"2015-12-15T04:23:41Z","timestamp":1450153421000},"page":"377-392","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":75,"title":["Selective inhibition of PTEN preserves ischaemic post-conditioning cardioprotection in STZ-induced Type\u00a01 diabetic rats: role of the PI3K\/Akt and JAK2\/STAT3 pathways"],"prefix":"10.1042","volume":"130","author":[{"given":"Rui","family":"Xue","sequence":"first","affiliation":[{"name":"Department of Anesthesiology, Renmin Hospital of Wuhan University, Wuhan, Hubei, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaoqing","family":"Lei","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Renmin Hospital of Wuhan University, Wuhan, Hubei, China"},{"name":"Department of Anesthesiology, the Second Affiliated Hospital & Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhong-yuan","family":"Xia","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Renmin Hospital of Wuhan University, Wuhan, Hubei, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Renmin Hospital of Wuhan University, Wuhan, Hubei, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingtao","family":"Meng","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Renmin Hospital of Wuhan University, Wuhan, Hubei, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liying","family":"Zhan","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Renmin Hospital of Wuhan University, Wuhan, Hubei, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wating","family":"Su","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Renmin Hospital of Wuhan University, Wuhan, Hubei, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huimin","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Renmin Hospital of Wuhan University, Wuhan, Hubei, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinjin","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Renmin Hospital of Wuhan University, Wuhan, Hubei, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenzhen","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Renmin Hospital, Nanhai District, Foshan, Guangdong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Renmin Hospital of Wuhan University, Wuhan, Hubei, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhengyuan","family":"Xia","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, the Second Affiliated Hospital & Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China"},{"name":"Department of Anesthesiology, University of Hong Kong, Hong Kong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2016,1,26]]},"reference":[{"key":"2021113011071114100_B1","doi-asserted-by":"publisher","first-page":"e29","DOI":"10.1161\/CIR.0000000000000152","article-title":"Heart disease and stroke statistics\u20132015 update: a report from the American Heart Association","volume":"131","author":"Mozaffarian","year":"2015","journal-title":"Circulation"},{"key":"2021113011071114100_B2","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1111\/j.1527-3466.2006.00077.x","article-title":"Oxidative stress as the leading cause of acute myocardial infarction in diabetics","volume":"24","author":"Di Filippo","year":"2006","journal-title":"Cardiovasc. 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