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SB216763 (but not morphine) reduced infarct size in DBRs (44 \u00b1 1* and 55 \u00b1 2%, respectively), while both agents reduced infarct size in NDBRs versus untreated NDBRs or DBRs (44 \u00b1 3*, 42 \u00b1 3*, 60 \u00b1 2, and 56 \u00b1 2%, respectively, *P &amp;lt; 0.001). Morphine-induced phospho- (P-)GSK3\u03b2 was reduced 5 min after reperfusion in DBRs compared with NDBRs (0.83 \u00b1 0.29 and 1.94 \u00b1 0.12 [P &amp;lt; 0.05] pg\/\u03bcg tissue, respectively). The GSK3\u03b2 mediators, P-Akt, P\u2013extracellular signal\u2013related kinase (ERK)1, and P\u2013signal transducer and activator of transcription (STAT)3, were also significantly reduced in untreated DBR compared with NDBR rats. Morphine-induced elevations of P-Akt, P-ERK1, P-p70s6, P\u2013janus-activated kinase-2, and P-STAT3 in NDBRs were also blunted in DBRs. H9C2 cells raised in 25 mmol\/l compared with 5.56 mmol\/l glucose media also demonstrated reduced morphine-induced P-GSK3\u03b2, P-Akt, P-STAT3, and P-ERK1 after 15 min. Hence, acute GSK inhibition may provide a novel therapeutic strategy for diabetic patients during an acute myocardial infarction, whereas morphine is less effective due to signaling events that adversely affect GSK3\u03b2.<\/jats:p>","DOI":"10.2337\/db06-0907","type":"journal-article","created":{"date-parts":[[2006,12,27]],"date-time":"2006-12-27T18:46:11Z","timestamp":1167245171000},"page":"127-136","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":115,"title":["Diabetes Abolishes Morphine-Induced Cardioprotection via Multiple Pathways Upstream of Glycogen Synthase Kinase-3\u03b2"],"prefix":"10.2337","volume":"56","author":[{"given":"Eric R.","family":"Gross","sequence":"first","affiliation":[{"name":"From the Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee, Wisconsin"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna K.","family":"Hsu","sequence":"additional","affiliation":[{"name":"From the Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee, Wisconsin"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Garrett J.","family":"Gross","sequence":"additional","affiliation":[{"name":"From the Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee, Wisconsin"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1167","reference":[{"key":"2022031207465183600_R1","doi-asserted-by":"crossref","unstructured":"Gerstein HC, Pais P, Pogue J, Yusuf S: Relationship of glucose and insulin levels to the risk of myocardial infarction: a case-control study. 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