TY - JOUR T1 - Diabetes abolishes the cardioprotection induced by sevoflurane postconditioning in the rat heart in vivo: roles of glycogen synthase kinase-3β and its upstream pathways. AU - Tai,Wenjun, AU - Shi,Enyi, AU - Yan,Lihui, AU - Jiang,Xiaojing, AU - Ma,Hong, AU - Ai,Chunyu, Y1 - 2012/03/30/ PY - 2011/12/22/received PY - 2012/01/29/revised PY - 2012/02/09/accepted PY - 2012/4/10/entrez PY - 2012/4/10/pubmed PY - 2013/1/11/medline SP - 96 EP - 104 JF - The Journal of surgical research JO - J Surg Res VL - 178 IS - 1 N2 - BACKGROUND: We measured the cardioprotection afforded by sevoflurane postconditioning in streptozotocin-induced diabetic rats (DRs) and determined the roles of glycogen synthase kinase (GSK), phosphatidylinositol-3-kinase/Akt, and extracellular signal-regulated kinase (ERK1/2) in such a procedure. METHODS: DRs and nondiabetic rats (NDRs) were subjected to a 30-min coronary artery occlusion followed by a 120-min reperfusion. Postconditioning was achieved by inhalation of 1 minimum alveolar concentration sevoflurane at the first 5 min of reperfusion. The infarct size was determined by triphenyltetrazolium chloride staining. Expressions of GSK-3β, Akt, and ERK1/2 were measured using Western blotting. RESULTS: In NDRs, the infarct size was significantly decreased from 53.4% ± 7.6% to 34.9% ± 5.6% by sevoflurane postconditioning (P < 0.01). Such an anti-infarct effect was abolished completely in the DRs, as evidenced by a similar infarct size observed between the sevoflurane-treated and untreated DRs (49.3% ± 8.6% and 49.6% ± 9.3%, respectively, P > 0.05). Direct inhibition of GSK-3β by injection of SB216763 just before the start of reperfusion induced equivalent infarct-sparing effects in both NDRs (37.8% ± 3.9% and 53.4% ± 7.6% in SB216763-treated and untreated NDRs, respectively; P < 0.01) and DRs (38.8% ± 3.2% and 49.3% ± 8.6% in SB216763-treated and untreated DRs, respectively; P < 0.05). Sevoflurane postconditioning remarkably enhanced the phosphorylation of GSK-3β Ser(9), Akt Ser(473), and ERK1/2 in NDRs, which were blocked in DRs. CONCLUSIONS: The cardioprotection induced by sevoflurane postconditioning is abolished by diabetes. This might be due to the impairment of phosphorylation of GSK-3β and its upstream signaling pathways of phosphatidylinositol-3-kinase/Akt and ERK1/2 in the presence of diabetes. SN - 1095-8673 UR - https://www.unboundmedicine.com/medline/citation/22482760/Diabetes_abolishes_the_cardioprotection_induced_by_sevoflurane_postconditioning_in_the_rat_heart_in_vivo:_roles_of_glycogen_synthase_kinase_3β_and_its_upstream_pathways_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0022-4804(12)00092-3 DB - PRIME DP - Unbound Medicine ER -