Diabetes abolishes the cardioprotection induced by sevoflurane postconditioning in the rat heart in vivo: roles of glycogen synthase kinase-3β and its upstream pathways.J Surg Res. 2012 Nov; 178(1):96-104.JS
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.
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.
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.
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.