title: Long-term insulin treatment restores cardioprotection induced by sufentanil postconditioning in diabetic rat heart.
abstract: Sufentanil, a commonly used opioid analgesic, could mimic ischemia postconditioning to attenuate ischemia reperfusion injury, but this effect might be hindered in diabetic animals by inhibition of glycogen synthase kinase-3β phosphorylation. Also, diabetes can abrogate the cardioprotection of sevoflurane (an inhaled anesthetic) against ischemia reperfusion injury, and short-term insulin treatment does not restore protection by sevoflurane postconditioning. We hypothesized that long-term insulin treatment might restore the cardioprotective effect of sufentanil postconditioning in diabetic rats via phosphorylation of glycogen synthase kinase-3β. Streptozotocin (55 mg/kg)-induced diabetic rats received insulin (Novolin N, 6-8 u/d) for two days or two weeks, then were exposed to 30-min ischemia and 120-min reperfusion. Sufentanil postconditioning was performed 5 min before the onset of reperfusion. Controls included non-diabetic rats, sham surgery for ischemia/reperfusion, and sufentanil vehicle. Infarct size, cardiac troponin I, and phosphorylated glycogen synthase kinase-3β were examined. Sufentanil postconditioning reduced infarct size by 46% in non-diabetic rats (P < 0.001), but diabetes prevented this protective effect. Two-day insulin treatment was not effective, but two-week treatment reduced infarct size by 45% (P < 0.001), reduced cardiac troponin I by 33% (P < 0.001), and increased phosphorylated glycogen synthase kinase-3β levels (P < 0.001) in the diabetic sufentanil postconditioning group. In conclusion, sufentanil-induced cardioprotection was restored by long-term insulin treatment. The underlying mechanism may be increased phosphorylation of glycogen synthase kinase-3β.
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital of Anhui Medical University, Hefei 230000, China.
authors.forename: Yuwen
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital of Anhui Medical University, Hefei 230000, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital of Anhui Medical University, Hefei 230000, China ay_erweigu@163.com.
authors.forename: Erwei
authors.initials: E
authors.lastname: Gu
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital of Anhui Medical University, Hefei 230000, China.
authors.forename: Bingqing
authors.initials: B
authors.lastname: Zhu
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital of Anhui Medical University, Hefei 230000, China.
authors.forename: Xianya
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital of Anhui Medical University, Hefei 230000, China.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Chen
mesh_terms: D000818:Animals; D002316:Cardiotonic Agents / Q000008:administration & dosage*; D002318:Cardiovascular Diseases / Q000188:drug therapy*; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000188:drug therapy*; D003925:Diabetic Angiopathies / Q000188:drug therapy*; D004195:Disease Models, Animal; D007004:Hypoglycemic Agents / Q000008:administration & dosage*; D007328:Insulin / Q000008:administration & dosage*; D057775:Ischemic Postconditioning / Q000379:methods; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control; D017207:Rats, Sprague-Dawley; D017409:Sufentanil / Q000008:administration & dosage*; D016896:Treatment Outcome
chemical_list: D002316:Cardiotonic Agents; D007004:Hypoglycemic Agents; D007328:Insulin; D017409:Sufentanil
keywords: Anesthesia; anesthesiology; cardiovascular; diabetes; insulin; reperfusion