Effects of glucagon-like peptide 1 analogs in combination with insulin on myocardial infarct size in rats with type 2 diabetes mellitus

作     者：Vladislav A Zykov Taisiia P Tuchina Denis A Lebedev Irina B Krylova Alina Y Babenko Elvira V Kuleshova Elena N Grineva Alekber A Bayramov Michael M Galagudza 

作者机构：Almazov National Medical Research CentreSt-Petersburg 197341Russia Institute of Experimental MedicineSt-Petersburg 197376Russia 

出 版 物：《World Journal of Diabetes》 (世界糖尿病杂志（英文版）（电子版）)

年 卷 期：2018年第9卷第9期

页      面：149-156页

核心收录：

学科分类：10[医学] 

基　　金：Supported by Russian Science Foundation No.17-75-30052 

主　　题：Glucagon-like peptide-1 analog Insulin Myocardial ischemia-reperfusion injury Infarct size Type 2 diabetes mellitus Rats Experimental research 

摘      要：AIM To evaluate the effects of glucagon-like peptide-1 analogs(GLP-1 a) combined with insulin on myocardial ischemiareperfusion injury in diabetic *** Type 2 diabetes mellitus(T2 DM) was induced in maleWistar rats with streptozotocin(65 mg/kg) and verified using an oral glucose tolerance test. After anesthesia, the left coronary artery was occluded for 40 min followed by 80 min reperfusion. Blood glucose level was measured during surgery. Rats were randomized into six groups as follows:(1) control rats;(2) insulin(0.1 U/kg) treated rats prior to ischemia;(3) insulin(0.1 U/kg) treated rats at reperfusion;(4) GLP-1 a(140 mg/kg) treated rats prior to ischemia;(5) GLP-1 a(140 mg/kg) treated rats at reperfusion; and(6) rats treated with GLP-1 a(140 mg/kg) prior to ischemia plus insulin(0.1 U/kg) at reperfusion. Myocardial area at risk and infarct size was measured planimetrically using Evans blue and triphenyltetrazolium chloride staining, *** There was no significant difference in the myocardial area at risk among groups. Insulin treatment before ischemia resulted in a significant increase in infarct size(34.7% ± 3.4% vs 18.6% ± 3.1% in the control rats, P 0.05). Post-ischemic administration of insulin or GLP-1 a had no effect on infarct size. However, pre-ischemic administration of GLP-1 a reduced infarct size to 12% ± 2.2%(P 0.05). The maximal infarct size reduction was observed in the group treated with GLP-1 a prior to ischemia and insulin at reperfusion(8% ± 1.6%, P 0.05 vs the control and GLP-1 a alone treated groups).CONCLUSION GLP-1 a pre-administration results in myocardial infarct size reduction in rats with T2 DM. These effects are maximal in rats treated with GLP-1 a pre-ischemia plus insulin at reperfusion.