title: Insulin inhibits myocardial ischemia-induced apoptosis and alleviates chronic adverse changes in post-ischemic cardiac structure and function.
abstract: Insulin has been shown to possess significant anti-apoptotic effect in myocardial ischemia/reperfusion (MI/R). However, the contribution by this protection of insulin to the prolonged cardiac function in rats subjected to ischemia remains unclear. The present study attempted to test whether early insulin treatment influences adverse prolonged post-ischemic cardiac structural and functional changes. Adult male rats were subjected to left anterior descending coronary artery occlusion and were randomized to receive one of the following treatments: saline (4 ml/kg/h i.v. injection beginning 10 min before the ischemia and continuing for 2 h), insulin (60 U/l, i.v. injection following the same routine, and hypodermic injection of insulin (0.5 U/ml, 1 ml/kg/d) for 3 days after the ischemia surgery) or insulin plus wortmannin (15 mug/kg i.v. injection 15 min before each insulin administration). Treatment with insulin significantly reduced infarct size, decreased plasma creatine kinase and lactate dehydrogenase activities, decreased apoptosis index and caspase-3 activity (all P < 0.01 vs. saline), and improved cardiac function 24 h after ischemia. Importantly, at the end of 4 weeks after the ischemia surgery, MI rats receiving insulin treatment showed smaller left ventricle (LV) cavity and thicker systolic interventricular septum, and increased cardiac ejection fraction and LV fractional shortening (all P < 0.05 vs. saline). Inhibition of insulin signaling with wortmannin not only blocked insulin's anti-apoptotic effect, but also almost completely abolished effects of insulin on cardiac structure and function. These data indicate that inhibition of apoptosis by early insulin treatment alleviates chronic adverse changes in post-ischemic cardiac structure and function.
authors: Department of Physiology, Xijing Hospital, Fourth Military Medical University, 710032, Xi'an, China.
authors: Wenjuan
authors: W
authors: Xing
authors: Wenjun
authors: W
authors: Yan
authors: Feng
authors: F
authors: Fu
authors: Yulan
authors: Y
authors: Jin
authors: Lele
authors: L
authors: Ji
authors: Wenchong
authors: W
authors: Liu
authors: Li
authors: L
authors: Wang
authors: Anlin
authors: A
authors: Lv
authors: Yunyan
authors: Y
authors: Duan
authors: Jun
authors: J
authors: Zhang
authors: Haifeng
authors: H
authors: Zhang
authors: Feng
authors: F
authors: Gao
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D003402:Creatine Kinase / Q000097:blood; D006334:Heart Function Tests; D007328:Insulin / Q000494:pharmacology*; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008297:Male; D009203:Myocardial Infarction / Q000097:blood / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology; D017202:Myocardial Ischemia / Q000097:blood / Q000201:enzymology / Q000473:pathology* / Q000503:physiopathology*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000473:pathology; D009569:Nitric Oxide / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D016277:Ventricular Function, Left / Q000187:drug effects
chemical_list: D007328:Insulin; D009569:Nitric Oxide; D007770:L-Lactate Dehydrogenase; D052250:Nitric Oxide Synthase Type III; D051057:Proto-Oncogene Proteins c-akt; D003402:Creatine Kinase