Apoptosis

, Volume 14, Issue 9, pp 1050–1060

Insulin inhibits myocardial ischemia-induced apoptosis and alleviates chronic adverse changes in post-ischemic cardiac structure and function

  • Wenjuan Xing
  • Wenjun Yan
  • Feng Fu
  • Yulan Jin
  • Lele Ji
  • Wenchong Liu
  • Li Wang
  • Anlin Lv
  • Yunyan Duan
  • Jun Zhang
  • Haifeng Zhang
  • Feng Gao
Original Paper

DOI: 10.1007/s10495-009-0378-y

Cite this article as:
Xing, W., Yan, W., Fu, F. et al. Apoptosis (2009) 14: 1050. doi:10.1007/s10495-009-0378-y

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 μg/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.

Keywords

InsulinApoptosisMyocardial ischemiaRemodelingCardiac function

Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • Wenjuan Xing
    • 1
    • 2
  • Wenjun Yan
    • 1
    • 2
  • Feng Fu
    • 1
    • 2
  • Yulan Jin
    • 3
  • Lele Ji
    • 1
    • 2
  • Wenchong Liu
    • 1
    • 2
  • Li Wang
    • 1
    • 2
  • Anlin Lv
    • 1
    • 2
  • Yunyan Duan
    • 4
  • Jun Zhang
    • 4
  • Haifeng Zhang
    • 1
    • 2
  • Feng Gao
    • 1
    • 2
  1. 1.Department of Physiology, Xijing HospitalFourth Military Medical UniversityXi’anChina
  2. 2.Department of Cardiology, Xijing HospitalFourth Military Medical UniversityXi’anChina
  3. 3.Department of Preventive MedicineNorth China Coal Medical CollegeTangshanChina
  4. 4.Department of Ultrasonic Diagnosis, Xijing HospitalFourth Military Medical UniversityXi’anChina