Insulin treatment significantly reduced I/R-induced mortality from 64.5% to 33.3% in diabetic rats by improving cardiac contractile function and partially restoring Akt/GLUT4 signaling.
Does insulin treatment improve cardiac contractile dysfunction and reduce mortality in STZ-diabetic rats subjected to myocardial ischemia-reperfusion injury?
Insulin treatment partially restores cardiac contractile function and significantly reduces I/R-induced mortality in diabetic rats, likely by improving impaired Akt/GLUT4 signaling.
Absolute Event Rate: 33.3% vs 64.5%
p-value: p=<0.05
In this study, we established systemic in-vivo evidence from molecular to organism level to explain how diabetes can aggravate myocardial ischemia-reperfusion (I/R) injury and revealed the role of insulin signaling (with specific focus on Akt/GLUT4 signaling molecules). The myocardial I/R injury was induced by the left main coronary artery occlusion for 1 hr and then 3 hr reperfusion in control, streptozotocin (STZ)-induced insulinopenic diabetes, and insulin-treated diabetic rats. The diabetic rats showed a significant decrease in heart rate, and a prolonged isovolumic relaxation (tau) which lead to decrease in cardiac output (CO) without changing total peripheral resistance (TPR). The phosphorylated Akt and glucose transporter 4 (GLUT 4) protein levels were dramatically reduced in both I/R and non-I/R diabetic rat hearts. Insulin treatment in diabetes showed improvement of contractile function as well as partially increased Akt phosphorylation and GLUT 4 protein levels. In the animals subjected to I/R, the mortality rates were 25%, 65%, and 33% in the control, diabetic, and insulin-treated diabetic group respectively. The I/R-induced arrhythmias and myocardial infarction did not differ significantly between the control and the diabetic groups. Consistent with its anti-hyperglycemic effects, insulin significantly reduced I/R-induced arrhythmias but had no effect on I/R-induced infarctions. Diabetic rat with I/R exhibited the worse hemodynamic outcome, which included systolic and diastolic dysfunctions. Insulin treatment only partially improved diastolic functions and elevated P-Akt and GLUT 4 protein levels. Our results indicate that cardiac contractile dysfunction caused by a defect in insulin-stimulated Akt/GLUT4 may be a major reason for the high mortality rate in I/R injured diabetic rats.
Huang et al. (Tue,) conducted a other in STZ-induced diabetes and myocardial ischemia-reperfusion injury (n=70). Insulin vs. Untreated STZ-induced diabetes was evaluated on I/R-induced mortality rate (p=<0.05). Insulin treatment significantly reduced I/R-induced mortality from 64.5% to 33.3% in diabetic rats by improving cardiac contractile function and partially restoring Akt/GLUT4 signaling.