Background: It is reported that glucagon-like peptide-1 (GLP-1) has direct cardioprotective effects. We hypothesise that Exenatide, a long half-life analog of GLP-1, might protect the heart against ischaemia/reperfusion (I/R) injury. In this study, the role and mechanism of Exenatide in I/R was investigated.
Methods: Two p38 mitogen-activated protein kinase (MAPK) isoforms p38α or p38γ, were knocked down by recombinant adeno-associated virus (rAAV) in male Sprague-Dawley rats. Then, rats were randomly treated with Exenatide or phosphate buffered saline (PBS) before I/R. Left ventricular function was measured. The translocation of glucose transporter 4 (GLUT4), GLUT1 and fatty acid transporter (FAT)/CD36 was assessed.
Results: Exenatide treatment increased the p38γ expression, but not p38α, in I/R rats. Exenatide significantly improved post-ischaemic cardiac function of I/R rats. The administration of Exenatide stimulated the translocation of GLUT4 and GLUT1, while it also increased the GLUT1 expression in the cytoplasm. Meanwhile, it reduced the translocation of FAT/CD36 (p<0.05). However, cardiac down-regulation of p38γ mediated by rAAV abolished not only the Exenatide-induced cardioprotective effects but also the GLUT4, GLUT1 and FAT/CD36 translocation.
Conclusions: These results demonstrated that Exenatide improved cardiac function, increased translocation of GLUTs, and suppressed translocation of FAT/CD36 after myocardial I/R injury. This protective effect was mediated, at least in part, through modulation of the cardiac p38γ MAPK.
Keywords: Exenatide; FAT/CD36.; Glucose transport proteins (GLUTs); Ischaemia/reperfusion injury; p38 mitogen-activated protein kinases (MAPK).
Copyright © 2016 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.