title: Exenatide Regulates Substrate Preferences Through the p38γ MAPK Pathway After Ischaemia/Reperfusion Injury in a Rat Heart.
abstract: 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.
authors: Department of Cardiology, the First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, P.R. China.
authors: Aihua
authors: A
authors: Zheng
authors: Department of Cardiology, the First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, P.R. China.
authors: Li
authors: L
authors: Cao
authors: Department of Cardiology, the First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, P.R. China.
authors: Shu
authors: S
authors: Qin
authors: Department of Nuclear Medicine, the Affiliated Hospital of Luzhou Medical College, Luzhou 646000, P.R.China.
authors: Yue
authors: Y
authors: Chen
authors: Department of Basic Sciences, Center for Perinatal Biology, Division of Pharmacology, Loma Linda University School of Medicine, Loma Linda, CA, USA.
authors: Yong
authors: Y
authors: Li
authors: Department of Cardiology, the First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, P.R. China. Electronic address: zhangdongyingchina@tom.com.
authors: Dongying
authors: D
authors: Zhang
mesh_terms: D000818:Animals; D015820:Cadherins / Q000378:metabolism; D002316:Cardiotonic Agents / Q000494:pharmacology*; D000077270:Exenatide; D051272:Glucose Transporter Type 1 / Q000378:metabolism; D051275:Glucose Transporter Type 4 / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008297:Male; D048291:Mitogen-Activated Protein Kinase 12 / Q000378:metabolism*; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy / Q000201:enzymology* / Q000503:physiopathology; D009206:Myocardium / Q000201:enzymology*; D010455:Peptides / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014688:Venoms / Q000494:pharmacology*; D016277:Ventricular Function, Left / Q000187:drug effects
chemical_list: D015820:Cadherins; D002316:Cardiotonic Agents; C502405:Fat1 protein, rat; D051272:Glucose Transporter Type 1; D051275:Glucose Transporter Type 4; D010455:Peptides; C495694:Slc2a4 protein, rat; D014688:Venoms; D000077270:Exenatide; D048291:Mitogen-Activated Protein Kinase 12
keywords: Exenatide; FAT/CD36.; Glucose transport proteins (GLUTs); Ischaemia/reperfusion injury; p38 mitogen-activated protein kinases (MAPK)