title: Effects and mechanism of glucagon-like peptide-1 on injury of rats cardiomyocytes induced by hypoxia-reoxygenation.
abstract: BACKGROUND
  Although the insulinotropic role of glucagon-like peptide-1 (GLP-1) in type 2 diabetes mellitus has been substantiated, its role in cardioprotection remains largely unknown. This study aimed to determine the effects of GLP-1 on injury of rats cardiac myocytes induced by hypoxia-reoxygenation (H/R) and the possible mechanisms.
  
  
  METHODS
  The cultured neonatal rats cardiac myocytes were randomly divided into seven groups: the normal control group, the H/R group, the GLP-1 + H/R group, the GLP-1 + H/R + UO126 (the p42/44 mitogen-activated protein kinase (MAPK) inhibitor) group, the GLP-1 + H/R + LY294002 (phosphatidylinositol 3-kinase (PI3K) inhibitor) group, the H/R + UO126 group, and the H/R + LY294002 group. The lactate dehydrogenase (LDH) activity, apoptosis rate of cardiac myocytes, and caspase-3 activity were detected after the injury of H/R.
  
  
  RESULTS
  Compared with the normal control group, the activity of LDH, cardiac myocyte apoptosis rate, and caspase-3 activity all increased significantly in the H/R group (P < 0.01). Compared with the H/R group, these three indices all decreased in the H/R + GLP-1 group (P < 0.01). However, the changes of LDH activity, apoptosis rate, and caspase-3 activity were inhibited by LY294002 and UO126 respectively.
  
  
  CONCLUSIONS
  GLP-1 can directly act on cardiac myocytes and protect them from H/R injury mainly by inhibiting their apoptosis. Its mechanism may be through the PI3K-Akt pathway and the MAPK signaling pathway.
authors.affiliation: Department of Diabetic Neurology, Metabolic Disease Hospital, Tianjin Medical University, Tianjin 300070, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Xie
authors.forename: Shao-xin
authors.initials: SX
authors.lastname: Wang
authors.forename: Wei-wei
authors.initials: WW
authors.lastname: Sha
authors.forename: Xue
authors.initials: X
authors.lastname: Zhou
authors.forename: Wei-lin
authors.initials: WL
authors.lastname: Wang
authors.forename: Li-pin
authors.initials: LP
authors.lastname: Han
authors.forename: Dai-qing
authors.initials: DQ
authors.lastname: Li
authors.forename: De-min
authors.initials: DM
authors.lastname: Yu
mesh_terms: D000199:Actins / Q000032:analysis; D000818:Animals; D002070:Butadienes / Q000494:pharmacology; D015687:Cell Hypoxia; D002478:Cells, Cultured; D002867:Chromones / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000502:physiology; D052216:Glucagon-Like Peptide 1 / Q000494:pharmacology*; D020935:MAP Kinase Signaling System; D009025:Morpholines / Q000494:pharmacology; D032383:Myocytes, Cardiac / Q000187:drug effects*; D009570:Nitriles / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000199:Actins; D002070:Butadienes; D002867:Chromones; D009025:Morpholines; D009570:Nitriles; C113580:U 0126; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D052216:Glucagon-Like Peptide 1; D019869:Phosphatidylinositol 3-Kinases; D048049:Extracellular Signal-Regulated MAP Kinases