Effects and mechanism of glucagon-like peptide-1 on injury of rats cardiomyocytes induced by hypoxia-reoxygenation.
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.
Xie
Yun
Y
Department of Diabetic Neurology, Metabolic Disease Hospital, Tianjin Medical University, Tianjin 300070, China.
Wang
Shao-xin
SX
Sha
Wei-wei
WW
Zhou
Xue
X
Wang
Wei-lin
WL
Han
Li-pin
LP
Li
Dai-qing
DQ
Yu
De-min
DM
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
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