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 (P13K) 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 P13K-Akt pathway and the MAPK signaling pathway.