Glucagon-like peptide-1 (GLP-1) analogues are likely to exert cardioprotective effects via balancing the energy metabolism in cardiomyocytes following ischemic or hypoxic insults. The present study aimed to explore the protective effects and mechanism of exendin4, a GLP1 analogue, on
cardiomyocyte glucose uptake using an in vitro model of hypoxia/reoxygenation (H/R) of H9c2 cardiomyocyte cells. Pretreatment with exendin4 (200 nM) prior to H/R increased the cell viability, decreased cell apoptosis, enhanced cardiomyocyte glucose uptake and increased the production
of adenosine triphosphate. Exendin4 also decreased the levels of lactate dehydrogenase and creatine kinaseMB in the culture medium. Furthermore, the activity of carnitine palmitoyltransferase1 in the H9c2 cells was decreased, while the activity of phosphofructokinase1 was increased following
exendin4 treatment. Moreover, pretreatment with exendin4 increased the expression of p38 mitogenactivated protein kinase (p38MAPK) γ and translocation of glucose transporter1 in H9c2 cells subjected to H/R. However, these effects were attenuated by the p38MAPK inhibitors BIRB796
and SB203580. The results suggested that exendin4 exerted significant cardioprotective effects against H/Rinduced cell injury and restored the metabolic imbalance of cardiomyocytes by activating the p38MAPK signaling pathway in the H9c2 cell model. Importantly, p38MAPKγ, one subunit
of p38MAPK, may have the most important function in this process. The results of the present study may be helpful in the development of novel drugs to treat patients with coronary heart disease.
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Document Type: Research Article
Department of Cardiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, P.R. China
Center for Perinatal Biology, Division of Pharmacology, Department of Basic Sciences, Loma Linda University School of Medicine, Loma Linda, CA 92350, USA
Publication date: August 1, 2015
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Molecular Medicine Reports is a monthly, peer-reviewed journal available in print and online, that includes studies devoted to molecular medicine, underscoring aspects including pharmacology, pathology, genetics, neurosciences, infectious diseases, molecular cardiology and molecular surgery. In vitro and in vivo studies of experimental model systems pertaining to the mechanisms of a variety of diseases offer researchers the necessary tools and knowledge with which to aid the diagnosis and treatment of human diseases.
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