Liraglutide Preserves Intracellular Calcium Handling in Isolated Murine Myocytes Exposed to Oxidative Stress

Abstract

In ischemic/reperfusion (I/R) injured hearts, severe oxidative stress occurs and is associated with intracellular calcium (Ca2+) overload. Glucagon-Like Peptide-1 (GLP-1) analogues have been shown to exert cardioprotection in I/R heart. However, there is little information regarding the effects of GLP-1 analogue on the intracellular Ca2+ regulation in the presence of oxidative stress. Therefore, we investigated the effects of GLP-1 analogue, (liraglutide, 10 µM) applied before or after hydrogen peroxide (H2O2, 50 µM) treatment on intracellular Ca2+ regulation in isolated cardiomyocytes. We hypothesized that liraglutide can attenuate intracellular Ca2+ overload in cardiomyocytes under H2O2-induced cardiomyocyte injury. Cardiomyocytes were isolated from the hearts of male Wistar rats. Isolated cardiomyocytes were loaded with Fura-2/AM and fluorescence intensity was recorded. Intracellular Ca2+ transient decay rate, intracellular Ca2+ transient amplitude and intracellular diastolic Ca2+ levels were recorded before and after treatment with liraglutide. In H2O2 induced severe oxidative stressed cardiomyocytes (which mimic cardiac I/R) injury, liraglutide given prior to or after H2O2 administration effectively increased both intracellular Ca2+ transient amplitude and intracellular Ca2+ transient decay rate, without altering the intracellular diastolic Ca2+ level. Liraglutide attenuated intracellular Ca2+ overload in H2O2-induced cardiomyocyte injury and may be responsible for cardioprotection during cardiac I/R injury by preserving physiological levels of calcium handling during the systolic and diastolic phases of myocyte activation.