Myocardial GLP-1 Receptor Activation in the Presence of Glucose: Strong Partners

Glucagon-like peptide 1 (GLP-1) receptor agonists increase the intracellular calcium levels of atrial cardiomyocytes in a protein kinase A dependent manner. This elicits a positive inotropic effect. Furthermore, the translocation of GLUT1 is promoted. The relevance of the latter process is unclear, therefore we assessed the influence of energy substrates. Muscle strips (trabeculae; n = 86) were isolated from human right atrial appendages obtained from patients undergoing heart surgery (n = 34), mounted on hooks, electrically stimulated (1 Hz) and treated with a single dose of exenatide (15 nM), GLP-1(7–36) amide (180 nM), GLP-1(9–36) amide (200 nM), isoproterenol (100 nM), or increasing concentrations of calcium (4.0 and 7.2 mM). Either 11.2 mM glucose or 22.4 mM pyruvate served as the energy substrate. Developed force, diastolic tension and relaxation parameters were recorded and analyzed. Administration of exenatide and GLP-1(7–36) amide, but not GLP-1(9–36) amide, led to a transient positive inotropic effect in the presence of pyruvate and glucose. This effect tended to be more pronounced in glucose-treated muscle strips at maximal developed force and steady state conditions. Both isoproterenol and calcium exerted a strong positive inotropic effect with no difference regarding the energy substrate. In conclusion, the positive inotropic effect of GLP-1 receptor agonists is more pronounced in glucose enriched Tyrode’s solution, which might be linked to the previously reported translocation of GLUT1.