Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Kolesnik, E; Krainer, T; Wallner, M; Djalinac, N; Verheyen, N; Ablasser, K; Eaton, DM; Rainer, PP; Pelzmann, B; von Lewinski, D.
Myocardial GLP-1 Receptor Activation in the Presence of Glucose: Strong Partners
INT J PEPT RES THER. 2019; 25(2): 605-612.
Doi: 10.1007/s10989-018-9706-9
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- Führende Autor*innen der Med Uni Graz
- Kolesnik Ewald
- Co-Autor*innen der Med Uni Graz
- Ablasser Klemens
- Dalinac Natasa
- Pelzmann Brigitte
- Rainer Peter
- Verheyen Nicolas Dominik
- von Lewinski Dirk
- Wallner Markus
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- Abstract:
- 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 (1Hz) and treated with a single dose of exenatide (15nM), GLP-1(7-36) amide (180nM), GLP-1(9-36) amide (200nM), isoproterenol (100nM), or increasing concentrations of calcium (4.0 and 7.2mM). Either 11.2mM glucose or 22.4mM 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.
- Find related publications in this database (Keywords)
- Glucagon-like peptide 1
- Incretin mimetics
- Anti-diabetic drugs
- Atrial contractility
- GLUT1