Cardiovascular and hemodynamic effects of glucagon-like peptide-1

Abstract

Glucagon-like peptide-1 (GLP-1) is an incretin hormone that has been shown to have hemodynamic and cardioprotective capacity in addition to its better characterized glucoregulatory actions. Because of this, emerging research has focused on the ability of GLP-1 based therapies to drive myocardial substrate selection, enhance cardiac performance and regulate heart rate, blood pressure and vascular tone. These studies have produced consistent and reproducible results amongst numerous laboratories. However, there are obvious disparities in findings obtained in small animal models versus those of higher mammals. This species dependent discrepancy calls to question, the translational value of individual findings. Moreover, few studies of GLP-1 mediated cardiovascular action have been performed in the presence of a pre-existing comorbidities (e.g. obesity/diabetes) which limits interpretation of the effectiveness of incretin-based therapies in the setting of disease. This review addresses cardiovascular and hemodynamic potential of GLP-1 based therapies with attention to species specific effects as well as the interaction between therapies and disease.

Figure 1

A graphical representation of putative pathways downstream from GLP-1 receptor activation in endothelial cells, vascular smooth muscle cells and cardiomyocytes. Pathways presented within this figure represent a compilation of data from multiple species.

Figure 2

A schematic summary of cardiovascular outcomes resulting from GLP-1 based therapies in rodents (left), higher mammals (center) and humans (right). Black arrows reflect physiologic responses in healthy animals whereas gray arrows indicate responses measured with in animals with concurrent cardiovascular disease.