glucagon-like-peptide-1-(7-36) and Heart-Failure

Heart failure with preserved ejection fraction (HFpEF) has emerged as a public health burden with currently no effective medication. We assessed the treatment effects of the incretin hormone glucagon-like peptide-1 (GLP-1) on cardiac metabolism and function in a model of HFpEF. Following aortic banding, rats developed HFpEF characterized by diastolic dysfunction, pulmonary congestion, and poor survival (38%). A 4-week GLP-1 treatment via osmotic pumps significantly improved survival (70%) and reduced left ventricular stiffness, diastolic dysfunction, and pulmonary congestion. Isolated heart perfusion revealed preserved cardiac glucose oxidation (GO) and a shift in cardiac substrate utilization towards GO. While GLP-1 may boost insulin secretion and responsiveness, the protective effects were not related to cardiac insulin action. GLP-1 improves diastolic function and survival in rats with HFpEF, which was associated with a cardiac substrate switch towards GO. The therapeutic role of GLP-1 in HFpEF is new and warrants further investigation.

Topics: Animals; Cardiotonic Agents; Diastole; Disease Models, Animal; Energy Metabolism; Glucagon-Like Peptide 1; Glucose; Heart Failure; Isolated Heart Preparation; Male; Myocardium; Oxidation-Reduction; Peptide Fragments; Pulmonary Edema; Rats, Sprague-Dawley; Recovery of Function; Stroke Volume; Ventricular Function, Left