The Cardiovascular Biology of Glucagon-like Peptide-1

• Published in: Cell metabolism Vol. 24; no. 1; pp. 15 - 30
• Main Author: Drucker, Daniel J.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 12.07.2016
• Subjects: Animals; Cardiovascular System - metabolism; Clinical Trials as Topic; Glucagon-Like Peptide 1 - metabolism; Humans; Inflammation - metabolism; Inflammation - pathology; Models, Biological; Signal Transduction
• ISSN: 1550-4131; 1932-7420; 1932-7420
• DOI: 10.1016/j.cmet.2016.06.009

Glucagon-like peptide-1, produced predominantly in enteroendocrine cells, controls glucose metabolism and energy homeostasis through regulation of islet hormone secretion, gastrointestinal motility, and food intake, enabling development of GLP-1 receptor (GLP-1R) agonists for the treatment of diabetes and obesity. GLP-1 also acts on the immune system to suppress inflammation, and GLP-1R signaling in multiple tissues impacts cardiovascular function in health and disease. Here we review how GLP-1 and clinically approved GLP-1R agonists engage mechanisms that influence the risk of developing cardiovascular disease. We discuss how GLP-1R agonists modify inflammation, cardiovascular physiology, and pathophysiology in normal and diabetic animals through direct and indirect mechanisms and review human studies illustrating mechanisms linking GLP-1R signaling to modification of the cardiovascular complications of diabetes. The risks and benefits of GLP-1R agonists are updated in light of recent data suggesting that GLP-1R agonists favorably modify outcomes in diabetic subjects at high risk for cardiovascular events. GLP-1 receptor agonists are utilized for treatment of diabetes and obesity. Herein we update mechanisms linking GLP-1R signaling to control of glucose, body weight, inflammation, heart rate, blood pressure, and atherosclerosis, integrating data from preclinical and human studies that illuminate the efficacy, safety, and biology of the GLP-1 receptor system.