The role of incretins in cardiovascular control.
Glucagon-like peptide-1 (GLP-1) is an incretin secreted in response to nutrient ingestion. Understanding the incretin effect on diabetes pathophysiology has led to development of a new class of agents termed incretin mimetics. Exenatide is the first GLP-1 agonist approved to treat type 2 diabetes mellitus (T2DM). Clinical studies have demonstrated exenatide's efficacy in improving glycemic control, often coupled with weight loss. Studies are investigating the potential cardiovascular benefits of GLP-1 agonists. Blood pressure, cholesterol levels, C-reactive protein, and insulin resistance may improve in patients treated with exenatide. The direct effect of GLP-1 on cardiac myocytes and vascular smooth muscle has been an active area of investigation. Infusions of GLP-1 in animal models and human subjects with heart failure have demonstrated significantly improved cardia parameters. In patients with T2DM, GLP-1 infusion has been shown to improve endothelial function, irrespective of changes in insulin sensitivity. These pilot studies provide a foundation for developing therapies aimed at modulating incretin physiology for the additional benefit on the cardiovascular system in patients with T2DM and heart disease.
Mafong
Derek D
DD
University of California, San Diego School of Medicine; Veterans Affairs Medical Center, 3350 La Jolla Village Drive, San Diego, CA 92161, USA.
Henry
Robert R
RR
D002317:Cardiovascular Agents / Q000494:pharmacology*; D002319:Cardiovascular System / Q000187:drug effects* / Q000503:physiopathology; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology*; D000077270:Exenatide; D006801:Humans; D054795:Incretins / Q000502:physiology*; D010455:Peptides / Q000494:pharmacology*; D014688:Venoms / Q000494:pharmacology*
D002317:Cardiovascular Agents; D054795:Incretins; D010455:Peptides; D014688:Venoms; D000077270:Exenatide