Effects of Glucagon-Like Peptide-1 and Long-Acting Analogues on Cardiovascular and Metabolic Function

Authors: Saraceni, Christine; Broderick, Tom L.

Source: Drugs in R&D, Volume 8, Number 3, 2007 , pp. 145-153(9)

Publisher: Adis International

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Abstract:

Although the insulinotropic role of glucagon-like peptide-1 (GLP-1) in type 2 diabetes mellitus has been substantiated, its role in cardioprotection remains largely unknown. To ascertain the role of the cardiovascular actions of GLP-1 in health and disease states necessitates a review of the current evidence as well as ongoing investigation. Of cardiovascular significance, both positive inotropic and chronotropic effects, unmodifiable by β-adrenergic blockers, have been reportedly attributed to GLP-1 actions on the myocardium. However, the potent role of GLP-1 and its analogues in eliciting tachycardic and pressor effects should be of some concern. Aside from its reported insulinotropic activity, GLP-1 impacts the myocardium directly. Highly specific GLP-1 receptors have been identified in the heart and within the central nervous system, particularly in the nucleus tractus solitarius, a neuromodulatory centre of cardiovascular control. The occurrence of GLP-1 receptors in cardiac tissue and autonomic regions of cardiovascular control has stimulated investigation, particularly as these sites may be suitable targets for the pharmacological action of GLP-1 and long-acting analogues. Discordance on the haemodynamic consequences of GLP-1 pharmacotherapy in experimental animals and human patients has been reported in the literature. However, long-term pharmacological doses of GLP-1 have shown prolonged and beneficial actions on cardiovascular homeostasis in the adjuvant treatment of metabolic disease.

Keywords: Cardiovascular disorders; Glucagon like peptide 1; Insulinotropin agonists; Metabolic disorders

Document Type: Review article

Affiliations: 1: Department of Physiology, Midwestern University, Glendale, Arizona, USA

Publication date: 2007-01-01

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