Therapeutic Potential of Coagonists of Glucagon and GLP-1

Author(s): Vishal J. Patel, Amit A. Joharapurkar, Samadhan G. Kshirsagar, Kartikkumar N. Patel, Gaurang B. Shah, Mukul R. Jain.

Journal Name: Cardiovascular & Hematological Agents in Medicinal Chemistry

Volume 12 , Issue 2 , 2014

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Abstract:

Dual agonism of glucagon and glucagon-like peptide-1 (GLP-1) receptors reduces body weight without inducing hyperglycemia. In addition, coagonists have demonstrated lipid lowering property, which was independent of their anorectic effect. Similarly, GLP-1 modulates cardiovascular function which is favorable for treatment of myocardial injury, cardiac dysfunction, cardiac arrhythmias, endothelial dysfunction, and blood pressure, while glucagon has a positive impact on heart rate, cardiac output, ventricular contraction and enhances cardiac performance in animals and humans. Hence, researchers focused on combining these attributes of GLP-1 and glucagon in a single molecule, which was termed as a coagonist. Oxyntomodulin is the naturally occurring coagonist of GLP-1 and glucagon. This review focusses on the coagonists under clinical development discussing activities affecting cardiovascular functions, lipid modulation, direct effect on cardiac functions or other related functions. A comparative analysis of the in vitro and in vivo properties of GLP-1, glucagon and the coagonists is also carried out. This review discusses potential of GLP-1 and glucagon coagonists in treatment of cardiovascular and hemodynamic diseases with attention to GLP-1 or glucagon receptor specific properties as well as the interaction between other therapies.

Keywords: Cardiovascular effect, coagonist, GLP-1, Glucagon and oxyntomodulin.

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Article Details

VOLUME: 12
ISSUE: 2
Year: 2014
Page: [126 - 133]
Pages: 8
DOI: 10.2174/1871525712666141019194025
Price: $58

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