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Diabetes 56:143-151, 2007
DOI: 10.2337/db05-0996
© 2007 by the American Diabetes Association
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Exendin-4 Potently Decreases Ghrelin Levels in Fasting Rats

Diego Pérez-Tilve1, Lucas González-Matías1, Mayte Alvarez-Crespo1, Roberto Leiras1, Sulay Tovar2, Carlos Diéguez2, and Federico Mallo1

1 Department of Functional Biology and Health Sciences, Faculty of Biology, Laboratory of Endocrinology, University of Vigo, Vigo, Spain
2 Department of Physiology, Faculty of Medicine, University of Santiago de Compostela, Santiago de Compostela, Spain

Address correspondence and reprint requests to Federico Mallo, PhD, Faculty of Biology, Laboratory of Endocrinology, Campus of Vigo, As Lagoas–Marcosende, University of Vigo, E-36310 Vigo, Spain. E-mail: fmallo{at}uvigo.es

Abbreviations: DPP-IV, dipeptidyl peptidase-IV; Ex, exendin; GLP, glucagon-like peptide; GLP-1r, GLP-1 receptor; PWS, Prader-Willi Syndrome; RIA, radioiummunoassay

Ghrelin is a potent orexigenic and adipogenic hormone that strongly influences fat deposition and the generation of hunger in obesity. Indeed, hyperghrelinemia appears to promote an increase in food intake as seen in Prader-Willi Syndrome (PWS). Exendin (Ex)-4 is an agonist of the glucagon-like peptide (GLP)-1 receptor (GLP-1r) that has anorexigenic and fat-reducing properties. Here, we report that Ex-4 reduces the levels of ghrelin by up to 74% in fasted rats. These effects are dose dependent and long lasting (up to 8 h), and they can be detected after both central and peripheral administration of Ex-4. Suppression of ghrelin was neither mimicked by GLP-1(7–36)-NH2 nor blocked by the GLP-1r antagonist Ex-(9–39). Moreover, it was independent of the levels of leptin and insulin. The decrease in ghrelin levels induced by Ex-4 may explain the reduced food intake in fasted rats, justifying the more potent anorexigenic effects of Ex-4 when compared with GLP-1. As well as the potential benefits of Ex-4 in type 2 diabetes, the potent effects of Ex-4 on ghrelin make it tempting to speculate that Ex-4 could offer a therapeutic option for PWS and other syndromes characterized by substantial amounts of circulating ghrelin.


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Copyright © 2007 by the American Diabetes Association.