Exendin-(9-39) is an inverse agonist of the murine glucagon-like peptide-1 receptor: implications for basal intracellular cyclic adenosine 3',5'-monophosphate levels and beta-cell glucose competence.

Détails

ID Serval
serval:BIB_420668C37F5B
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Exendin-(9-39) is an inverse agonist of the murine glucagon-like peptide-1 receptor: implications for basal intracellular cyclic adenosine 3',5'-monophosphate levels and beta-cell glucose competence.
Périodique
Endocrinology
Auteur(s)
Serre V., Dolci W., Schaerer E., Scrocchi L., Drucker D., Efrat S., Thorens B.
ISSN
0013-7227
Statut éditorial
Publié
Date de publication
11/1998
Peer-reviewed
Oui
Volume
139
Numéro
11
Pages
4448-4454
Langue
anglais
Résumé
The effect of exendin-(9-39), a described antagonist of the glucagon-like peptide-1 (GLP-1) receptor, was evaluated on the formation of cAMP- and glucose-stimulated insulin secretion (GSIS) by the conditionally immortalized murine betaTC-Tet cells. These cells have a basal intracellular cAMP level that can be increased by GLP-1 with an EC50 of approximately 1 nM and can be decreased dose dependently by exendin-(9-39). This latter effect was receptor dependent, as a beta-cell line not expressing the GLP-1 receptor was not affected by exendin-(9-39). It was also not due to the endogenous production of GLP-1, because this effect was observed in the absence of detectable preproglucagon messenger RNA levels and radioimmunoassayable GLP-1. Importantly, GSIS was shown to be sensitive to this basal level of cAMP, as perifusion of betaTC-Tet cells in the presence of exendin-(9-39) strongly reduced insulin secretion. This reduction of GSIS, however, was observed only with growth-arrested, not proliferating, betaTC-Tet cells; it was also seen with nontransformed mouse beta-cells perifused in similar conditions. These data therefore demonstrated that 1) exendin-(9-39) is an inverse agonist of the murine GLP-1 receptor; 2) the decreased basal cAMP levels induced by this peptide inhibit the secretory response of betaTC-Tet cells and mouse pancreatic islets to glucose; 3) as this effect was observed only with growth-arrested cells, this indicates that the mechanism by which cAMP leads to potentiation of insulin secretion is different in proliferating and growth-arrested cells; and 4) the presence of the GLP-1 receptor, even in the absence of bound peptide, is important for maintaining elevated intracellular cAMP levels and, therefore, the glucose competence of the beta-cells.
Mots-clé
Animals, Blotting, Northern, Cell Line, Cyclic AMP, Glucagon, Glucagon-Like Peptide 1, Glucose, Islets of Langerhans, Ligands, Mice, Peptide Fragments, Proglucagon, Protein Precursors, RNA, Receptors, Glucagon
Pubmed
Web of science
Open Access
Oui
Création de la notice
24/01/2008 14:41
Dernière modification de la notice
20/08/2019 14:43
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