Signal transduction by the cloned glucagon-like peptide-1 receptor: comparison with signaling by the endogenous receptors of beta cell lines.

Détails

ID Serval
serval:BIB_DABDB390431F
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Signal transduction by the cloned glucagon-like peptide-1 receptor: comparison with signaling by the endogenous receptors of beta cell lines.
Périodique
Molecular Pharmacology
Auteur(s)
Widmann C., Bürki E., Dolci W., Thorens B.
ISSN
0026-895X[print], 0026-895X[linking]
Statut éditorial
Publié
Date de publication
05/1994
Volume
45
Numéro
5
Pages
1029-1035
Langue
anglais
Notes
Publication types: Comparative Study ; Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
Glucagon-like peptide-1 (GLP-1) is a gastrointestinal hormone that potentiates glucose-induced insulin secretion by pancreatic beta cells. The mechanisms of interaction between GLP-1 and glucose signaling pathways are not well understood. Here we studied the coupling of the cloned GLP-1 receptor, expressed in fibroblasts or in COS cells, to intracellular second messengers and compared this signaling with that of the endogenous receptor expressed in insulinoma cell lines. Binding of GLP-1 to the cloned receptor stimulated formation of cAMP with the same dose dependence and similar kinetics, compared with the endogenous receptor of insulinoma cells. Compared with forskolin-induced cAMP accumulation, that induced by GLP-1 proceeded with the same initial kinetics but rapidly reached a plateau, suggesting fast desensitization of the receptor. Coupling to the phospholipase C pathway was assessed by measuring inositol phosphate production and variations in the intracellular calcium concentration. No GLP-1-induced production of inositol phosphates could be measured in the different cell types studied. A rise in the intracellular calcium concentration was nevertheless observed in transfected COS cells but was much smaller than that observed in response to norepinephrine in cells also expressing the alpha 1B-adrenergic receptor. Importantly, no such increase in the intracellular calcium concentration could be observed in transfected fibroblasts or insulinoma cells, which, however, responded well to thrombin or carbachol, respectively. Together, our data show that interaction between GLP-1 and glucose signaling pathways in beta cells may be mediated uniquely by an increase in the intracellular cAMP concentration, with the consequent activation of protein kinase A and phosphorylation of elements of the glucose-sensing apparatus or of the insulin granule exocytic machinery.
Mots-clé
Animals, Calcium/metabolism, Cells, Cultured, Cloning, Molecular, Cyclic AMP/biosynthesis, Glucagon/metabolism, Glucagon-Like Peptide 1, Inositol Phosphates/biosynthesis, Islets of Langerhans/cytology, Islets of Langerhans/metabolism, Kinetics, Peptide Fragments/metabolism, Protein Precursors/metabolism, Rats, Receptors, Cell Surface/genetics, Receptors, Cell Surface/physiology, Receptors, Glucagon, Signal Transduction, Tumor Cells, Cultured
Pubmed
Web of science
Création de la notice
24/01/2008 15:43
Dernière modification de la notice
20/08/2019 16:59
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