Cloning and functional expression of the human islet GLP-1 receptor. Demonstration that exendin-4 is an agonist and exendin-(9-39) an antagonist of the receptor.

Détails

ID Serval
serval:BIB_C535A2E206FC
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Cloning and functional expression of the human islet GLP-1 receptor. Demonstration that exendin-4 is an agonist and exendin-(9-39) an antagonist of the receptor.
Périodique
Diabetes
Auteur(s)
Thorens B., Porret A., Bühler L., Deng S.P., Morel P., Widmann C.
ISSN
0012-1797[print], 0012-1797[linking]
Statut éditorial
Publié
Date de publication
11/1993
Volume
42
Numéro
11
Pages
1678-1682
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
A complementary DNA for a glucagon-like peptide-1 receptor was isolated from a human pancreatic islet cDNA library. The isolated clone encoded a protein with 90% identity to the rat receptor. In stably transfected fibroblasts, the receptor bound [125I]GLP-1 with high affinity (Kd = 0.5 nM) and was coupled to adenylate cyclase as detected by a GLP-1-dependent increase in cAMP production (EC50 = 93 pM). Two peptides from the venom of the lizard Heloderma suspectum, exendin-4 and exendin-(9-39), displayed similar ligand binding affinities to the human GLP-1 receptor. Whereas exendin-4 acted as an agonist of the receptor, inducing cAMP formation, exendin-(9-39) was an antagonist of the receptor, inhibiting GLP-1-induced cAMP production. Because GLP-1 has been proposed as a potential agent for treatment of NIDDM, our present data will contribute to the characterization of the receptor binding site and the development of new agonists of this receptor.
Mots-clé
Amino Acid Sequence, Amino Acids/analysis, Base Sequence, Cloning, Molecular, Cyclic AMP/analysis, Cyclic AMP/metabolism, DNA/analysis, DNA/genetics, Diabetes Mellitus, Type 2/drug therapy, Gene Expression/genetics, Humans, Islets of Langerhans/chemistry, Islets of Langerhans/metabolism, Ligands, Molecular Sequence Data, Peptide Fragments/analysis, Peptide Fragments/pharmacology, Peptides/analysis, Peptides/pharmacology, Receptors, Cell Surface/antagonists &amp, inhibitors, Receptors, Cell Surface/genetics, Receptors, Glucagon, Venoms
Pubmed
Web of science
Création de la notice
24/01/2008 15:43
Dernière modification de la notice
03/03/2018 21:15
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