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.


Autoria(s): Thorens B.; Porret A.; Bühler L.; Deng S.P.; Morel P.; Widmann C.
Data(s)

01/11/1993

Resumo

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.

Identificador

http://serval.unil.ch/?id=serval:BIB_C535A2E206FC

isbn:0012-1797[print], 0012-1797[linking]

pmid:8405712

doi:10.2337/diabetes.42.11.1678

isiid:A1993MD14600020

Idioma(s)

en

Fonte

Diabetes, vol. 42, no. 11, pp. 1678-1682

Palavras-Chave #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 & inhibitors; Receptors, Cell Surface/genetics; Receptors, Glucagon; Venoms
Tipo

info:eu-repo/semantics/article

article