Cloning, functional expression, and chromosomal localization of the human pancreatic islet glucose-dependent insulinotropic polypeptide receptor.

Details

Serval ID
serval:BIB_D5A0E431FFA8
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Cloning, functional expression, and chromosomal localization of the human pancreatic islet glucose-dependent insulinotropic polypeptide receptor.
Journal
Diabetes
Author(s)
Gremlich S., Porret A., Hani E.H., Cherif D., Vionnet N., Froguel P., Thorens B.
ISSN
0012-1797[print], 0012-1797[linking]
Publication state
Published
Issued date
10/1995
Volume
44
Number
10
Pages
1202-1208
Language
english
Notes
Publication types: Comparative Study ; Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
Glucose-dependent insulinotropic polypeptide (GIP) is a hormone secreted by the endocrine K-cells from the duodenum that stimulates glucose-induced insulin secretion. Here, we present the molecular characterization of the human pancreatic islet GIP receptor. cDNA clones for the GIP receptor were isolated from a human pancreatic islet cDNA library. They encoded two different forms of the receptor, which differed by a 27-amino acid insertion in the COOH-terminal cytoplasmic tail. The receptor protein sequence was 81% identical to that of the rat GIP receptor. When expressed in Chinese hamster lung fibroblasts, both forms of the receptor displayed high-affinity binding for GIP (180 and 600 pmol/l). GIP binding was displaced by < 20% by 1 mumol/l glucagon, glucagon-like peptide (GLP-I)(7-36) amide, vasoactive intestinal peptide, and secretin. However exendin-4 and exendin-(9-39) at 1 mumol/l displaced binding by approximately 70 and approximately 100% at 10 mumol/l. GIP binding to both forms of the receptor induced a dose-dependent increase in intracellular cAMP levels (EC50 values of 0.6-0.8 nmol/l) but no elevation of cytoplasmic calcium concentrations. Interestingly, both exendin-4 and exendin-(9-39) were antagonists of the receptor, inhibiting GIP-induced cAMP formation by up to 60% when present at a concentration of 10 mumol/l. Finally, the physical and genetic chromosomal localization of the receptor gene was determined to be on 19q13.3, close to the ApoC2 gene. These data will help study the physiology and pathophysiology of the human GIP receptor.
Keywords
Amino Acid Sequence, Animals, Apolipoprotein C-II, Apolipoproteins C/genetics, Calcium/metabolism, Chromosome Mapping, Chromosomes, Human, Pair 19, Cloning, Molecular, Cyclic AMP/metabolism, Deoxyribonucleases, Type II Site-Specific, Gastric Inhibitory Polypeptide/metabolism, Gene Expression, Gene Library, Glucose/pharmacology, Humans, In Situ Hybridization, Fluorescence, Islets of Langerhans/metabolism, Kinetics, Linkage (Genetics), Molecular Sequence Data, Polymorphism, Restriction Fragment Length, Rats, Receptors, Gastrointestinal Hormone/biosynthesis, Receptors, Gastrointestinal Hormone/drug effects, Restriction Mapping, Sequence Homology, Amino Acid
Pubmed
Web of science
Create date
24/01/2008 13:41
Last modification date
20/08/2019 15:55
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