Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Amino Acids / analysis
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Base Sequence
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Cloning, Molecular
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Cyclic AMP / analysis
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Cyclic AMP / metabolism
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DNA / analysis
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DNA / genetics
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Diabetes Mellitus, Type 2 / drug therapy
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Exenatide
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Gene Expression / genetics*
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Glucagon-Like Peptide-1 Receptor
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Humans
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Islets of Langerhans / chemistry
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Islets of Langerhans / metabolism
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Islets of Langerhans / ultrastructure
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Ligands
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Molecular Sequence Data
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Peptide Fragments / analysis
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Peptide Fragments / pharmacology*
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Peptides / analysis
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Peptides / pharmacology*
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Peptides / therapeutic use
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Receptors, Cell Surface* / antagonists & inhibitors
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Receptors, Cell Surface* / genetics
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Receptors, Cell Surface* / physiology
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Receptors, Glucagon*
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Venoms*
Substances
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Amino Acids
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GLP1R protein, human
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Glp1r protein, rat
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Glucagon-Like Peptide-1 Receptor
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Ligands
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Peptide Fragments
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Peptides
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Receptors, Cell Surface
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Receptors, Glucagon
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Venoms
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exendin (9-39)
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DNA
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Exenatide
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Cyclic AMP
Associated data
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GENBANK/D14315
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GENBANK/D14316
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GENBANK/D14317
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GENBANK/D14318
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GENBANK/L13313
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GENBANK/L13314
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GENBANK/L13315
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GENBANK/L13316
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GENBANK/U01104
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GENBANK/X75014