Cloning and functional expression of the human glucagon-like peptide-1 (GLP-1) receptor
| Autor: | Michael B. Wheeler, H. Yoo-Warren, Y. Tanizawa, Aubrey E. Boyd, Xing-Hong Leng, Joseph S. Dillon, Brooke Ligon, D. U. Rabin, M. A. Permutt |
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| Rok vydání: | 1993 |
| Předmět: |
endocrine system
medicine.medical_specialty DNA Complementary Molecular Sequence Data Receptors Cell Surface Biology Binding Competitive Second Messenger Systems Glucagon-Like Peptide-1 Receptor Endocrinology Internal medicine Cyclic AMP Receptors Glucagon medicine Enzyme-linked receptor Animals Humans Tissue Distribution 5-HT5A receptor Amino Acid Sequence Cloning Molecular Receptor Glucagon-like peptide 1 receptor Cell Line Transformed Base Sequence Parathyroid hormone receptor Liver receptor homolog-1 Intracellular Membranes Blotting Northern Molecular biology Molecular Probes Interleukin-21 receptor Calcium Estrogen-related receptor gamma hormones hormone substitutes and hormone antagonists |
| Zdroj: | Endocrinology. 133:1907-1910 |
| ISSN: | 1945-7170 0013-7227 |
| DOI: | 10.1210/endo.133.4.8404634 |
| Popis: | Truncated forms of glucagon-like peptide-1 are the most potent endogenous stimuli of insulin secretion and have powerful antidiabetogenic effects. To determine the structure and coupling mechanisms of the human GLP-1 receptor we have isolated two pancreatic islet cDNAs, encoding the 463 amino acid receptor and differing mainly in their 3' untranslated regions. The deduced amino acid sequence is 90% homologous with the rat GLP-1 receptor. Northern blot analysis shows expression of a single 2.7 kb transcript in pancreatic tissue. When expressed in COS-7 cells the recombinant receptor conferred specific, high affinity GLP-1(7-37) binding. GLP-1(7-37) increased intracellular cAMP in a concentration dependent manner and caused an increase in the free cytosolic calcium ([Ca2+]i) from an intracellular pool, characteristic of phospholipase C (PLC) activation. Thus, like the structurally related glucagon and parathyroid hormone receptors, the human GLP-1 receptor can activate multiple intracellular signaling pathways including adenylyl cyclase and PLC. Knowledge of the GLP-1 receptor structure will facilitate the development of receptor agonists and elucidation of the important role of GLP-1 in normal physiology and disease states. |
| Databáze: | OpenAIRE |
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