The Recombinant Rat Glucagon-Like Peptide-1 Receptor, Expressed in an α-Cell Line, Is Coupled to Adenylyl Cyclase Activation and Intracellular Calcium Release
| Autor: | L. L. Homan, S. Bowen, M. Lu, Joseph S. Dillon |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
endocrine system
Endocrinology Diabetes and Metabolism Biology Phosphatidylinositols Glucagon-Like Peptide-1 Receptor Calcium in biology Cell Line Membrane Potentials Adenylyl cyclase Islets of Langerhans chemistry.chemical_compound Endocrinology Glucagon-Like Peptide 1 Cyclic AMP Receptors Glucagon Internal Medicine Animals Protein Precursors Receptor Glucagon-like peptide 1 receptor Cell Membrane Osmolar Concentration digestive oral and skin physiology ADCY9 Depolarization Intracellular Membranes General Medicine Glucagon Peptide Fragments Recombinant Proteins Rats Cell biology Enzyme Activation chemistry Calcium Signal transduction hormones hormone substitutes and hormone antagonists Intracellular Adenylyl Cyclases |
| Zdroj: | Experimental and Clinical Endocrinology & Diabetes. 113:182-189 |
| ISSN: | 1439-3646 0947-7349 |
| DOI: | 10.1055/s-2005-837526 |
| Popis: | The glucagon-like peptide-1 (GLP-1) receptor is expressed on alpha-cells, though its functional significance is unknown. The endogenous beta-cell GLP-1 receptor is coupled to adenylyl cyclase, cell depolarization, activation of voltage-dependent Ca2+ channels (VDCC) and extracellular Ca2+ influx (Lu et al., 1993 b). In contrast, the signaling pathways of the GLP-1 receptor in alpha-cells are poorly understood. To determine the signaling mechanisms of the alpha-cell GLP-1 receptor, we established a stable pancreatic islet alpha-cell line expressing the recombinant rat GLP-1 receptor (INR1-SF2), using INRl-G9 cells. These INRl-G9 cells do not express endogenous GLP-1 receptor. In INR1-SF2 cells, GLP-1 bound to the recombinant receptor (Kd = 0.9 nM) and increased cAMP (ED50 = 0.6 nM). GLP-1 increased the free cytosolic Ca2+ ([Ca2+]i) (ED50 = 50 nM) by release from intracellular stores, but did not affect INR1-SF2 cell phosphoinositol turnover. Despite expressing VDCC, the INR1-SF2 cells were not depolarized by GLP-1, even in the presence of glucose. This contrasts with the depolarizing action of GLP-1 in beta-cells in the presence of glucose (Lu et al., 1993 b). This study establishes that a single GLP-1 receptor species can mediate the effects of GLP-1 through multiple signaling pathways, including the adenylyl cyclase system and intracellular Ca2+ release, in an alpha-cell type. Furthermore, since GLP-1 is unable to cause cellular depolarization or activate VDCC in INR1-SF2 cells, these data suggest that glucose-induced membrane depolarization may be crucial for GLP-1 to further activate VDCC and potentiate glucose-stimulated insulin release in beta-cells. Finally this study describes a cell line that can be used as a model system for evaluation of GLP-1 signaling in alpha-cells. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|