Journal article
The Recombinant Rat Glucagon-Like Peptide-1 Receptor, Expressed in an α-Cell Line, Is Coupled to Adenylyl Cyclase Activation and Intracellular Calcium Release
Experimental and clinical endocrinology & diabetes, Vol.113(3), pp.182-189
2005
DOI: 10.1055/s-2005-837526
PMID: 15789279
Abstract
The glucagon-like peptide-1 (GLP-1) receptor is expressed on α-cells, though its functional significance is unknown. The endogenous β-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 α-cells are poorly understood. To determine the signaling mechanisms of the α-cell GLP-1 receptor, we established a stable pancreatic islet α-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 β-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 α-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 β-cells. Finally this study describes a cell line that can be used as a model system for evaluation of GLP-1 signaling in α-cells.
Details
- Title: Subtitle
- The Recombinant Rat Glucagon-Like Peptide-1 Receptor, Expressed in an α-Cell Line, Is Coupled to Adenylyl Cyclase Activation and Intracellular Calcium Release
- Creators
- J. S Dillon - Division of Endocrinology, Department of Internal Medicine, University of Iowa, Iowa City, IA, USAM Lu - Department of Ophthalmology, Children's Hospital, Harvard Medical School, Boston, MA, USAS Bowen - Division of Endocrinology, Department of Internal Medicine, University of Iowa, Iowa City, IA, USAL. L Homan - Division of Endocrinology, Department of Internal Medicine, University of Iowa, Iowa City, IA, USA
- Resource Type
- Journal article
- Publication Details
- Experimental and clinical endocrinology & diabetes, Vol.113(3), pp.182-189
- DOI
- 10.1055/s-2005-837526
- PMID
- 15789279
- ISSN
- 0947-7349
- eISSN
- 1439-3646
- Language
- English
- Date published
- 2005
- Academic Unit
- Fraternal Order of Eagles Diabetes Research Center; Endocrinology and Metabolism; Internal Medicine
- Record Identifier
- 9984094491802771
Metrics
15 Record Views