Free fatty acid receptor 4 inhibitory signaling in delta cells regulates islet hormone secretion in mice
Objective: Maintenance of glucose homeostasis requires the precise regulation of hormone secretion from the endocrine pancreas. Free fatty acid receptor 4 (FFAR4/GPR120) is a G protein-coupled receptor whose activation in islets of Langerhans promotes insulin and glucagon secretion and inhibits soma...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2021-03-01
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| Series: | Molecular Metabolism |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2212877821000065 |
| _version_ | 1831636478604607488 |
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| author | Marine L. Croze Marcus F. Flisher Arthur Guillaume Caroline Tremblay Glyn M. Noguchi Sabrina Granziera Kevin Vivot Vincent C. Castillo Scott A. Campbell Julien Ghislain Mark O. Huising Vincent Poitout |
| author_facet | Marine L. Croze Marcus F. Flisher Arthur Guillaume Caroline Tremblay Glyn M. Noguchi Sabrina Granziera Kevin Vivot Vincent C. Castillo Scott A. Campbell Julien Ghislain Mark O. Huising Vincent Poitout |
| author_sort | Marine L. Croze |
| collection | DOAJ |
| description | Objective: Maintenance of glucose homeostasis requires the precise regulation of hormone secretion from the endocrine pancreas. Free fatty acid receptor 4 (FFAR4/GPR120) is a G protein-coupled receptor whose activation in islets of Langerhans promotes insulin and glucagon secretion and inhibits somatostatin secretion. However, the contribution of individual islet cell types (α, β, and δ cells) to the insulinotropic and glucagonotropic effects of GPR120 remains unclear. As gpr120 mRNA is enriched in somatostatin-secreting δ cells, we hypothesized that GPR120 activation stimulates insulin and glucagon secretion via inhibition of somatostatin release. Methods: Glucose tolerance tests were performed in mice after administration of selective GPR120 agonist Compound A. Insulin, glucagon, and somatostatin secretion were measured in static incubations of isolated mouse islets in response to endogenous (ω-3 polyunsaturated fatty acids) and/or pharmacological (Compound A and AZ-13581837) GPR120 agonists. The effect of Compound A on hormone secretion was tested further in islets isolated from mice with global or somatostatin cell-specific knock-out of gpr120. Gpr120 expression was assessed in pancreatic sections by RNA in situ hybridization. Cyclic AMP (cAMP) and calcium dynamics in response to pharmacological GPR120 agonists were measured specifically in α, β, and δ cells in intact islets using cAMPER and GCaMP6 reporter mice, respectively. Results: Acute exposure to Compound A increased glucose tolerance, circulating insulin, and glucagon levels in vivo. Endogenous and/or pharmacological GPR120 agonists reduced somatostatin secretion in isolated islets and concomitantly demonstrated dose-dependent potentiation of glucose-stimulated insulin secretion and arginine-stimulated glucagon secretion. Gpr120 was enriched in δ cells. Pharmacological GPR120 agonists reduced cAMP and calcium levels in δ cells but increased these signals in α and β cells. Compound A-mediated inhibition of somatostatin secretion was insensitive to pertussis toxin. The effect of Compound A on hormone secretion was completely absent in islets from mice with either global or somatostatin cell-specific deletion of gpr120 and partially reduced upon blockade of somatostatin receptor signaling by cyclosomatostatin. Conclusions: Inhibitory GPR120 signaling in δ cells contributes to both insulin and glucagon secretion in part by mitigating somatostatin release. |
| first_indexed | 2024-12-19T06:33:46Z |
| format | Article |
| id | doaj.art-d4cba72dc14e46cfaebece614a2320bc |
| institution | Directory Open Access Journal |
| issn | 2212-8778 |
| language | English |
| last_indexed | 2024-12-19T06:33:46Z |
| publishDate | 2021-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Metabolism |
| spelling | doaj.art-d4cba72dc14e46cfaebece614a2320bc2022-12-21T20:32:17ZengElsevierMolecular Metabolism2212-87782021-03-0145101166Free fatty acid receptor 4 inhibitory signaling in delta cells regulates islet hormone secretion in miceMarine L. Croze0Marcus F. Flisher1Arthur Guillaume2Caroline Tremblay3Glyn M. Noguchi4Sabrina Granziera5Kevin Vivot6Vincent C. Castillo7Scott A. Campbell8Julien Ghislain9Mark O. Huising10Vincent Poitout11Montreal Diabetes Research Center, CRCHUM, Montréal, QC, CanadaDepartment of Neurobiology, Physiology, and Behavior, College of Biological Sciences, University of California Davis, Davis, CA, USAMontreal Diabetes Research Center, CRCHUM, Montréal, QC, CanadaMontreal Diabetes Research Center, CRCHUM, Montréal, QC, CanadaDepartment of Neurobiology, Physiology, and Behavior, College of Biological Sciences, University of California Davis, Davis, CA, USAMontreal Diabetes Research Center, CRCHUM, Montréal, QC, CanadaMontreal Diabetes Research Center, CRCHUM, Montréal, QC, CanadaDepartment of Neurobiology, Physiology, and Behavior, College of Biological Sciences, University of California Davis, Davis, CA, USAMontreal Diabetes Research Center, CRCHUM, Montréal, QC, CanadaMontreal Diabetes Research Center, CRCHUM, Montréal, QC, CanadaDepartment of Neurobiology, Physiology, and Behavior, College of Biological Sciences, University of California Davis, Davis, CA, USA; Department of Physiology and Membrane Biology, School of Medicine, University of California Davis, Davis, CA, USAMontreal Diabetes Research Center, CRCHUM, Montréal, QC, Canada; Department of Medicine, Université de Montréal, Montréal, QC, Canada; Corresponding author. Vincent Poitout, DVM, PhD, CRCHUM, 900 rue St Denis, Montréal, QC, H2X 0A9, Canada. Tel.: +1 (514) 890 8044.Objective: Maintenance of glucose homeostasis requires the precise regulation of hormone secretion from the endocrine pancreas. Free fatty acid receptor 4 (FFAR4/GPR120) is a G protein-coupled receptor whose activation in islets of Langerhans promotes insulin and glucagon secretion and inhibits somatostatin secretion. However, the contribution of individual islet cell types (α, β, and δ cells) to the insulinotropic and glucagonotropic effects of GPR120 remains unclear. As gpr120 mRNA is enriched in somatostatin-secreting δ cells, we hypothesized that GPR120 activation stimulates insulin and glucagon secretion via inhibition of somatostatin release. Methods: Glucose tolerance tests were performed in mice after administration of selective GPR120 agonist Compound A. Insulin, glucagon, and somatostatin secretion were measured in static incubations of isolated mouse islets in response to endogenous (ω-3 polyunsaturated fatty acids) and/or pharmacological (Compound A and AZ-13581837) GPR120 agonists. The effect of Compound A on hormone secretion was tested further in islets isolated from mice with global or somatostatin cell-specific knock-out of gpr120. Gpr120 expression was assessed in pancreatic sections by RNA in situ hybridization. Cyclic AMP (cAMP) and calcium dynamics in response to pharmacological GPR120 agonists were measured specifically in α, β, and δ cells in intact islets using cAMPER and GCaMP6 reporter mice, respectively. Results: Acute exposure to Compound A increased glucose tolerance, circulating insulin, and glucagon levels in vivo. Endogenous and/or pharmacological GPR120 agonists reduced somatostatin secretion in isolated islets and concomitantly demonstrated dose-dependent potentiation of glucose-stimulated insulin secretion and arginine-stimulated glucagon secretion. Gpr120 was enriched in δ cells. Pharmacological GPR120 agonists reduced cAMP and calcium levels in δ cells but increased these signals in α and β cells. Compound A-mediated inhibition of somatostatin secretion was insensitive to pertussis toxin. The effect of Compound A on hormone secretion was completely absent in islets from mice with either global or somatostatin cell-specific deletion of gpr120 and partially reduced upon blockade of somatostatin receptor signaling by cyclosomatostatin. Conclusions: Inhibitory GPR120 signaling in δ cells contributes to both insulin and glucagon secretion in part by mitigating somatostatin release.http://www.sciencedirect.com/science/article/pii/S2212877821000065FFAR4GPR120SomatostatinInsulinGlucagonIslet of langerhans |
| spellingShingle | Marine L. Croze Marcus F. Flisher Arthur Guillaume Caroline Tremblay Glyn M. Noguchi Sabrina Granziera Kevin Vivot Vincent C. Castillo Scott A. Campbell Julien Ghislain Mark O. Huising Vincent Poitout Free fatty acid receptor 4 inhibitory signaling in delta cells regulates islet hormone secretion in mice Molecular Metabolism FFAR4 GPR120 Somatostatin Insulin Glucagon Islet of langerhans |
| title | Free fatty acid receptor 4 inhibitory signaling in delta cells regulates islet hormone secretion in mice |
| title_full | Free fatty acid receptor 4 inhibitory signaling in delta cells regulates islet hormone secretion in mice |
| title_fullStr | Free fatty acid receptor 4 inhibitory signaling in delta cells regulates islet hormone secretion in mice |
| title_full_unstemmed | Free fatty acid receptor 4 inhibitory signaling in delta cells regulates islet hormone secretion in mice |
| title_short | Free fatty acid receptor 4 inhibitory signaling in delta cells regulates islet hormone secretion in mice |
| title_sort | free fatty acid receptor 4 inhibitory signaling in delta cells regulates islet hormone secretion in mice |
| topic | FFAR4 GPR120 Somatostatin Insulin Glucagon Islet of langerhans |
| url | http://www.sciencedirect.com/science/article/pii/S2212877821000065 |
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