Functional architecture of pancreatic islets identifies a population of first responder cells that drive the first-phase calcium response
Insulin-secreting β-cells are functionally heterogeneous. Whether there exist cells driving the first-phase calcium response in individual islets, has not been examined. We examine “first responder” cells, defined by the earliest [Ca2+] response during first-phase [Ca2+] elevation, distinct from pre...
| Main Authors: | , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
Public Library of Science
2022
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| _version_ | 1826308662344286208 |
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| author | Kravets, V Dwulet, JW Schleicher, WE Davis, AM Pyle, L Piscopio, RA Sticco-Ives, M Benninger, RKP |
| author_facet | Kravets, V Dwulet, JW Schleicher, WE Davis, AM Pyle, L Piscopio, RA Sticco-Ives, M Benninger, RKP |
| author_sort | Kravets, V |
| collection | OXFORD |
| description | Insulin-secreting β-cells are functionally heterogeneous. Whether there exist cells driving the first-phase calcium response in individual islets, has not been examined. We examine “first responder” cells, defined by the earliest [Ca2+] response during first-phase [Ca2+] elevation, distinct from previously identified “hub” and “leader” cells. We used islets isolated from Mip-CreER; Rosa-Stop-Lox-Stop-GCamP6s mice (β-GCamP6s) that show β-cell-specific GCamP6s expression following tamoxifen-induced CreER-mediated recombination. First responder cells showed characteristics of high membrane excitability and lower electrical coupling to their neighbors. The first-phase response time of β-cells in the islet was spatially organized, dependent on the cell’s distance to the first responder cell, and consistent over time up to approximately 24 h. When first responder cells were laser ablated, the first-phase [Ca2+] was slowed down, diminished, and discoordinated compared to random cell ablation. Cells that were next earliest to respond often took over the role of the first responder upon ablation. In summary, we discover and characterize a distinct first responder β-cell state, critical for the islet first-phase response to glucose. |
| first_indexed | 2024-03-07T07:22:40Z |
| format | Journal article |
| id | oxford-uuid:4c74cb1d-41c1-4251-90c3-b062d83237e8 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T07:22:40Z |
| publishDate | 2022 |
| publisher | Public Library of Science |
| record_format | dspace |
| spelling | oxford-uuid:4c74cb1d-41c1-4251-90c3-b062d83237e82022-10-25T09:55:16ZFunctional architecture of pancreatic islets identifies a population of first responder cells that drive the first-phase calcium responseJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:4c74cb1d-41c1-4251-90c3-b062d83237e8EnglishSymplectic ElementsPublic Library of Science2022Kravets, VDwulet, JWSchleicher, WEDavis, AMPyle, LPiscopio, RASticco-Ives, MBenninger, RKPInsulin-secreting β-cells are functionally heterogeneous. Whether there exist cells driving the first-phase calcium response in individual islets, has not been examined. We examine “first responder” cells, defined by the earliest [Ca2+] response during first-phase [Ca2+] elevation, distinct from previously identified “hub” and “leader” cells. We used islets isolated from Mip-CreER; Rosa-Stop-Lox-Stop-GCamP6s mice (β-GCamP6s) that show β-cell-specific GCamP6s expression following tamoxifen-induced CreER-mediated recombination. First responder cells showed characteristics of high membrane excitability and lower electrical coupling to their neighbors. The first-phase response time of β-cells in the islet was spatially organized, dependent on the cell’s distance to the first responder cell, and consistent over time up to approximately 24 h. When first responder cells were laser ablated, the first-phase [Ca2+] was slowed down, diminished, and discoordinated compared to random cell ablation. Cells that were next earliest to respond often took over the role of the first responder upon ablation. In summary, we discover and characterize a distinct first responder β-cell state, critical for the islet first-phase response to glucose. |
| spellingShingle | Kravets, V Dwulet, JW Schleicher, WE Davis, AM Pyle, L Piscopio, RA Sticco-Ives, M Benninger, RKP Functional architecture of pancreatic islets identifies a population of first responder cells that drive the first-phase calcium response |
| title | Functional architecture of pancreatic islets identifies a population of first responder cells that drive the first-phase calcium response |
| title_full | Functional architecture of pancreatic islets identifies a population of first responder cells that drive the first-phase calcium response |
| title_fullStr | Functional architecture of pancreatic islets identifies a population of first responder cells that drive the first-phase calcium response |
| title_full_unstemmed | Functional architecture of pancreatic islets identifies a population of first responder cells that drive the first-phase calcium response |
| title_short | Functional architecture of pancreatic islets identifies a population of first responder cells that drive the first-phase calcium response |
| title_sort | functional architecture of pancreatic islets identifies a population of first responder cells that drive the first phase calcium response |
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