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, distinc...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2022-09-01
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| Series: | PLoS Biology |
| Online Access: | https://doi.org/10.1371/journal.pbio.3001761 |
| _version_ | 1811238979991764992 |
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| author | Vira Kravets JaeAnn M Dwulet Wolfgang E Schleicher David J Hodson Anna M Davis Laura Pyle Robert A Piscopio Maura Sticco-Ivins Richard K P Benninger |
| author_facet | Vira Kravets JaeAnn M Dwulet Wolfgang E Schleicher David J Hodson Anna M Davis Laura Pyle Robert A Piscopio Maura Sticco-Ivins Richard K P Benninger |
| author_sort | Vira Kravets |
| collection | DOAJ |
| 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 | 2024-04-12T12:51:50Z |
| format | Article |
| id | doaj.art-9640275cc251401eb2cb503ecea4e967 |
| institution | Directory Open Access Journal |
| issn | 1544-9173 1545-7885 |
| language | English |
| last_indexed | 2024-04-12T12:51:50Z |
| publishDate | 2022-09-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Biology |
| spelling | doaj.art-9640275cc251401eb2cb503ecea4e9672022-12-22T03:32:27ZengPublic Library of Science (PLoS)PLoS Biology1544-91731545-78852022-09-01209e300176110.1371/journal.pbio.3001761Functional architecture of pancreatic islets identifies a population of first responder cells that drive the first-phase calcium response.Vira KravetsJaeAnn M DwuletWolfgang E SchleicherDavid J HodsonAnna M DavisLaura PyleRobert A PiscopioMaura Sticco-IvinsRichard K P BenningerInsulin-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.https://doi.org/10.1371/journal.pbio.3001761 |
| spellingShingle | Vira Kravets JaeAnn M Dwulet Wolfgang E Schleicher David J Hodson Anna M Davis Laura Pyle Robert A Piscopio Maura Sticco-Ivins Richard K P Benninger Functional architecture of pancreatic islets identifies a population of first responder cells that drive the first-phase calcium response. PLoS Biology |
| 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 |
| url | https://doi.org/10.1371/journal.pbio.3001761 |
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