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Flipping the switch on the hub cell: Islet desynchronization through cell silencing

Pancreatic β cells, responsible for secreting insulin into the bloodstream and maintaining glucose homeostasis, are organized in the islets of Langerhans as clusters of electrically coupled cells. Gap junctions, connecting neighboring cells, coordinate the behavior of the islet, leading to the synch...

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Autores principales: Hogan, Janita P., Peercy, Bradford E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8031451/
https://www.ncbi.nlm.nih.gov/pubmed/33831017
http://dx.doi.org/10.1371/journal.pone.0248974
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author Hogan, Janita P.
Peercy, Bradford E.
author_facet Hogan, Janita P.
Peercy, Bradford E.
author_sort Hogan, Janita P.
collection PubMed
description Pancreatic β cells, responsible for secreting insulin into the bloodstream and maintaining glucose homeostasis, are organized in the islets of Langerhans as clusters of electrically coupled cells. Gap junctions, connecting neighboring cells, coordinate the behavior of the islet, leading to the synchronized oscillations in the intracellular calcium and insulin secretion in healthy islets. Recent experimental work has shown that silencing special hub cells can lead to a disruption in the coordinated behavior, calling into question the democratic paradigm of islet insulin secretion with more or less equal input from each β cell. Islets were shown to have scale-free functional connectivity and a hub cell whose silencing would lead to a loss of functional connectivity and activity in the islet. A mechanistic model representing the electrical and calcium dynamics of β cells during insulin secretion was applied to a network of cells connected by gap junctions to test the hypothesis of hub cells. Functional connectivity networks were built from the simulated calcium traces, with some networks classified as scale-free, confirming experimental results. Potential hub cells were identified using previously defined centrality measures, but silencing them was unable to desynchronize the islet. Instead, switch cells, which were able to turn off the activity of the islet but were not highly functionally connected, were found via systematically silencing each cell in the network.
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spelling pubmed-80314512021-04-14 Flipping the switch on the hub cell: Islet desynchronization through cell silencing Hogan, Janita P. Peercy, Bradford E. PLoS One Research Article Pancreatic β cells, responsible for secreting insulin into the bloodstream and maintaining glucose homeostasis, are organized in the islets of Langerhans as clusters of electrically coupled cells. Gap junctions, connecting neighboring cells, coordinate the behavior of the islet, leading to the synchronized oscillations in the intracellular calcium and insulin secretion in healthy islets. Recent experimental work has shown that silencing special hub cells can lead to a disruption in the coordinated behavior, calling into question the democratic paradigm of islet insulin secretion with more or less equal input from each β cell. Islets were shown to have scale-free functional connectivity and a hub cell whose silencing would lead to a loss of functional connectivity and activity in the islet. A mechanistic model representing the electrical and calcium dynamics of β cells during insulin secretion was applied to a network of cells connected by gap junctions to test the hypothesis of hub cells. Functional connectivity networks were built from the simulated calcium traces, with some networks classified as scale-free, confirming experimental results. Potential hub cells were identified using previously defined centrality measures, but silencing them was unable to desynchronize the islet. Instead, switch cells, which were able to turn off the activity of the islet but were not highly functionally connected, were found via systematically silencing each cell in the network. Public Library of Science 2021-04-08 /pmc/articles/PMC8031451/ /pubmed/33831017 http://dx.doi.org/10.1371/journal.pone.0248974 Text en © 2021 Hogan, Peercy https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Hogan, Janita P.
Peercy, Bradford E.
Flipping the switch on the hub cell: Islet desynchronization through cell silencing
title Flipping the switch on the hub cell: Islet desynchronization through cell silencing
title_full Flipping the switch on the hub cell: Islet desynchronization through cell silencing
title_fullStr Flipping the switch on the hub cell: Islet desynchronization through cell silencing
title_full_unstemmed Flipping the switch on the hub cell: Islet desynchronization through cell silencing
title_short Flipping the switch on the hub cell: Islet desynchronization through cell silencing
title_sort flipping the switch on the hub cell: islet desynchronization through cell silencing
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8031451/
https://www.ncbi.nlm.nih.gov/pubmed/33831017
http://dx.doi.org/10.1371/journal.pone.0248974
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