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...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:PloS one 2021-04, Vol.16 (4), p.e0248974
Hauptverfasser: Hogan, Janita P, Peercy, Bradford E
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
Beschreibung
Zusammenfassung: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.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0248974