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Flipping the switch on the hub cell: Islet desynchronization through cell silencing.
Janita P Hogan1, Bradford E Peercy1
1Department of Mathematics & Statistics, University of Maryland Baltimore County, Baltimore, Maryland, United States of America.
Plos One
|April 8, 2021
Summary
Pancreatic beta cells regulate blood glucose. New research suggests "switch cells," not "hub cells," control islet activity and insulin secretion, challenging previous models.
Area of Science:
- Endocrinology
- Computational Biology
- Cellular Physiology
Background:
- Pancreatic beta cells in islets of Langerhans maintain glucose homeostasis through synchronized insulin secretion.
- Gap junctions coordinate beta cell electrical activity and calcium oscillations.
- Recent studies suggested 'hub cells' regulate islet function, challenging the 'democratic' secretion model.
Purpose of the Study:
- To test the 'hub cell' hypothesis using a mechanistic model of beta cell electrical and calcium dynamics.
- To investigate the role of specific cells in coordinating islet-wide insulin secretion.
Main Methods:
- A computational model simulating beta cell electrical and calcium dynamics in a gap junction-coupled network was developed.
- Functional connectivity networks were derived from simulated calcium traces.
- Network centrality measures were used to identify potential 'hub cells', and their silencing was simulated.
- A systematic cell-silencing approach was employed to identify cells critical for overall islet activity.
Main Results:
- Simulated networks exhibited scale-free functional connectivity, consistent with experimental findings.
- Identified 'hub cells' did not disrupt islet synchronization when silenced.
- A novel cell type, termed 'switch cells', was identified; their silencing effectively halted islet activity, despite not being highly functionally connected.
Conclusions:
- The 'hub cell' hypothesis for islet coordination is not supported by this model.
- Beta cell networks possess 'switch cells' that are critical for regulating overall islet activity and insulin secretion.
- These findings necessitate a re-evaluation of the mechanisms governing pancreatic islet function and glucose homeostasis.
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