Beta-cell intrinsic dynamics rather than gap junction structure dictates subpopulations in the islet functional network
- University of Colorado Anschutz Medical Campus, United States
- University of Birmingham, United Kingdom
Abstract
Diabetes is caused by the inability of electrically coupled, functionally heterogeneous -cells within the pancreatic islet to provide adequate insulin secretion. Functional networks have been used to represent synchronized oscillatory [Ca2+] dynamics and to study -cell subpopulations, which play an important role in driving islet function. The mechanism by which highly synchronized -cell subpopulations drive islet function is unclear. We used experimental and computational techniques to investigate the relationship between functional networks, structural (gap-junction) networks, and intrinsic -cell dynamics in slow and fast oscillating islets. Highly synchronized subpopulations in the functional network were differentiated by intrinsic dynamics, including metabolic activity and KATP channel conductance, more than structural coupling. Consistent with this, intrinsic dynamics were more predictive of high synchronization in the islet functional network as compared to high levels of structural coupling. Finally, dysfunction of gap junctions, which can occur in diabetes, caused decreases in the efficiency and clustering of the functional network. These results indicate that intrinsic dynamics rather than structure drive connections in the functional network and highly synchronized subpopulations, but gap junctions are still essential for overall network efficiency. These findings deepen our interpretation of functional networks and the formation of functional sub-populations in dynamic tissues such as the islet.
Data availability
Raw microscopy imaging data is available on the EMBL-EBI-supported BioImage Archive. Analysis code, Model code, and Simulated Data is available via GitHub at https://github.com/jenniferkbriggs/Functional_and_Structural_Networks.git
Article and author information
Author details
Richard KP Benninger
Funding
National Institutes of Health (R01 DK102950)
- Richard KP Benninger
National Institutes of Health (R01 DK106412)
- Richard KP Benninger
National Science Foundation (Graduate Research Fellowship DGE-1938058_Briggs)
- Jennifer K Briggs
Juvenile Diabetes Research Foundation United States of America (3-PDF-2019-741-A-N)
- Vira Kravets
Beckman Research Institute, City of Hope (UC24 DK104162)
- Vira Kravets
Burroughs Wellcome Fund (25B1756)
- Vira Kravets
National Institutes of Health (DK126360)
- JaeAnn M Dwulet
National Institutes of Health (LM012734)
- David J Albers
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: All animal procedures were performed in accordance with guidelines established by the Institutional Animal Care and Use Committee of the University of Colorado Anschutz Medical campus (protocol 000024). All surgeries were performed under ketamine/xylazine anesthesia, with minimal discomfort to the animals.
Reviewing Editor
- Leslie S Satin, University of Michigan, United States
Version history
- Received: August 31, 2022
- Accepted: November 27, 2023
- Accepted Manuscript published: November 29, 2023 (version 1)
Copyright
© 2023, Briggs et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Beta-cell intrinsic dynamics rather than gap junction structure dictates subpopulations in the islet functional network
eLife 12:e83147.
https://doi.org/10.7554/eLife.83147
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