
==== Front
bioRxiv
BIORXIV
bioRxiv
2692-8205
Cold Spring Harbor Laboratory

10.1101/2024.08.21.608680
preprint
2
Article
Glucokinase activity controls subpopulations of β-cells that alternately lead islet Ca 2+ oscillations
Jin Erli
Briggs Jennifer K http://orcid.org/0000-0002-8737-2215

Benninger Richard KP
Merrins Matthew J http://orcid.org/0000-0003-1599-9227

22 8 2024
2024.08.21.608680https://creativecommons.org/licenses/by-nc-nd/4.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which allows reusers to copy and distribute the material in any medium or format in unadapted form only, for noncommercial purposes only, and only so long as attribution is given to the creator.
http://biorxiv.org/lookup/doi/10.1101/2024.08.21.608680
nihpp-2024.08.21.608680.pdf
Ca 2+ -driven oscillations in insulin secretion are crucial for glycemic control. Prior studies, performed with single-plane imaging, suggest that subpopulations of electrically coupled β-cells have privileged roles in leading and coordinating the propagation of Ca 2+ waves. Here, we used 3D light-sheet imaging to analyze the location and Ca 2+ activity of single β-cells within the entire islet at >2 Hz. Network analysis indicates that the most highly synchronized β-cells are located at the islet center and remain geographically stable between oscillations. In contrast, β-cells that initiate the Ca 2+ wave ('leaders') are located at the islet periphery and change their identity over time via rotations in the wave axis. Activators of glucokinase and pyruvate kinase were used to further test the influence of glycolysis on these β-cell subpopulations. Glucokinase activation, which increased oscillation period, reinforced leader cells and stabilized the wave axis. Pyruvate kinase activation, despite increasing oscillation frequency, had no effect on leader cells, indicating the wave origin is patterned by fuel input. The 3D islet β-cell network, which did not respond to either treatment, is insensitive to changes in fuel metabolism. These findings emphasize the stochastic nature of Ca 2+ oscillations and identify a role for glucokinase in spatially patterning 'leader' β-cells.
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pmc
