Glucokinase activity controls subpopulations of β-cells that alternately lead islet Ca2+ oscillations DOI Open Access

Erli Jin,

Jennifer K. Briggs, Richard K.P. Benninger

et al.

Published: Nov. 7, 2024

Oscillations in insulin secretion, driven by islet Ca 2+ waves, are crucial for glycemic control. Prior studies, performed with single-plane imaging, suggest that subpopulations of electrically coupled β-cells have privileged roles leading and coordinating the propagation waves. Here, we used 3D light-sheet imaging to analyze location activity single within entire at >2 Hz. In contrast network analysis indicates most highly synchronized located center, remain regionally but not cellularly stable between oscillations. This subpopulation, which includes ‘hub cells’, is insensitive changes fuel metabolism induced glucokinase pyruvate kinase activation. initiate wave (‘leaders’) periphery, strikingly, change their identity over time via rotations axis. Glucokinase activation, increased oscillation period, reinforced leader cells stabilized Pyruvate despite increasing frequency, had no effect on cells, indicating origin patterned input. These findings emphasize stochastic nature β-cell control oscillations identify a role spatially patterning ‘leader’ β-cells.

Language: Английский

Exploring pancreatic beta-cell subgroups and their connectivity DOI Creative Commons
Guy A. Rutter, Anne Gresch, Luis Fernando Delgadillo-Silva

et al.

Nature Metabolism, Journal Year: 2024, Volume and Issue: 6(11), P. 2039 - 2053

Published: Aug. 8, 2024

Language: Английский

Citations

10

Functional characteristics of hub and wave-initiator cells in β cell networks DOI Creative Commons

Marko Šterk,

Jurij Dolenšek, Maša Skelin Klemen

et al.

Biophysical Journal, Journal Year: 2023, Volume and Issue: 122(5), P. 784 - 801

Published: Feb. 2, 2023

Islets of Langerhans operate as multicellular networks in which several hundred β cells work synchrony to produce secretory pulses insulin, a hormone crucial for controlling metabolic homeostasis. Their collective rhythmic activity is facilitated by gap junctional coupling and affected their functional heterogeneity, but the details this robust coordinated behavior are still not fully understood. Recent advances imaging optogenetic photopharmacological strategies, well network science, have led discovery specialized cell subpopulations that were suggested critically determine dynamics islets. In particular hubs, i.e., with many connections, believed significantly enhance communication capacities intercellular facilitate an efficient spreading Ca

Language: Английский

Citations

16

Network representation of multicellular activity in pancreatic islets: Technical considerations for functional connectivity analysis DOI Creative Commons

Marko Šterk,

Yaowen Zhang, Viljem Pohorec

et al.

PLoS Computational Biology, Journal Year: 2024, Volume and Issue: 20(5), P. e1012130 - e1012130

Published: May 13, 2024

Within the islets of Langerhans, beta cells orchestrate synchronized insulin secretion, a pivotal aspect metabolic homeostasis. Despite inherent heterogeneity and multimodal activity individual cells, intercellular coupling acts as homogenizing force, enabling coordinated responses through propagation waves. Disruptions in this coordination are implicated irregular hallmark diabetes. Recently, innovative approaches, such integrating multicellular calcium imaging with network analysis, have emerged for quantitative assessment cellular islets. However, different groups use distinct experimental preparations, microscopic techniques, apply methods to process measured signals various derive functional connectivity patterns. This makes comparisons between findings their integration into bigger picture difficult has led disputes interpretations. To address these issues, we present here systematic analysis how approaches influence representation islet activity. Our show that choice used construct networks is not crucial, although care needed when combining data from Conversely, conclusions drawn can be heavily affected by pre-processing time series, type oscillatory component signals, preparation. tutorial-like investigation aims resolve interpretational reconcile conflicting views, advance implications, encourage researchers adopt analysis. As conclude, outline challenges future research, emphasizing broader applicability our other tissues exhibiting complex dynamics.

Language: Английский

Citations

5

CRISP: Correlation-Refined Image Segmentation Process DOI Creative Commons
Jennifer K. Briggs,

Erli Jin,

Matthew J. Merrins

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 26, 2024

Calcium imaging enables real-time recording of cellular activity across various biological contexts. To assess the individual cells, scientists typically manually outline cells based on visual inspection. This manual cell masking introduces potential user error. ameliorate this error, we developed Correlation-Refined Image Segmentation Process (CRISP), a two-part automated algorithm designed to both enhance accuracy user-drawn masks and automatically identify masks. We tested CRISP calcium images densely packed β-cells within islet Langerhans. Because these are islet, traditional clustering-based image segmentation methods struggle outlines. Using isolated from two different mouse phenotypes imaged confocal microscopes, show that is generalizable accurate. test benefit using in functional analyses, improves network analysis utilize characterize distribution β-cell size.

Language: Английский

Citations

5

Beta-cell intrinsic dynamics rather than gap junction structure dictates subpopulations in the islet functional network DOI Creative Commons
Jennifer K. Briggs, Anne Gresch, Isabella Marinelli

et al.

eLife, Journal Year: 2023, Volume and Issue: 12

Published: Nov. 29, 2023

Diabetes is caused by the inability of electrically coupled, functionally heterogeneous β-cells within pancreatic islet to provide adequate insulin secretion. Functional networks have been used represent synchronized oscillatory [Ca2+] dynamics and study β-cell subpopulations, which play an important role in driving function. The mechanism highly subpopulations drive function unclear. We experimental computational techniques investigate relationship between functional networks, structural (gap junction) intrinsic slow fast oscillating islets. Highly network were differentiated dynamics, including metabolic activity KATP channel conductance, more than coupling. Consistent with this, predictive high synchronization as compared levels Finally, dysfunction gap junctions, can occur diabetes, decreases efficiency clustering network. These results indicate that rather structure connections but junctions are still essential for overall efficiency. findings deepen our interpretation formation dynamic tissues such islet.

Language: Английский

Citations

13

Glucokinase activity controls peripherally-located subpopulations of β-cells that lead islet Ca2+ oscillations DOI Open Access

Erli Jin,

Jennifer K. Briggs, Richard K.P. Benninger

et al.

Published: Jan. 9, 2025

Oscillations in insulin secretion, driven by islet Ca 2+ waves, are crucial for glycemic control. Prior studies, performed with single-plane imaging, suggest that subpopulations of electrically coupled β-cells have privileged roles leading and coordinating the propagation waves. Here, we used 3D light- sheet imaging to analyze location activity single within entire at >2 Hz. In contrast network analysis indicates most highly synchronized located center, remain regionally but not cellularly stable between oscillations. This subpopulation, which includes ‘hub cells’, is insensitive changes fuel metabolism induced glucokinase pyruvate kinase activation. initiate wave (‘leaders’) periphery, strikingly, change their identity over time via rotations axis. Glucokinase activation, increased oscillation period, reinforced leader cells stabilized Pyruvate despite increasing frequency, had no effect on cells, indicating origin patterned input. These findings emphasize stochastic nature β-cell control oscillations identify a role spatially patterning ‘leader’ β-cells.

Language: Английский

Citations

0

Glucokinase activity controls peripherally located subpopulations of β-cells that lead islet Ca2+ oscillations DOI Creative Commons

Erli Jin,

Jennifer K. Briggs, Richard K.P. Benninger

et al.

eLife, Journal Year: 2025, Volume and Issue: 13

Published: Feb. 12, 2025

Oscillations in insulin secretion, driven by islet Ca 2+ waves, are crucial for glycemic control. Prior studies, performed with single-plane imaging, suggest that subpopulations of electrically coupled β-cells have privileged roles leading and coordinating the propagation waves. Here, we used three-dimensional (3D) light-sheet imaging to analyze location activity single within entire at >2 Hz. In contrast 3D network analysis indicates most highly synchronized located center, remain regionally but not cellularly stable between oscillations. This subpopulation, which includes ‘hub cells’, is insensitive changes fuel metabolism induced glucokinase pyruvate kinase activation. β-Cells initiate wave (leaders) periphery, strikingly, change their identity over time via rotations axis. Glucokinase activation, increased oscillation period, reinforced leader cells stabilized Pyruvate despite increasing frequency, had no effect on cells, indicating origin patterned input. These findings emphasize stochastic nature β-cell control oscillations identify a role spatially patterning ‘leader’ β-cells.

Language: Английский

Citations

0

Causal interaction of metabolic oscillations in monolayers of Hela cervical cancer cells: emergence of complex networks DOI Creative Commons
Takashi Amemiya, Susumu Shuto,

Izumi Fujita

et al.

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: March 3, 2025

A novel global cooperative phenomenon was observed in monolayers of HeLa cervical cancer cells that exhibited glycolytic oscillations but did not exhibit synchronisation or partial synchronisation. The analysis causality the between cell pairs cell-monolayer sheet revealed a hidden causal interaction network. Furthermore, network exhibits characteristics broad-scale This suggests key perform hub-like function and population forms metabolically connected functional rather than randomly one. Unlike previous work focused on cells, present study analysed oscillating by Convergent Cross Mapping (CCM), which is based phase-space reconstruction time-series data used to find weakly coupled components nonlinear dynamical systems. We believe framework proposed this useful for investigating state group can accelerate studies cellular metabolic phenomena including $$\:\beta\:$$ within islets Langerhans. It would also be applicable systems oscillators may include phenomena.

Language: Английский

Citations

0

Phase synchronisation in coupled oscillator chains with endpoint heterogeneity DOI Creative Commons
Daniel Galvis, Nicolás Verschueren, Kyle C. A. Wedgwood

et al.

Physica D Nonlinear Phenomena, Journal Year: 2025, Volume and Issue: unknown, P. 134610 - 134610

Published: March 1, 2025

Language: Английский

Citations

0

Synchronizing beta cells in the pancreas DOI Creative Commons
Bradford E. Peercy, David J. Hodson

eLife, Journal Year: 2024, Volume and Issue: 13

Published: Jan. 25, 2024

The secretion of insulin from the pancreas relies on both gap junctions and subpopulations beta cells with specific intrinsic properties.

Language: Английский

Citations

3