Innervation modulates the functional connectivity between pancreatic endocrine cells
- Max Planck Institute for Heart and Lung Research, Germany
- University of Oxford, United Kingdom
- National Institute of Genetics, Japan
Abstract
The importance of pancreatic endocrine cell activity modulation by autonomic innervation has been debated. To investigate this question, we established an in vivo imaging model that also allows chronic and acute neuromodulation with genetic and optogenetic tools. Using the GCaMP6s biosensor together with endocrine cell fluorescent reporters, we imaged calcium dynamics simultaneously in multiple pancreatic islet cell types in live animals in control states and upon changes in innervation. We find that by 4 days post fertilization in zebrafish, a stage when islet architecture is reminiscent of that in adult rodents, prominent activity coupling between beta cells is present in basal glucose conditions. Furthermore, we show that both chronic and acute loss of nerve activity result in diminished beta-beta and alpha-beta activity coupling. Pancreatic nerves are in contact with all islet cell types, but predominantly with beta and delta cells. Surprisingly, a subset of delta cells with detectable peri-islet neural activity coupling had significantly higher homotypic coupling with other delta cells suggesting that some delta cells receive innervation that coordinates their output. Overall, these data show that innervation plays a vital role in the maintenance of homotypic and heterotypic cellular connectivity in pancreatic islets, a process critical for islet function.
Data availability
All data generated or analysed during this study are included in the manuscript, figures, and figure legends. Source data files have been provided for Figures 1, 2, 3, and 5.
Article and author information
Author details
Yu Hsuan Carol Yang
Sri Teja Mullapudi
Didier YR Stainier
Funding
Max Planck Society
- Didier YR Stainier
Canadian Institutes of Health Research
- Yu Hsuan Carol Yang
Human Frontier Science Program (LT000159/2015)
- Yu Hsuan Carol Yang
EMBO (ALTF 773-2014)
- Yu Hsuan Carol Yang
NIG-JOINT
- Yu Hsuan Carol Yang
AMED
- Koichi Kawakami
Wellcome Trust
- Linford JB Briant
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 zebrafish husbandry was performed under standard conditions in accordance with institutional (MPG) and national ethical and animal welfare guidelines (Proposal numbers: B2/1041, B2/Anz. 1007, B2/1218). All procedures conform to the guidelines from Directive 2010/63/EU of the European Parliament on the protection of animals used for scientific purposes.
Copyright
© 2022, Yang 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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Innervation modulates the functional connectivity between pancreatic endocrine cells
eLife 11:e64526.
https://doi.org/10.7554/eLife.64526
