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Updated: Sep 28, 2025

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Innervation modulates the functional connectivity between pancreatic endocrine cells.

Yu Hsuan Carol Yang1,2, Linford J B Briant3, Christopher A Raab1

  • 1Department of Developmental Genetics, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany.

Elife
|April 4, 2022
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Summary

Autonomic nerves are crucial for pancreatic islet function, coordinating communication between beta and alpha cells. Loss of nerve activity disrupts this cellular connectivity, impacting islet function.

Keywords:
cell biologydevelopmental biologyheterotypic couplinghomotypic couplingin vivo calcium imaginginnervationoptogeneticspancreatic isletzebrafish

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Area of Science:

  • Endocrinology
  • Neuroscience
  • Cell Biology

Background:

  • The role of autonomic innervation in modulating pancreatic endocrine cell activity remains incompletely understood.
  • Pancreatic islets, responsible for glucose homeostasis, contain diverse endocrine cells whose interactions are vital for function.

Purpose of the Study:

  • To investigate the impact of autonomic innervation on pancreatic islet cellular activity and connectivity.
  • To establish and utilize an in vivo imaging model for real-time monitoring of islet cell dynamics.

Main Methods:

  • Developed a zebrafish in vivo imaging model with genetic and optogenetic tools for chronic and acute neuromodulation.
  • Utilized GCaMP6s biosensor and fluorescent reporters to simultaneously image calcium dynamics in multiple pancreatic islet cell types.
  • Analyzed cellular activity coupling (beta-beta, alpha-beta, delta-delta) under basal and altered innervation conditions.

Main Results:

  • Identified prominent activity coupling between beta cells in basal glucose conditions by 4 days post fertilization in zebrafish.
  • Demonstrated that chronic and acute loss of nerve activity diminishes beta-beta and alpha-beta cell activity coupling.
  • Observed that innervation predominantly contacts beta and delta cells, with a subset of delta cells receiving neural input coordinating their output.

Conclusions:

  • Autonomic innervation is vital for maintaining homotypic and heterotypic cellular connectivity within pancreatic islets.
  • Disruption of innervation impairs intercellular communication, highlighting its critical role in overall islet function.
  • Specific delta cell innervation suggests a role in coordinating delta cell output and potentially influencing islet function.