Innervation modulates the functional connectivity between pancreatic endocrine cells

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.