Pancreatic β-Cells Communicate With Vagal Sensory Neurons

Madina Makhmutova, Jonathan Weitz, Alejandro Tamayo, Elizabeth Pereira, Maria Boulina, Joana Almaça, Rayner Rodriguez-Diaz, Alejandro Caicedo

Research output: Contribution to journalArticlepeer-review

12 Scopus citations


Background And Aims: Destroying visceral sensory nerves impacts pancreatic islet function, glucose metabolism, and diabetes onset, but how islet endocrine cells interact with sensory neurons has not been studied. Methods: We characterized the anatomical pattern of pancreatic sensory innervation by combining viral tracing, immunohistochemistry, and reporter mouse models. To assess the functional interactions of β-cells with vagal sensory neurons, we recorded Ca2+ responses in individual nodose neurons in vivo while selectively stimulating β-cells with chemogenetic and pharmacologic approaches. Results: We found that pancreatic islets are innervated by vagal sensory axons expressing Phox2b, substance P, calcitonin-gene related peptide, and the serotonin receptor 5-HT3R. Centrally, vagal neurons projecting to the pancreas terminate in the commissural nucleus of the solitary tract. Nodose neurons responded in vivo to chemogenetic stimulation of β-cells and to pancreas infusion with serotonin, but were not sensitive to insulin. Responses to chemogenetic and pharmacologic stimulation of β-cells were blocked by a 5-HT3R antagonist and were enhanced by increasing serotonin levels in β-cells. We further confirmed directly in living pancreas slices that sensory terminals in the islet were sensitive to serotonin. Conclusions: Our study establishes that pancreatic β-cells communicate with vagal sensory neurons, likely using serotonin signaling as a transduction mechanism. Serotonin is coreleased with insulin and may therefore convey information about the secretory state of β-cells via vagal afferent nerves.

Original languageEnglish (US)
Pages (from-to)875-888.e11
Issue number3
StatePublished - Feb 2021


  • Pancreatic Islet
  • Serotonin
  • Vagus Nerve
  • Visceral Sensory Innervation

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology


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