| First Author | Makhmutova M | Year | 2021 |
| Journal | Gastroenterology | Volume | 160 |
| Issue | 3 | Pages | 875-888.e11 |
| PubMed ID | 33121946 | Mgi Jnum | J:361294 |
| Mgi Id | MGI:6821768 | Doi | 10.1053/j.gastro.2020.10.034 |
| Citation | Makhmutova M, et al. (2021) Pancreatic beta-Cells Communicate With Vagal Sensory Neurons. Gastroenterology 160(3):875-888.e11 |
| abstractText | 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 beta-cells with vagal sensory neurons, we recorded Ca(2+) responses in individual nodose neurons in vivo while selectively stimulating beta-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 beta-cells and to pancreas infusion with serotonin, but were not sensitive to insulin. Responses to chemogenetic and pharmacologic stimulation of beta-cells were blocked by a 5-HT3R antagonist and were enhanced by increasing serotonin levels in beta-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 beta-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 beta-cells via vagal afferent nerves. |
