TY - JOUR
T1 - Pancreatic β-Cells Communicate With Vagal Sensory Neurons
AU - Makhmutova, Madina
AU - Weitz, Jonathan
AU - Tamayo, Alejandro
AU - Pereira, Elizabeth
AU - Boulina, Maria
AU - Almaça, Joana
AU - Rodriguez-Diaz, Rayner
AU - Caicedo, Alejandro
N1 - Funding Information:
Funding This work was supported by the Diabetes Research Institute Foundation and National Institutes of Health National Institute of Diabetes and Digestive and Kidney Diseases grants R56DK084321 (A.C.), R01DK084321 (A.C.), R01DK111538 (A.C.), R01DK113093 (A.C.), and U01DK120456 (A. C.), National Institute of Environmental Health Sciences grants R33ES025673 (A.C.) and R21ES025673 (A.C.), National Institute of Diabetes and Digestive and Kidney Disease grants K01DK111757 (J.A.), R21DK114418 (R.R.-D.), and F31DK112596 (M.M.), the Leona M. and Harry B. Helmsley Charitable Trust grants G-2018PG-T1D034 and G-1912-03552, and the American Heart Association grant 19POST34450054 (J.W.).
Publisher Copyright:
© 2021 AGA Institute
PY - 2021/2
Y1 - 2021/2
N2 - 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.
AB - 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.
KW - Pancreatic Islet
KW - Serotonin
KW - Vagus Nerve
KW - Visceral Sensory Innervation
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U2 - 10.1053/j.gastro.2020.10.034
DO - 10.1053/j.gastro.2020.10.034
M3 - Article
C2 - 33121946
AN - SCOPUS:85100439916
VL - 160
SP - 875-888.e11
JO - Gastroenterology
JF - Gastroenterology
SN - 0016-5085
IS - 3
ER -