Colonic Motility Is Improved by the Activation of 5-HT
Animals
Calcium Signaling
Colon
/ drug effects
Constipation
/ etiology
Diabetes Complications
/ metabolism
Disease Models, Animal
Female
Gastrointestinal Motility
/ drug effects
Genes, Reporter
Indoles
/ pharmacology
Interstitial Cells of Cajal
/ drug effects
Male
Mice, Inbred C57BL
Mice, Transgenic
Myoelectric Complex, Migrating
/ drug effects
Ovariectomy
Proto-Oncogene Proteins c-kit
/ genetics
Receptor, Serotonin, 5-HT2B
/ drug effects
Serotonin
/ metabolism
Serotonin 5-HT2 Receptor Agonists
/ pharmacology
Thiophenes
/ pharmacology
Tryptophan Hydroxylase
/ genetics
5-HT(2B)
Constipation
Diabetes
ICCs
Serotonin
Journal
Gastroenterology
ISSN: 1528-0012
Titre abrégé: Gastroenterology
Pays: United States
ID NLM: 0374630
Informations de publication
Date de publication:
08 2021
08 2021
Historique:
received:
30
09
2020
revised:
15
04
2021
accepted:
17
04
2021
pubmed:
26
4
2021
medline:
19
1
2022
entrez:
25
4
2021
Statut:
ppublish
Résumé
Constipation is commonly associated with diabetes. Serotonin (5-HT), produced predominantly by enterochromaffin (EC) cells via tryptophan hydroxylase 1 (TPH1), is a key modulator of gastrointestinal (GI) motility. However, the role of serotonergic signaling in constipation associated with diabetes is unknown. We generated EC cell reporter Tph1-tdTom, EC cell-depleted Tph1-DTA, combined Tph1-tdTom-DTA, and interstitial cell of Cajal (ICC)-specific Kit-GCaMP6 mice. Male mice and surgically ovariectomized female mice were fed a high-fat high-sucrose diet to induce diabetes. The effect of serotonergic signaling on GI motility was studied by examining 5-HT receptor expression in the colon and in vivo GI transit, colonic migrating motor complexes (CMMCs), and calcium imaging in mice treated with either a 5-HT Colonic transit was delayed in males with diabetes, although colonic Tph1 Impaired colonic motility in mice with diabetes was improved by enhancing HTR2B signaling. The HTR2B agonist may provide therapeutic benefits for constipation associated with diabetes.
Sections du résumé
BACKGROUND & AIMS
Constipation is commonly associated with diabetes. Serotonin (5-HT), produced predominantly by enterochromaffin (EC) cells via tryptophan hydroxylase 1 (TPH1), is a key modulator of gastrointestinal (GI) motility. However, the role of serotonergic signaling in constipation associated with diabetes is unknown.
METHODS
We generated EC cell reporter Tph1-tdTom, EC cell-depleted Tph1-DTA, combined Tph1-tdTom-DTA, and interstitial cell of Cajal (ICC)-specific Kit-GCaMP6 mice. Male mice and surgically ovariectomized female mice were fed a high-fat high-sucrose diet to induce diabetes. The effect of serotonergic signaling on GI motility was studied by examining 5-HT receptor expression in the colon and in vivo GI transit, colonic migrating motor complexes (CMMCs), and calcium imaging in mice treated with either a 5-HT
RESULTS
Colonic transit was delayed in males with diabetes, although colonic Tph1
CONCLUSIONS
Impaired colonic motility in mice with diabetes was improved by enhancing HTR2B signaling. The HTR2B agonist may provide therapeutic benefits for constipation associated with diabetes.
Identifiants
pubmed: 33895170
pii: S0016-5085(21)00678-8
doi: 10.1053/j.gastro.2021.04.040
pmc: PMC8532042
mid: NIHMS1696788
pii:
doi:
Substances chimiques
1-(5-(2-thenyloxy)-1H-indol-3-yl)propan-2-amine
0
Indoles
0
Kit protein, mouse
0
Receptor, Serotonin, 5-HT2B
0
Serotonin 5-HT2 Receptor Agonists
0
Thiophenes
0
Serotonin
333DO1RDJY
Tph1 protein, mouse
EC 1.14.16.4
Tryptophan Hydroxylase
EC 1.14.16.4
Proto-Oncogene Proteins c-kit
EC 2.7.10.1
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Video-Audio Media
Langues
eng
Sous-ensembles de citation
IM
Pagination
608-622.e7Subventions
Organisme : NIDDK NIH HHS
ID : R21 DK091725
Pays : United States
Organisme : NIGMS NIH HHS
ID : P30 GM110767
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK120759
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK103055
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK094886
Pays : United States
Organisme : NIDDK NIH HHS
ID : P01 DK041315
Pays : United States
Commentaires et corrections
Type : ErratumIn
Informations de copyright
Copyright © 2021 AGA Institute. Published by Elsevier Inc. All rights reserved.
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