Dynamin regulates L cell secretion in human gut.
Adult
Aged
Animals
Cells, Cultured
Culture Media
/ chemistry
Cyanoacrylates
/ pharmacology
Dynamin I
/ metabolism
Dynamin II
/ metabolism
Enteroendocrine Cells
/ cytology
Female
Glucagon-Like Peptide 1
/ metabolism
Humans
Indoles
/ pharmacology
Intestinal Mucosa
/ cytology
L Cells
Male
Mice
Middle Aged
Peptide YY
/ metabolism
Tyrphostins
/ pharmacology
Dynamin
Enteroendocrine cells
GLP-1
Gut hormones
PYY
Journal
Molecular and cellular endocrinology
ISSN: 1872-8057
Titre abrégé: Mol Cell Endocrinol
Pays: Ireland
ID NLM: 7500844
Informations de publication
Date de publication:
15 09 2021
15 09 2021
Historique:
received:
24
11
2020
revised:
01
06
2021
accepted:
13
07
2021
pubmed:
19
7
2021
medline:
27
1
2022
entrez:
18
7
2021
Statut:
ppublish
Résumé
The mechanochemical enzyme dynamin mediates endocytosis and regulates neuroendocrine cell exocytosis. Enteroendocrine L cells co-secrete the anorectic gut hormones glucagon-like peptide 1 (GLP-1) and peptide YY (PYY) postprandially and is a potential therapeutic target for metabolic diseases. In the present study, we aimed to determine if dynamin is implicated in human L cell secretion. Western blot was performed on the murine L cell line GLUTag. Static incubation of human colonic mucosae with activators and inhibitors of dynamin was carried out. GLP-1 and PYY contents of the secretion supernatants were assayed using ELISA. s: Both dynamin I and II are expressed in GLUTag cells. The dynamin activator Ryngo 1-23 evoked significant GLP-1 and PYY release from human colonic mucosae while the dynamin inhibitor Dynole 3-42 significantly inhibited release triggered by known L cell secretagogues. Thus, the cell signaling regulator dynamin is able to bi-directionally regulate L cell hormone secretion in the human gut and may represent a novel target for gastrointestinal-targeted metabolic drug development.
Sections du résumé
BACKGROUND
The mechanochemical enzyme dynamin mediates endocytosis and regulates neuroendocrine cell exocytosis. Enteroendocrine L cells co-secrete the anorectic gut hormones glucagon-like peptide 1 (GLP-1) and peptide YY (PYY) postprandially and is a potential therapeutic target for metabolic diseases. In the present study, we aimed to determine if dynamin is implicated in human L cell secretion.
METHODS
Western blot was performed on the murine L cell line GLUTag. Static incubation of human colonic mucosae with activators and inhibitors of dynamin was carried out. GLP-1 and PYY contents of the secretion supernatants were assayed using ELISA.
RESULTS AND CONCLUSION
s: Both dynamin I and II are expressed in GLUTag cells. The dynamin activator Ryngo 1-23 evoked significant GLP-1 and PYY release from human colonic mucosae while the dynamin inhibitor Dynole 3-42 significantly inhibited release triggered by known L cell secretagogues. Thus, the cell signaling regulator dynamin is able to bi-directionally regulate L cell hormone secretion in the human gut and may represent a novel target for gastrointestinal-targeted metabolic drug development.
Identifiants
pubmed: 34274446
pii: S0303-7207(21)00242-2
doi: 10.1016/j.mce.2021.111398
pii:
doi:
Substances chimiques
Culture Media
0
Cyanoacrylates
0
Indoles
0
Ryngo 1-23
0
Tyrphostins
0
dynole 34-2
0
Peptide YY
106388-42-5
Glucagon-Like Peptide 1
89750-14-1
Dynamin I
EC 3.5.1.50
DNM2 protein, human
EC 3.6.5.5
Dynamin II
EC 3.6.5.5
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
111398Informations de copyright
Copyright © 2021. Published by Elsevier B.V.