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Suppression of Glucagon-Like Peptide-1 Release by Inhibition of Intestinal NLRP3 Inflammasome Activation in Asc(–/–) and Nlrp3(–/–) Mice
The glucagon-like peptide-1 (GLP-1) is an insulinotropic hormone secreted by intestinal enteroendocrine L-cells, which plays a crucial role in glucose control, regulation, and protection from different pathological conditions such as diabetes mellitus. The present study sought to test whether GLP-1...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6779826/ https://www.ncbi.nlm.nih.gov/pubmed/31632284 http://dx.doi.org/10.3389/fphys.2019.01213 |
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author | Chen, Yu Kidd, Jason Bhat, Owais M. Yuan, Xinxu Hong, Jinni He, Xingxiang Li, Pin-Lan |
author_facet | Chen, Yu Kidd, Jason Bhat, Owais M. Yuan, Xinxu Hong, Jinni He, Xingxiang Li, Pin-Lan |
author_sort | Chen, Yu |
collection | PubMed |
description | The glucagon-like peptide-1 (GLP-1) is an insulinotropic hormone secreted by intestinal enteroendocrine L-cells, which plays a crucial role in glucose control, regulation, and protection from different pathological conditions such as diabetes mellitus. The present study sought to test whether GLP-1 release increases gut injury with a high-fat diet (HFD) and whether this GLP-1 release is associated with NLRP3 inflammasome activation. Our results showed that the NLRP3 inflammasome is activated in the intestinal tissue of wild-type mice on a HFD, accompanied by GLP-1 overexpression. The number of intestinal L-cells and the GLP-1 level in serum are increased in WT mice with HFD. However, in the Asc(–/–) and Nlrp3(–/–) mice, these HFD-induced intestinal and serum GLP-1 changes were suppressed. Using confocal microscopy, the colocalization of GLP-1 and FLICA that labels activated caspase-1 in intestine was decreased in the Asc(–/–) and Nlrp3(–/–) mice compared to WT mice. Mechanistically, the inhibitor of caspase-1 or HMGB1 blocker is used to demonstrate the regulatory action of NRLP3 inflammasome in GLP-1 release. It was found that the level of GLP-1 and its colocalization with IL-1β were reduced by inhibition of the caspase-1 activity, but not altered by blockade of HMGB1 action. Our results suggest that NLRP3 inflammasome activation triggers GLP-1 production from the intestine, which is associated with IL-1β, but not with HMGB1. These findings for the first time provide evidence that the activation of NLRP3 inflammasome in the intestine increases GLP-1 release in mice, which may serve as an adaptive response to intestinal inflammation. |
format | Online Article Text |
id | pubmed-6779826 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-67798262019-10-18 Suppression of Glucagon-Like Peptide-1 Release by Inhibition of Intestinal NLRP3 Inflammasome Activation in Asc(–/–) and Nlrp3(–/–) Mice Chen, Yu Kidd, Jason Bhat, Owais M. Yuan, Xinxu Hong, Jinni He, Xingxiang Li, Pin-Lan Front Physiol Physiology The glucagon-like peptide-1 (GLP-1) is an insulinotropic hormone secreted by intestinal enteroendocrine L-cells, which plays a crucial role in glucose control, regulation, and protection from different pathological conditions such as diabetes mellitus. The present study sought to test whether GLP-1 release increases gut injury with a high-fat diet (HFD) and whether this GLP-1 release is associated with NLRP3 inflammasome activation. Our results showed that the NLRP3 inflammasome is activated in the intestinal tissue of wild-type mice on a HFD, accompanied by GLP-1 overexpression. The number of intestinal L-cells and the GLP-1 level in serum are increased in WT mice with HFD. However, in the Asc(–/–) and Nlrp3(–/–) mice, these HFD-induced intestinal and serum GLP-1 changes were suppressed. Using confocal microscopy, the colocalization of GLP-1 and FLICA that labels activated caspase-1 in intestine was decreased in the Asc(–/–) and Nlrp3(–/–) mice compared to WT mice. Mechanistically, the inhibitor of caspase-1 or HMGB1 blocker is used to demonstrate the regulatory action of NRLP3 inflammasome in GLP-1 release. It was found that the level of GLP-1 and its colocalization with IL-1β were reduced by inhibition of the caspase-1 activity, but not altered by blockade of HMGB1 action. Our results suggest that NLRP3 inflammasome activation triggers GLP-1 production from the intestine, which is associated with IL-1β, but not with HMGB1. These findings for the first time provide evidence that the activation of NLRP3 inflammasome in the intestine increases GLP-1 release in mice, which may serve as an adaptive response to intestinal inflammation. Frontiers Media S.A. 2019-10-01 /pmc/articles/PMC6779826/ /pubmed/31632284 http://dx.doi.org/10.3389/fphys.2019.01213 Text en Copyright © 2019 Chen, Kidd, Bhat, Yuan, Hong, He and Li. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Physiology Chen, Yu Kidd, Jason Bhat, Owais M. Yuan, Xinxu Hong, Jinni He, Xingxiang Li, Pin-Lan Suppression of Glucagon-Like Peptide-1 Release by Inhibition of Intestinal NLRP3 Inflammasome Activation in Asc(–/–) and Nlrp3(–/–) Mice |
title | Suppression of Glucagon-Like Peptide-1 Release by Inhibition of Intestinal NLRP3 Inflammasome Activation in Asc(–/–) and Nlrp3(–/–) Mice |
title_full | Suppression of Glucagon-Like Peptide-1 Release by Inhibition of Intestinal NLRP3 Inflammasome Activation in Asc(–/–) and Nlrp3(–/–) Mice |
title_fullStr | Suppression of Glucagon-Like Peptide-1 Release by Inhibition of Intestinal NLRP3 Inflammasome Activation in Asc(–/–) and Nlrp3(–/–) Mice |
title_full_unstemmed | Suppression of Glucagon-Like Peptide-1 Release by Inhibition of Intestinal NLRP3 Inflammasome Activation in Asc(–/–) and Nlrp3(–/–) Mice |
title_short | Suppression of Glucagon-Like Peptide-1 Release by Inhibition of Intestinal NLRP3 Inflammasome Activation in Asc(–/–) and Nlrp3(–/–) Mice |
title_sort | suppression of glucagon-like peptide-1 release by inhibition of intestinal nlrp3 inflammasome activation in asc(–/–) and nlrp3(–/–) mice |
topic | Physiology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6779826/ https://www.ncbi.nlm.nih.gov/pubmed/31632284 http://dx.doi.org/10.3389/fphys.2019.01213 |
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