Enteroendocrine L Cells Sense LPS after Gut Barrier Injury to Enhance GLP-1 Secretion.

Abstract

Glucagon-like peptide 1 (GLP-1) is a hormone released from enteroendocrine L cells. Although first described as a glucoregulatory incretin hormone, GLP-1 also suppresses inflammation and promotes mucosal integrity. Here, we demonstrate that plasma GLP-1 levels are rapidly increased by lipopolysaccharide (LPS) administration in mice via a Toll-like receptor 4 (TLR4)-dependent mechanism. Experimental manipulation of gut barrier integrity after dextran sodium sulfate treatment, or via ischemia/reperfusion experiments in mice, triggered a rapid rise in circulating GLP-1. This phenomenon was detected prior to measurable changes in inflammatory status and plasma cytokine and LPS levels. In human subjects, LPS administration also induced GLP-1 secretion. Furthermore, GLP-1 levels were rapidly increased following the induction of ischemia in the human intestine. These findings expand traditional concepts of enteroendocrine L cell biology to encompass the sensing of inflammatory stimuli and compromised mucosal integrity, linking glucagon-like peptide secretion to gut inflammation.

• Authors: Lorène J Lebrun, Kaatje Lenaerts, Dorien Kiers, Jean-Paul Pais de Barros, Naig Le Guern, Jiri Plesnik, Charles Thomas, Thibaut Bourgeois, Cornelis H C Dejong, Matthijs Kox, Inca H R Hundscheid, Naim Akhtar Khan, Stéphane Mandard, Valérie Deckert, Peter Pickkers, Daniel J Drucker, Laurent Lagrost, Jacques Grober
• Journal: Cell reports (Cell Rep) Vol. 21 Issue 5 Pg. 1160-1168 (Oct 31 2017) ISSN: 2211-1247 [Electronic] United States
• PMID: 29091756 (Publication Type: Journal Article)
• Copyright: Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Chemical References

• Cytokines
• Interleukin-6
• Lipopolysaccharides
• Myristic Acids
• Toll-Like Receptor 4
• beta-hydroxymyristic acid
• Proglucagon
• Glucagon-Like Peptide 1
• Dextran Sulfate
• Pcsk1 protein, mouse
• Proprotein Convertase 1

Topics

• Adolescent
• Adult
• Aged
• Aged, 80 and over
• Animals
• Calcium Signaling (drug effects)
• Cells, Cultured
• Colitis (chemically induced, metabolism, pathology)
• Cytokines (blood, genetics, metabolism)
• Dextran Sulfate (pharmacology)
• Enteroendocrine Cells (cytology, drug effects, metabolism)
• Glucagon-Like Peptide 1 (metabolism)
• Humans
• Ileum (drug effects, metabolism)
• Interleukin-6 (deficiency, genetics)
• Lipopolysaccharides (toxicity)
• Male
• Mice
• Mice, Inbred C57BL
• Middle Aged
• Myristic Acids (blood)
• Proglucagon (metabolism)
• Proprotein Convertase 1 (metabolism)
• Reperfusion Injury (metabolism, pathology)
• Toll-Like Receptor 4 (deficiency, genetics, metabolism)
• Young Adult