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

Lorene 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, Stephane Mandard, Valerie Deckert, Peter Pickkers, Daniel J. Drucker, Laurent Lagrost, Jacques Grober*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

91 Citations (Web of Science)

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.

Original languageEnglish
Pages (from-to)1160-1168
Number of pages9
JournalCell Reports
Volume21
Issue number5
DOIs
Publication statusPublished - 31 Oct 2017

Keywords

  • GLUCAGON-LIKE PEPTIDE-1
  • INSULIN-SECRETION
  • RECEPTOR AGONISTS
  • MICE
  • INFLAMMATION
  • DISEASE
  • LIPOPOLYSACCHARIDE
  • MODEL
  • PERMEABILITY
  • PHYSIOLOGY

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