Enteroendocrine L Cells Sense LPS after Gut Barrier Injury to Enhance GLP-1 Secretion.
Fiche publication
Date publication
octobre 2017
Journal
Cell reports
Auteurs
Membres identifiés du Cancéropôle Est :
Dr LAGROST Laurent, Dr PAIS DE BARROS Jean-Paul
Tous les auteurs :
Lebrun LJ, Lenaerts K, Kiers D, Pais de Barros JP, Le Guern N, Plesnik J, Thomas C, Bourgeois T, Dejong CHC, Kox M, Hundscheid IHR, Khan NA, Mandard S, Deckert V, Pickkers P, Drucker DJ, Lagrost L, Grober J
Lien Pubmed
Résumé
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.
Mots clés
TLR4, enteroendocrine cells, glucagon-like peptide 1, gut injury, inflammation, intestinal ischemia, lipopolysaccharides
Référence
Cell Rep. 2017 Oct 31;21(5):1160-1168