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

Publication date: 31 October 2017
Source:Cell Reports, Volume 21, Issue 5
Author(s): 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
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.

Graphical abstract

Teaser

Lebrun et al. demonstrate that enteroendocrine L cells sense lipopolysaccharides (pro-inflammatory bacterial compounds) after gut injury and respond by secreting glucagon-like peptide 1. These findings expand concepts of L cell function to include roles as both a nutrient and pathogen sensor, linking glucagon-like peptide secretion to gut inflammation.


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