Cell Reports (Oct 2017)

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

  • 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 volume & issue
Vol. 21, no. 5
pp. 1160 – 1168

Abstract

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Summary: 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. : 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. Keywords: glucagon-like peptide 1, lipopolysaccharides, enteroendocrine cells, TLR4, gut injury, intestinal ischemia, inflammation