Details

Autor(en) / Beteiligte

• Lebrun, Lorène J.
• Lenaerts, Kaatje
• Kiers, Dorien
• Pais de Barros, Jean-Paul
• Le Guern, Naig
• Plesnik, Jiri
• Thomas, Charles
• Bourgeois, Thibaut
• Dejong, Cornelis H.C.
• Kox, Matthijs
• Hundscheid, Inca H.R.
• Khan, Naim Akhtar
• Mandard, Stéphane
• Deckert, Valérie
• Pickkers, Peter
• Drucker, Daniel J.
• Lagrost, Laurent
• Grober, Jacques

Titel

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

Ist Teil von

• Cell reports (Cambridge), 2017-10, Vol.21 (5), p.1160-1168

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2017

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• 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. [Display omitted] •LPS induce GLP-1 secretion from L cells through a TLR4-dependent mechanism•Gut ischemic injury is coupled to immediate GLP-1 secretion in mice and humans•L cells are mucosal sensors of LPS after gut injury•GLP-1 secretion is closely related 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.