1. Enteroendocrine L Cells Sense LPS after Gut Barrier Injury to Enhance GLP-1 Secretion
- Author
-
Lebrun, Lorène J, Lenaerts, Kaatje, Kiers, Dorien, Pais de Barros, Jean-Paul, Le Guern, Naïg, 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, Lagrost, Laurent, Grober, Jacques, Surgery, RS: NUTRIM - R2 - Liver and digestive health, RS: NUTRIM - R2 - Gut-liver homeostasis, MUMC+: MA Heelkunde (9), RS: GROW - R3 - Innovative Cancer Diagnostics & Therapy, Promovendi NTM, MUMC+: DA Pat AIOS (9), Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Department of Surgery [Maastricht, the Netherlands], NUTRIM School of Nutrition and Translational Research in Metabolism [Maastricht, The Netherlands]-Maastricht University Medical Centre (MUMC), Maastricht University [Maastricht]-Maastricht University [Maastricht], Department of Intensive Care Medicine [Nijmegen, the Netherlands], Radboud Institute for Molecular Life Sciences [Nijmegen, the Netherlands]-Radboud Institute for Health Sciences [Nijmegen, the Netherlands]-Radboud Center for Infectious Diseases [Nijmegen, the Netherlands]-Radboud University Medical Center [Nijmegen], Equipe NuTox (LNC - U1231) (NUTOX), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Department of Medicine [Toronto, Canada], Mt. Sinai Hospital [Toronto, Canada]-Lunenfeld-Tanenbaum Research Institute [Toronto, Canada]-University of Toronto [Canada], This work was supported by the INSERM, Centre de Recherches UMR 1231, the University Bourgogne Franche-Comte´ , a French government grant managed by the French National Research Agency under the program ‘‘Investissements d’Avenir’’ with reference ANR-11 LABX-0021, the FEDER, and the Regional Council of Bourgogne Franche-Comte´ . D.J.D. is supported by the Canada Research Chairs program, CIHR grant 154321, and the Banting & Best Diabetes Centre-Novo Nordisk Chair in Incretin Biology., ANR-11-LABX-0021,Lipstic,Lipoprotéines et santé : prévention et traitement des maladies inflammatoires non vasculaires et du(2011), Mandard, Stéphane, Laboratoires d'excellence - Lipoprotéines et santé : prévention et traitement des maladies inflammatoires non vasculaires et du cancer - - Lipstic2011 - ANR-11-LABX-0021 - LABX - VALID, Maastricht University Medical Centre (MUMC), Maastricht University [Maastricht]-Maastricht University [Maastricht]-NUTRIM School of Nutrition and Translational Research in Metabolism [Maastricht, The Netherlands], Radboud University Medical Center [Nijmegen]-Radboud Institute for Health Sciences [Nijmegen, the Netherlands]-Radboud Center for Infectious Diseases [Nijmegen, the Netherlands]-Radboud Institute for Molecular Life Sciences [Nijmegen, the Netherlands], Mt. Sinai Hospital [Toronto, Canada]-University of Toronto [Canada]-Lunenfeld-Tanenbaum Research Institute [Toronto, Canada], ANR-11-LABX-0021,Lipstic,Lipoprotéines et santé : prévention et traitement des maladies inflammatoires non vasculaires et du cancer(2011), Lipides - Nutrition - Cancer [Dijon - U1231] ( LNC ), Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale ( INSERM ), NUTRIM School of Nutrition and Translational Research in Metabolism [Maastricht, The Netherlands]-Maastricht University Medical Center [the Netherlands], Equipe NuTox (LNC - U1231) ( NUTOX ), Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Lunenfeld-Tanenbaum Research Institute [Toronto, ON, Canada]-Mt. Sinai Hospital [Toronto, Canada]-University of Toronto [Canada], ANR-11-LABX-0021/11-LABX-0021,Lipstic,Lipoprotéines et santé : prévention et traitement des maladies inflammatoires non vasculaires et du ( 2011 ), Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale (INSERM), and Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale (INSERM)
- Subjects
Adult ,Male ,endocrine system ,Adolescent ,[ SDV.AEN ] Life Sciences [q-bio]/Food and Nutrition ,lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4] ,LIPOPOLYSACCHARIDE ,Proglucagon ,INSULIN-SECRETION ,DISEASE ,Young Adult ,gut injury ,INFLAMMATION ,Ileum ,Animals ,Humans ,Calcium Signaling ,TLR4 ,PERMEABILITY ,PHYSIOLOGY ,lcsh:QH301-705.5 ,Cells, Cultured ,Aged ,Aged, 80 and over ,GLUCAGON-LIKE PEPTIDE-1 ,enteroendocrine cells ,Interleukin-6 ,Dextran Sulfate ,digestive, oral, and skin physiology ,Middle Aged ,Colitis ,lipopolysaccharides ,RECEPTOR AGONISTS ,glucagon-like peptide 1 ,Mice, Inbred C57BL ,Toll-Like Receptor 4 ,MODEL ,[SDV.AEN] Life Sciences [q-bio]/Food and Nutrition ,MICE ,Proprotein Convertase 1 ,lcsh:Biology (General) ,intestinal ischemia ,Reperfusion Injury ,Cytokines ,Myristic Acids ,[SDV.AEN]Life Sciences [q-bio]/Food and Nutrition ,hormones, hormone substitutes, and hormone antagonists - Abstract
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
- Published
- 2017