Enteroendocrine L Cells Sense LPS after Gut Barrier Injury to Enhance GLP-1 Secretion
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 lipop...
| Main Authors: | , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2017-10-01
|
| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124717314250 |
| _version_ | 1830430900126482432 |
|---|---|
| author | 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 |
| author_facet | 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 |
| author_sort | Lorène J. Lebrun |
| collection | DOAJ |
| description | 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 |
| first_indexed | 2024-12-21T01:58:01Z |
| format | Article |
| id | doaj.art-54c442ddf2554e8d93b3af382d5f41cd |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-21T01:58:01Z |
| publishDate | 2017-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-54c442ddf2554e8d93b3af382d5f41cd2022-12-21T19:19:42ZengElsevierCell Reports2211-12472017-10-0121511601168Enteroendocrine L Cells Sense LPS after Gut Barrier Injury to Enhance GLP-1 SecretionLorène J. Lebrun0Kaatje Lenaerts1Dorien Kiers2Jean-Paul Pais de Barros3Naig Le Guern4Jiri Plesnik5Charles Thomas6Thibaut Bourgeois7Cornelis H.C. Dejong8Matthijs Kox9Inca H.R. Hundscheid10Naim Akhtar Khan11Stéphane Mandard12Valérie Deckert13Peter Pickkers14Daniel J. Drucker15Laurent Lagrost16Jacques Grober17INSERM LNC UMR 1231, 21000 Dijon, France; University Bourgogne Franche-Comté, LNC UMR 1231, 21000 Dijon, France; LipSTIC LabEx, Fondation de Coopération Scientifique Bourgogne Franche-Comté, 21000 Dijon, FranceDepartment of Surgery, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center, 62000 MD Maastricht, the NetherlandsDepartment of Intensive Care Medicine, Radboud Institute for Health Sciences, Radboud Center for Infectious Diseases, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, 65000 HB Nijmegen, the NetherlandsINSERM LNC UMR 1231, 21000 Dijon, France; University Bourgogne Franche-Comté, LNC UMR 1231, 21000 Dijon, France; LipSTIC LabEx, Fondation de Coopération Scientifique Bourgogne Franche-Comté, 21000 Dijon, FranceINSERM LNC UMR 1231, 21000 Dijon, France; University Bourgogne Franche-Comté, LNC UMR 1231, 21000 Dijon, France; LipSTIC LabEx, Fondation de Coopération Scientifique Bourgogne Franche-Comté, 21000 Dijon, FranceINSERM LNC UMR 1231, 21000 Dijon, France; University Bourgogne Franche-Comté, LNC UMR 1231, 21000 Dijon, France; LipSTIC LabEx, Fondation de Coopération Scientifique Bourgogne Franche-Comté, 21000 Dijon, FranceINSERM LNC UMR 1231, 21000 Dijon, France; University Bourgogne Franche-Comté, LNC UMR 1231, 21000 Dijon, France; LipSTIC LabEx, Fondation de Coopération Scientifique Bourgogne Franche-Comté, 21000 Dijon, FranceINSERM LNC UMR 1231, 21000 Dijon, France; University Bourgogne Franche-Comté, LNC UMR 1231, 21000 Dijon, France; LipSTIC LabEx, Fondation de Coopération Scientifique Bourgogne Franche-Comté, 21000 Dijon, FranceDepartment of Surgery, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center, 62000 MD Maastricht, the Netherlands; Department of Surgery, Universitätsklinikum Aachen, 52074 Aachen, GermanyDepartment of Intensive Care Medicine, Radboud Institute for Health Sciences, Radboud Center for Infectious Diseases, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, 65000 HB Nijmegen, the NetherlandsDepartment of Surgery, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center, 62000 MD Maastricht, the NetherlandsINSERM LNC UMR 1231, 21000 Dijon, France; University Bourgogne Franche-Comté, LNC UMR 1231, 21000 Dijon, France; LipSTIC LabEx, Fondation de Coopération Scientifique Bourgogne Franche-Comté, 21000 Dijon, FranceINSERM LNC UMR 1231, 21000 Dijon, France; University Bourgogne Franche-Comté, LNC UMR 1231, 21000 Dijon, France; LipSTIC LabEx, Fondation de Coopération Scientifique Bourgogne Franche-Comté, 21000 Dijon, FranceINSERM LNC UMR 1231, 21000 Dijon, France; University Bourgogne Franche-Comté, LNC UMR 1231, 21000 Dijon, France; LipSTIC LabEx, Fondation de Coopération Scientifique Bourgogne Franche-Comté, 21000 Dijon, FranceDepartment of Intensive Care Medicine, Radboud Institute for Health Sciences, Radboud Center for Infectious Diseases, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, 65000 HB Nijmegen, the NetherlandsDepartment of Medicine, Lunenfeld-Tanenbaum Research Institute, Mt. Sinai Hospital, University of Toronto, Toronto, ON M5G 1X5, CanadaINSERM LNC UMR 1231, 21000 Dijon, France; University Bourgogne Franche-Comté, LNC UMR 1231, 21000 Dijon, France; LipSTIC LabEx, Fondation de Coopération Scientifique Bourgogne Franche-Comté, 21000 Dijon, France; University Hospital of Dijon, 21000 Dijon, FranceINSERM LNC UMR 1231, 21000 Dijon, France; University Bourgogne Franche-Comté, LNC UMR 1231, 21000 Dijon, France; LipSTIC LabEx, Fondation de Coopération Scientifique Bourgogne Franche-Comté, 21000 Dijon, France; AgroSup Dijon, 21000 Dijon, France; Corresponding authorSummary: 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, inflammationhttp://www.sciencedirect.com/science/article/pii/S2211124717314250 |
| spellingShingle | 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 Enteroendocrine L Cells Sense LPS after Gut Barrier Injury to Enhance GLP-1 Secretion Cell Reports |
| title | Enteroendocrine L Cells Sense LPS after Gut Barrier Injury to Enhance GLP-1 Secretion |
| title_full | Enteroendocrine L Cells Sense LPS after Gut Barrier Injury to Enhance GLP-1 Secretion |
| title_fullStr | Enteroendocrine L Cells Sense LPS after Gut Barrier Injury to Enhance GLP-1 Secretion |
| title_full_unstemmed | Enteroendocrine L Cells Sense LPS after Gut Barrier Injury to Enhance GLP-1 Secretion |
| title_short | Enteroendocrine L Cells Sense LPS after Gut Barrier Injury to Enhance GLP-1 Secretion |
| title_sort | enteroendocrine l cells sense lps after gut barrier injury to enhance glp 1 secretion |
| url | http://www.sciencedirect.com/science/article/pii/S2211124717314250 |
| work_keys_str_mv | AT lorenejlebrun enteroendocrinelcellssenselpsaftergutbarrierinjurytoenhanceglp1secretion AT kaatjelenaerts enteroendocrinelcellssenselpsaftergutbarrierinjurytoenhanceglp1secretion AT dorienkiers enteroendocrinelcellssenselpsaftergutbarrierinjurytoenhanceglp1secretion AT jeanpaulpaisdebarros enteroendocrinelcellssenselpsaftergutbarrierinjurytoenhanceglp1secretion AT naigleguern enteroendocrinelcellssenselpsaftergutbarrierinjurytoenhanceglp1secretion AT jiriplesnik enteroendocrinelcellssenselpsaftergutbarrierinjurytoenhanceglp1secretion AT charlesthomas enteroendocrinelcellssenselpsaftergutbarrierinjurytoenhanceglp1secretion AT thibautbourgeois enteroendocrinelcellssenselpsaftergutbarrierinjurytoenhanceglp1secretion AT cornelishcdejong enteroendocrinelcellssenselpsaftergutbarrierinjurytoenhanceglp1secretion AT matthijskox enteroendocrinelcellssenselpsaftergutbarrierinjurytoenhanceglp1secretion AT incahrhundscheid enteroendocrinelcellssenselpsaftergutbarrierinjurytoenhanceglp1secretion AT naimakhtarkhan enteroendocrinelcellssenselpsaftergutbarrierinjurytoenhanceglp1secretion AT stephanemandard enteroendocrinelcellssenselpsaftergutbarrierinjurytoenhanceglp1secretion AT valeriedeckert enteroendocrinelcellssenselpsaftergutbarrierinjurytoenhanceglp1secretion AT peterpickkers enteroendocrinelcellssenselpsaftergutbarrierinjurytoenhanceglp1secretion AT danieljdrucker enteroendocrinelcellssenselpsaftergutbarrierinjurytoenhanceglp1secretion AT laurentlagrost enteroendocrinelcellssenselpsaftergutbarrierinjurytoenhanceglp1secretion AT jacquesgrober enteroendocrinelcellssenselpsaftergutbarrierinjurytoenhanceglp1secretion |