title: Apelin targets gut contraction to control glucose metabolism via the brain.
abstract: The gut-brain axis is considered as a major regulatory checkpoint in the control of glucose homeostasis. The detection of nutrients and/or hormones in the duodenum informs the hypothalamus of the host's nutritional state. This process may occur via hypothalamic neurons modulating central release of nitric oxide (NO), which in turn controls glucose entry into tissues. The enteric nervous system (ENS) modulates intestinal contractions in response to various stimuli, but the importance of this interaction in the control of glucose homeostasis via the brain is unknown. We studied whether apelin, a bioactive peptide present in the gut, regulates ENS-evoked contractions, thereby identifying a new physiological partner in the control of glucose utilisation via the hypothalamus.
  
  
  
  We measured the effect of apelin on electrical and mechanical duodenal responses via telemetry probes and isotonic sensors in normal and obese/diabetic mice. Changes in hypothalamic NO release, in response to duodenal contraction modulated by apelin, were evaluated in real time with specific amperometric probes. Glucose utilisation in tissues was measured with orally administrated radiolabeled glucose.
  
  
  
  In normal and obese/diabetic mice, glucose utilisation is improved by the decrease of ENS/contraction activities in response to apelin, which generates an increase in hypothalamic NO release. As a consequence, glucose entry is significantly increased in the muscle.
  
  
  
  Here, we identify a novel mode of communication between the intestine and the hypothalamus that controls glucose utilisation. Moreover, our data identified oral apelin administration as a novel potential target to treat metabolic disorders.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM), U1048, Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Toulouse Cedex 4, France.|NeuroMicrobiota, European Associated Laboratory (EAL) INSERM/UCL.|Université Paul Sabatier, Toulouse, France.
authors.forename: Audren
authors.initials: A
authors.lastname: Fournel
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM), U1048, Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Toulouse Cedex 4, France.|NeuroMicrobiota, European Associated Laboratory (EAL) INSERM/UCL.|Université Paul Sabatier, Toulouse, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Drougard
authors.affiliation: NeuroMicrobiota, European Associated Laboratory (EAL) INSERM/UCL.|Université Catholique de Louvain (UCL), Louvain Drug Research Institute, LDRI, Metabolism and Nutrition research group, WELBIO (Walloon Excellence in Life sciences and BIOtechnology), Brussels, Belgium.
authors.forename: Thibaut
authors.initials: T
authors.lastname: Duparc
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM), U1048, Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Toulouse Cedex 4, France.|NeuroMicrobiota, European Associated Laboratory (EAL) INSERM/UCL.|Université Paul Sabatier, Toulouse, France.
authors.forename: Alysson
authors.initials: A
authors.lastname: Marlin
authors.affiliation: Visceral Pain Group, Centre for Nutrition and Gastrointestinal Diseases, Discipline of Medicine, University of Adelaide, South Australia Health and Medical Research Institute (SAHMRI), Adelaide, South Australia, Australia.|Department of Gastroenterology and Hepatology, Royal Adelaide Hospital, Adelaide, South Australia, Australia.|Discipline of Physiology, Faculty of Health Sciences, The University of Adelaide, Adelaide, South Australia, Australia.
authors.forename: Stuart M
authors.initials: SM
authors.lastname: Brierley
authors.affiliation: Visceral Pain Group, Centre for Nutrition and Gastrointestinal Diseases, Discipline of Medicine, University of Adelaide, South Australia Health and Medical Research Institute (SAHMRI), Adelaide, South Australia, Australia.
authors.forename: Joel
authors.initials: J
authors.lastname: Castro
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM), U1048, Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Toulouse Cedex 4, France.|NeuroMicrobiota, European Associated Laboratory (EAL) INSERM/UCL.|Université Paul Sabatier, Toulouse, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Le-Gonidec
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM), U1037, Centre de Recherches en Cancérologie de Toulouse (CRCT), CHU Rangueil, Toulouse, Cedex 4, France.
authors.forename: Bernard
authors.initials: B
authors.lastname: Masri
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM), U1048, Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Toulouse Cedex 4, France.|NeuroMicrobiota, European Associated Laboratory (EAL) INSERM/UCL.|Université Paul Sabatier, Toulouse, France.
authors.forename: André
authors.initials: A
authors.lastname: Colom
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM), U1048, Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Toulouse Cedex 4, France.|NeuroMicrobiota, European Associated Laboratory (EAL) INSERM/UCL.|Université Paul Sabatier, Toulouse, France.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Lucas
authors.affiliation: Université Paul Sabatier, Toulouse, France.|Institut National de la Santé et de la Recherche Médicale (INSERM), U1043, Centre de Physiopathologie de Toulouse Purpan (CPTP), CHU Purpan, Toulouse, Cedex 03, France.
authors.forename: Perrine
authors.initials: P
authors.lastname: Rousset
authors.affiliation: Université Paul Sabatier, Toulouse, France.|Institut National de la Santé et de la Recherche Médicale (INSERM), U1043, Centre de Physiopathologie de Toulouse Purpan (CPTP), CHU Purpan, Toulouse, Cedex 03, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Cenac
authors.affiliation: Université Paul Sabatier, Toulouse, France.|Institut National de la Santé et de la Recherche Médicale (INSERM), U1043, Centre de Physiopathologie de Toulouse Purpan (CPTP), CHU Purpan, Toulouse, Cedex 03, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Vergnolle
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM), U1048, Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Toulouse Cedex 4, France.|NeuroMicrobiota, European Associated Laboratory (EAL) INSERM/UCL.|Université Paul Sabatier, Toulouse, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Valet
authors.affiliation: NeuroMicrobiota, European Associated Laboratory (EAL) INSERM/UCL.|Université Catholique de Louvain (UCL), Louvain Drug Research Institute, LDRI, Metabolism and Nutrition research group, WELBIO (Walloon Excellence in Life sciences and BIOtechnology), Brussels, Belgium.
authors.forename: Patrice D
authors.initials: PD
authors.lastname: Cani
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM), U1048, Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Toulouse Cedex 4, France.|NeuroMicrobiota, European Associated Laboratory (EAL) INSERM/UCL.|Université Paul Sabatier, Toulouse, France.
authors.forename: Claude
authors.initials: C
authors.lastname: Knauf
mesh_terms: D054392:Adipokines / Q000494:pharmacology*; D000818:Animals; D000073861:Apelin; D015374:Biosensing Techniques; D003920:Diabetes Mellitus / Q000503:physiopathology; D004386:Duodenum / Q000187:drug effects / Q000378:metabolism; D017615:Enteric Nervous System / Q000187:drug effects* / Q000502:physiology; D005769:Gastrointestinal Motility / Q000187:drug effects; D005947:Glucose / Q000378:metabolism*; D006706:Homeostasis; D007031:Hypothalamus / Q000187:drug effects* / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000502:physiology; D009569:Nitric Oxide / Q000378:metabolism; D009765:Obesity / Q000503:physiopathology; D013686:Telemetry
chemical_list: D054392:Adipokines; D000073861:Apelin; C402826:Apln protein, mouse; D036341:Intercellular Signaling Peptides and Proteins; D009569:Nitric Oxide; D005947:Glucose
keywords: ENTERIC NERVOUS SYSTEM; GASTROINTESTINAL PHYSIOLOGY; GLUCOSE METABOLISM; GUT HORMONES; OBESITY