title: Insulin-like peptide 5 is an orexigenic gastrointestinal hormone.
abstract: The gut endocrine system is emerging as a central player in the control of appetite and glucose homeostasis, and as a rich source of peptides with therapeutic potential in the field of diabetes and obesity. In this study we have explored the physiology of insulin-like peptide 5 (Insl5), which we identified as a product of colonic enteroendocrine L-cells, better known for their secretion of glucagon-like peptide-1 and peptideYY. i.p. Insl5 increased food intake in wild-type mice but not mice lacking the cognate receptor Rxfp4. Plasma Insl5 levels were elevated by fasting or prolonged calorie restriction, and declined with feeding. We conclude that Insl5 is an orexigenic hormone released from colonic L-cells, which promotes appetite during conditions of energy deprivation.
authors.affiliation: Takeda Cambridge Ltd., Cambridge CB4 0PA, United Kingdom;
authors.forename: Johannes
authors.initials: J
authors.lastname: Grosse
authors.affiliation: Takeda Cambridge Ltd., Cambridge CB4 0PA, United Kingdom;
authors.forename: Helen
authors.initials: H
authors.lastname: Heffron
authors.affiliation: Core Biochemical Assay Laboratory, Addenbrooke's Hospital, Cambridge CB2 0QQ, United Kingdom;
authors.forename: Keith
authors.initials: K
authors.lastname: Burling
authors.affiliation: Florey Institute of Neuroscience and Mental Health, and School of Chemistry, University of Melbourne, Melbourne, VIC 3010, Australia;
authors.forename: Mohammed
authors.initials: M
authors.lastname: Akhter Hossain
authors.affiliation: Cambridge Institute for Medical Research, University of Cambridge, Cambridge CB2 0XY, United Kingdom;
authors.forename: Abdella M
authors.initials: AM
authors.lastname: Habib
authors.affiliation: Cambridge Institute for Medical Research, University of Cambridge, Cambridge CB2 0XY, United Kingdom;
authors.forename: Gareth J
authors.initials: GJ
authors.lastname: Rogers
authors.affiliation: Cambridge Institute for Medical Research, University of Cambridge, Cambridge CB2 0XY, United Kingdom;Metabolic Research Laboratories and MRC Metabolic Diseases Unit, Institute of Metabolic Science, University of Cambridge, Cambridge CB2 0QQ, United Kingdom;
authors.forename: Paul
authors.initials: P
authors.lastname: Richards
authors.affiliation: Metabolic Research Laboratories and MRC Metabolic Diseases Unit, Institute of Metabolic Science, University of Cambridge, Cambridge CB2 0QQ, United Kingdom;
authors.forename: Rachel
authors.initials: R
authors.lastname: Larder
authors.affiliation: Metabolic Research Laboratories and MRC Metabolic Diseases Unit, Institute of Metabolic Science, University of Cambridge, Cambridge CB2 0QQ, United Kingdom;
authors.forename: Debra
authors.initials: D
authors.lastname: Rimmington
authors.affiliation: Cambridge Institute for Medical Research, University of Cambridge, Cambridge CB2 0XY, United Kingdom;Metabolic Research Laboratories and MRC Metabolic Diseases Unit, Institute of Metabolic Science, University of Cambridge, Cambridge CB2 0QQ, United Kingdom;
authors.forename: Alice A
authors.initials: AA
authors.lastname: Adriaenssens
authors.affiliation: Takeda Cambridge Ltd., Cambridge CB4 0PA, United Kingdom;
authors.forename: Laura
authors.initials: L
authors.lastname: Parton
authors.affiliation: Takeda Cambridge Ltd., Cambridge CB4 0PA, United Kingdom;
authors.forename: Justin
authors.initials: J
authors.lastname: Powell
authors.affiliation: Frimorfo Ltd., 1723 Fribourg, Switzerland;
authors.forename: Matteo
authors.initials: M
authors.lastname: Binda
authors.affiliation: Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge CB2 3EG, United Kingdom;
authors.forename: William H
authors.initials: WH
authors.lastname: Colledge
authors.affiliation: Takeda Cambridge Ltd., Cambridge CB4 0PA, United Kingdom;
authors.forename: Joanne
authors.initials: J
authors.lastname: Doran
authors.affiliation: Takeda Pharmaceutical Co. Ltd., Osaka, Japan; and.
authors.forename: Yukio
authors.initials: Y
authors.lastname: Toyoda
authors.affiliation: Florey Institute of Neuroscience and Mental Health, and School of Chemistry, University of Melbourne, Melbourne, VIC 3010, Australia;
authors.forename: John D
authors.initials: JD
authors.lastname: Wade
authors.affiliation: British Columbia Cancer Agency Branch, Vancouver, Canada V5Z 1L3.
authors.forename: Samuel
authors.initials: S
authors.lastname: Aparicio
authors.affiliation: Takeda Cambridge Ltd., Cambridge CB4 0PA, United Kingdom;
authors.forename: Mark B L
authors.initials: MB
authors.lastname: Carlton
authors.affiliation: Metabolic Research Laboratories and MRC Metabolic Diseases Unit, Institute of Metabolic Science, University of Cambridge, Cambridge CB2 0QQ, United Kingdom;
authors.forename: Anthony P
authors.initials: AP
authors.lastname: Coll
authors.affiliation: Cambridge Institute for Medical Research, University of Cambridge, Cambridge CB2 0XY, United Kingdom;Metabolic Research Laboratories and MRC Metabolic Diseases Unit, Institute of Metabolic Science, University of Cambridge, Cambridge CB2 0QQ, United Kingdom;
authors.forename: Frank
authors.initials: F
authors.lastname: Reimann
authors.affiliation: Metabolic Research Laboratories and MRC Metabolic Diseases Unit, Institute of Metabolic Science, University of Cambridge, Cambridge CB2 0QQ, United Kingdom; so104@medschl.cam.ac.uk.
authors.forename: Stephen
authors.initials: S
authors.lastname: O'Rahilly
authors.affiliation: Cambridge Institute for Medical Research, University of Cambridge, Cambridge CB2 0XY, United Kingdom;Metabolic Research Laboratories and MRC Metabolic Diseases Unit, Institute of Metabolic Science, University of Cambridge, Cambridge CB2 0QQ, United Kingdom;
authors.forename: Fiona M
authors.initials: FM
authors.lastname: Gribble
mesh_terms: D000818:Animals; D003106:Colon / Q000378:metabolism*; D004435:Eating / Q000187:drug effects* / Q000502:physiology*; D019858:Enteroendocrine Cells / Q000378:metabolism*; D005260:Female; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism; D006801:Humans; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D036361:Peptide Hormones / Q000378:metabolism* / Q000494:pharmacology*; D019894:Peptide YY / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D018000:Receptors, Peptide / Q000378:metabolism
chemical_list: C121388:Insl5 protein, mouse; D036361:Peptide Hormones; C480239:RXFP4 protein, human; C568363:RXFP4 protein, mouse; D043562:Receptors, G-Protein-Coupled; D018000:Receptors, Peptide; D019894:Peptide YY; D052216:Glucagon-Like Peptide 1