title: Gut-expressed gustducin and taste receptors regulate secretion of glucagon-like peptide-1.
abstract: Glucagon-like peptide-1 (GLP-1), released from gut endocrine L cells in response to glucose, regulates appetite, insulin secretion, and gut motility. How glucose given orally, but not systemically, induces GLP-1 secretion is unknown. We show that human duodenal L cells express sweet taste receptors, the taste G protein gustducin, and several other taste transduction elements. Mouse intestinal L cells also express alpha-gustducin. Ingestion of glucose by alpha-gustducin null mice revealed deficiencies in secretion of GLP-1 and the regulation of plasma insulin and glucose. Isolated small bowel and intestinal villi from alpha-gustducin null mice showed markedly defective GLP-1 secretion in response to glucose. The human L cell line NCI-H716 expresses alpha-gustducin, taste receptors, and several other taste signaling elements. GLP-1 release from NCI-H716 cells was promoted by sugars and the noncaloric sweetener sucralose, and blocked by the sweet receptor antagonist lactisole or siRNA for alpha-gustducin. We conclude that L cells of the gut "taste" glucose through the same mechanisms used by taste cells of the tongue. Modulating GLP-1 secretion in gut "taste cells" may provide an important treatment for obesity, diabetes and abnormal gut motility.
authors.affiliation: National Institute on Aging/National Institutes of Health, 5600 Nathan Shock Drive, Baltimore, MD 21224, USA.
authors.forename: Hyeung-Jin
authors.initials: HJ
authors.lastname: Jang
authors.forename: Zaza
authors.initials: Z
authors.lastname: Kokrashvili
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Theodorakis
authors.forename: Olga D
authors.initials: OD
authors.lastname: Carlson
authors.forename: Byung-Joon
authors.initials: BJ
authors.lastname: Kim
authors.forename: Jie
authors.initials: J
authors.lastname: Zhou
authors.forename: Hyeon Ho
authors.initials: HH
authors.lastname: Kim
authors.forename: Xiangru
authors.initials: X
authors.lastname: Xu
authors.forename: Sic L
authors.initials: SL
authors.lastname: Chan
authors.forename: Magdalena
authors.initials: M
authors.lastname: Juhaszova
authors.forename: Michel
authors.initials: M
authors.lastname: Bernier
authors.forename: Bedrich
authors.initials: B
authors.lastname: Mosinger
authors.forename: Robert F
authors.initials: RF
authors.lastname: Margolskee
authors.forename: Josephine M
authors.initials: JM
authors.lastname: Egan
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004386:Duodenum / Q000378:metabolism*; D019858:Enteroendocrine Cells / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism; D020962:Heterotrimeric GTP-Binding Proteins / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*
chemical_list: D043562:Receptors, G-Protein-Coupled; C431926:taste receptors, type 1; D052216:Glucagon-Like Peptide 1; C524407:GNAT3 protein, mouse; D020962:Heterotrimeric GTP-Binding Proteins; D005947:Glucose