title: Denatonium induces secretion of glucagon-like peptide-1 through activation of bitter taste receptor pathways.
abstract: OBJECTIVE
  This study was designed to ascertain whether human enteroendocrine cells express bitter taste receptors, and whether activation of these receptors with bitter-tasting ligands induces secretion of glucagon-like peptide-1 (GLP-1) and peptide YY (PYY).
  
  
  METHODS
  We used human enteroendocrine NCI-H716 cells, isolated duodenal segments from mice, and whole mice as our experimental systems for investigating stimuli and mechanisms underlying GLP-1- and PYY-stimulated release. We measured hormone levels by ELISA and determined bitter taste receptor expression by real-time quantitative PCR. We adopted a pharmacological approach using inhibitors and enhancers of downstream signalling pathways known to be involved in bitter taste transduction in taste bud cells to investigate these pathways in NCI-H716 cells.
  
  
  RESULTS
  Using a pharmacological approach, we identified signalling pathways triggered by the denatonium benzoate (DB)-activated bitter receptors. This involved activation of α-gustducin (Gαgust)-the specific G-protein subunit that is also present in taste bud cells-reduction of intracellular cAMP levels and enhancement of phospholipase C (PLC) activity, which ultimately led to increased intracellular calcium concentrations and hormone release. Gavage of DB, followed by gavage of glucose, to db/db mice stimulated GLP-1 and subsequent insulin secretion, leading to lower blood glucose levels.
  
  
  CONCLUSIONS
  Our study demonstrates that activation of gut-expressed bitter taste receptors stimulates GLP-1 secretion in a PLC-dependent manner. In diabetic mice, DB (a ligand of bitter taste receptor cells), when given via gavage, lowers blood glucose levels in diabetic mice after oral glucose administration, through increased secretion of GLP-1.
authors.affiliation: Department of Biochemistry, College of Korean Medicine, Kyung Hee University, Hoegi-Dong, Dongdaemun-Gu, Seoul, 130-701, Republic of Korea.
authors.forename: Ki-Suk
authors.initials: KS
authors.lastname: Kim
authors.forename: Josephine M
authors.initials: JM
authors.lastname: Egan
authors.forename: Hyeung-Jin
authors.initials: HJ
authors.lastname: Jang
mesh_terms: D000818:Animals; D002460:Cell Line; D000242:Cyclic AMP / Q000378:metabolism; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism*; D006801:Humans; D051379:Mice; D019894:Peptide YY / Q000378:metabolism; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology*; D060888:Real-Time Polymerase Chain Reaction; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D010738:Type C Phospholipases / Q000378:metabolism
chemical_list: D000644:Quaternary Ammonium Compounds; D043562:Receptors, G-Protein-Coupled; D019894:Peptide YY; C043414:denatonium; D052216:Glucagon-Like Peptide 1; D000242:Cyclic AMP; D010738:Type C Phospholipases