title: The Sweetener-Sensing Mechanisms of the Ghrelin Cell.
abstract: Carbohydrate administration decreases plasma levels of the 'hunger hormone' ghrelin. The ghrelin cell is co-localized with the sweet taste receptor subunit, TAS1R3, and the gustatory G-protein, gustducin, both involved in the sensing of sweeteners by entero-endocrine cells. This study investigated the role of gustducin-mediated sweet taste receptor signaling on ghrelin secretion in a gastric ghrelinoma cell line, tissue segments and mice. The monosaccharide d-glucose and low-intensity sweetener oligofructose (OFS) decreased (p< 0.001) ghrelin secretion while the high-intensity sweetener sucralose increased (p< 0.001) ghrelin secretion in vitro. These effects were not mediated via the sweet taste receptor or glucose transporters (the sodium-dependent glucose cotransporter SGLT-1 and GLUT2). The effect of these compounds was mimicked ex vivo in gastric and jejunal segments from both wild type (WT) and α-gustducin knockout (α-gust-/-) mice. In vivo, the sensing of d-glucose was polarized since intragastric but not intravenous administration of d-glucose decreased (p< 0.05) ghrelin levels in an α-gustducin independent manner which involved inhibition of duodenal ghrelin release. In contrast, neither OFS nor sucralose affected ghrelin secretion in vivo. In conclusion, α-gustducin-mediated sweet taste receptor signaling does not play a functional role in the sensing of carbohydrates, or low- or high-intensity sweeteners by the ghrelin cell.
authors.affiliation: Gut Peptide Lab, Translational Research Center for Gastrointestinal Disorders (TARGID), University of Leuven-KU Leuven, 3000 Leuven, Belgium. sandra.steensels@kuleuven.be.
authors.forename: Sandra
authors.initials: S
authors.lastname: Steensels
authors.affiliation: Gut Peptide Lab, Translational Research Center for Gastrointestinal Disorders (TARGID), University of Leuven-KU Leuven, 3000 Leuven, Belgium. laurien.vancleef@kuleuven.be.
authors.forename: Laurien
authors.initials: L
authors.lastname: Vancleef
authors.affiliation: Gut Peptide Lab, Translational Research Center for Gastrointestinal Disorders (TARGID), University of Leuven-KU Leuven, 3000 Leuven, Belgium. inge.depoortere@kuleuven.be.
authors.forename: Inge
authors.initials: I
authors.lastname: Depoortere
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D005753:Gastric Mucosa / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology; D054439:Ghrelin / Q000378:metabolism*; D007583:Jejunum / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012333:RNA, Messenger; D015398:Signal Transduction; D013549:Sweetening Agents / Q000378:metabolism*; D015293:Transducin / Q000378:metabolism
chemical_list: D054439:Ghrelin; D012333:RNA, Messenger; D013549:Sweetening Agents; C075192:gustducin; D015293:Transducin
keywords: ghrelin; glucose; gustducin; sweet taste receptor; sweeteners