title: A sweet taste receptor-dependent mechanism of glucosensing in hypothalamic tanycytes.
abstract: Hypothalamic tanycytes are glial-like glucosensitive cells that contact the cerebrospinal fluid of the third ventricle, and send processes into the hypothalamic nuclei that control food intake and body weight. The mechanism of tanycyte glucosensing remains undetermined. While tanycytes express the components associated with the glucosensing of the pancreatic β cell, they respond to nonmetabolisable glucose analogues via an ATP receptor-dependent mechanism. Here, we show that tanycytes in rodents respond to non-nutritive sweeteners known to be ligands of the sweet taste (Tas1r2/Tas1r3) receptor. The initial sweet tastant-evoked response, which requires the presence of extracellular Ca2+, leads to release of ATP and a larger propagating Ca2+response mediated by P2Y1 receptors. In Tas1r2 null mice the proportion of glucose nonresponsive tanycytes was greatly increased in these mice, but a subset of tanycytes retained an undiminished sensitivity to glucose. Our data demonstrate that the sweet taste receptor mediates glucosensing in about 60% of glucosensitive tanycytes while the remaining 40% of glucosensitive tanycytes use some other, as yet unknown mechanism.
authors.affiliation: School of Life Sciences, University of Warwick, Coventry, United Kingdom.
authors.forename: Heather
authors.initials: H
authors.lastname: Benford
authors.affiliation: School of Life Sciences, University of Warwick, Coventry, United Kingdom.
authors.forename: Matei
authors.identifier: 0000-0003-2313-2770
authors.initials: M
authors.lastname: Bolborea
authors.affiliation: School of Life Sciences, University of Warwick, Coventry, United Kingdom.
authors.forename: Eric
authors.initials: E
authors.lastname: Pollatzek
authors.affiliation: Department of Molecular Genetics, German Institute of Human Nutrition Potsdam-Rehbruecke, Arthur-Scheunert-Allee 114-116, Nuthetal, 14558, Germany.
authors.forename: Kristina
authors.initials: K
authors.lastname: Lossow
authors.affiliation: Transgenic Animal Unit, University Medical Center Hamburg-Eppendorf, Martinistr. 52, Hamburg, 20246, Germany.
authors.forename: Irm
authors.initials: I
authors.lastname: Hermans-Borgmeyer
authors.affiliation: School of Physiology and Pharmacology, University of Bristol, United Kingdom.
authors.forename: Beihui
authors.initials: B
authors.lastname: Liu
authors.affiliation: Department of Molecular Genetics, German Institute of Human Nutrition Potsdam-Rehbruecke, Arthur-Scheunert-Allee 114-116, Nuthetal, 14558, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Meyerhof
authors.affiliation: School of Physiology and Pharmacology, University of Bristol, United Kingdom.
authors.forename: Sergey
authors.identifier: 0000-0002-1824-1764
authors.initials: S
authors.lastname: Kasparov
authors.affiliation: School of Life Sciences, University of Warwick, Coventry, United Kingdom.
authors.forename: Nicholas
authors.identifier: 0000-0003-2196-2949
authors.initials: N
authors.lastname: Dale
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D005260:Female; D005947:Glucose / Q000378:metabolism*; D007031:Hypothalamus / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D009457:Neuroglia / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000172:deficiency; D058472:Receptors, Purinergic P2Y1 / Q000378:metabolism; D013649:Taste / Q000502:physiology*
chemical_list: D043562:Receptors, G-Protein-Coupled; D058472:Receptors, Purinergic P2Y1; C431926:taste receptors, type 1; D005947:Glucose; D002118:Calcium
keywords: energy balance; hypothalamus; tanycyte