A sweet taste receptor-dependent mechanism of glucosensing in hypothalamic tanycytes

Heather Benford, Matei Bolborea, Eric Pollatzek, Kristina Lossow, Irm Hermans-Borgmeyer, Beihui Liu, Wolfgang Meyerhof, Sergey Kasparov, Nicholas Dale*

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

33 Citations (Scopus)
366 Downloads (Pure)

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.

Original languageEnglish
Pages (from-to)773-789
Number of pages17
JournalGlia
Volume65
Issue number5
Early online date16 Feb 2017
DOIs
Publication statusPublished - 1 May 2017

Keywords

  • energy balance
  • hypothalamus
  • tanycyte

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