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A sweet taste receptor-dependent mechanism of glucosensing in hypothalamic tanycytes
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Benford, Heather Elizabeth, Bolborea, Matei, Pollatzek, Eric, Lossow, Kristina, Hermans-Borgmeyer, Irm, Liu, Beihui, Meyerhof, Wolfgang, Kasparov, Sergey and Dale, Nicholas (2017) A sweet taste receptor-dependent mechanism of glucosensing in hypothalamic tanycytes. Glia, 65 (5). pp. 773-789. doi:10.1002/glia.23125
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Official URL: http://dx.doi.org/10.1002/glia.23125
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.
| Item Type: | Journal Article | |||||||||
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| Subjects: | Q Science > QP Physiology | |||||||||
| Divisions: | Faculty of Science > Life Sciences (2010- ) Faculty of Medicine > Warwick Medical School |
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| Library of Congress Subject Headings (LCSH): | Hypothalamus -- Physiological aspects, Glucose, Cerebrospinal fluid | |||||||||
| Journal or Publication Title: | Glia | |||||||||
| Publisher: | John Wiley & Sons, Inc. | |||||||||
| ISSN: | 0894-1491 | |||||||||
| Official Date: | May 2017 | |||||||||
| Dates: |
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| Volume: | 65 | |||||||||
| Number: | 5 | |||||||||
| Page Range: | pp. 773-789 | |||||||||
| DOI: | 10.1002/glia.23125 | |||||||||
| Status: | Peer Reviewed | |||||||||
| Publication Status: | Published | |||||||||
| Access rights to Published version: | Open Access | |||||||||
| Funder: | Medical Research Council (Great Britain) (MRC) | |||||||||
| Grant number: | MR/J003786/1, MR/L020661/1 | |||||||||
| RIOXX Funder/Project Grant: |
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