A sweet taste receptor-dependent mechanism of glucosensing in hypothalamic tanycytes.
A sweet taste receptor-dependent mechanism of glucosensing in hypothalamic tanycytes.
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作者：
Benford H;Bolborea M;Pollatzek E;Lossow K;Hermans-Borgmeyer I;Liu B;Meyerhof W;Kasparov S;Dale N
下丘脑单细胞是神经胶质样葡萄糖敏感细胞，接触第三脑室的脑脊液，并将过程发送到控制食物摄入和体重的下丘脑核团。单细胞葡萄糖传感的机制尚未确定。虽然单细胞表达与胰腺 β 细胞葡萄糖传感相关的成分，但它们通过 ATP 受体依赖性机制对不可代谢的葡萄糖类似物做出反应。在这里，我们发现啮齿类动物的单细胞对已知为甜味 (Tas1r2/Tas1r3) 受体配体的非营养性甜味剂有反应。最初的甜味促味剂诱发的反应需要细胞外 Ca2+ 的存在，导致 ATP 的释放和 P2Y1 受体介导的更大的传播 Ca2+ 反应。在 Tas1r2 缺失的小鼠中，葡萄糖无反应性单胞的比例大大增加，但单胞的一个子集保留了对葡萄糖的不减弱的敏感性。我们的数据表明，甜味受体在约 60% 的葡萄糖敏感性单细胞中介导葡萄糖感应，而其余 40% 的葡萄糖敏感性单细胞则使用一些其他尚未可知的机制。
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.