T1R2 receptor-mediated glucose sensing in the upper intestine potentiates glucose absorption through activation of local regulatory pathways.
T1R2 receptor-mediated glucose sensing in the upper intestine potentiates glucose absorption through activation of local regulatory pathways.
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DOI：
10.1016/j.molmet.2018.08.009
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发表时间：
2018-11
影响因子：
8.1
通讯作者：
Kyriazis GA
中科院分区：
文献类型：
--
作者：
Smith K;Karimian Azari E;LaMoia TE;Hussain T;Vargova V;Karolyi K;Veldhuis PP;Arnoletti JP;de la Fuente SG;Pratley RE;Osborne TF;Kyriazis GA
除了味蕾，甜味受体（STR; T1 R2/T1 R3）也在肠内分泌细胞上表达，它们调节肠道肽分泌，但它们在肠道内的调节功能在很大程度上是未知的。使用T1 R2基因敲除（KO）小鼠，我们评估了STR在体内和离体完整肠道制剂中调节葡萄糖吸收的作用。STR信号传导增强肠道葡萄糖吸收的速率，特别是响应于摄取富含葡萄糖的膳食。这些作用是通过调节GLUT 2转运蛋白转运至肠上皮细胞顶膜而特异性介导的。GLUT 2易位和葡萄糖转运依赖于胰高血糖素样肽2（GLP-2）分泌和随后的肠神经元激活，并具有特异性。最后，高蔗糖喂养野生型小鼠诱导肠道中STR的快速下调，导致葡萄糖吸收减少。我们的研究表明，STR已经进化到通过调节葡萄糖的转运来调节葡萄糖的吸收，并防止由于摄入高水平的糖而导致的加重的高血糖症的发展。肠T1 R2受体增强体内和离体葡萄糖吸收。STR的药理学抑制降低了人肠道制剂中的葡萄糖通量。T1 R2依赖于肠上皮细胞中的GLUT 2活性调节葡萄糖吸收。GLP-2通过激活肠神经元介导T1 R2信号传导的作用。高蔗糖饮食快速下调STR，导致葡萄糖吸收减少。
Beyond the taste buds, sweet taste receptors (STRs; T1R2/T1R3) are also expressed on enteroendocrine cells, where they regulate gut peptide secretion but their regulatory function within the intestine is largely unknown. Using T1R2-knock out (KO) mice we evaluated the role of STRs in the regulation of glucose absorption in vivo and in intact intestinal preparations ex vivo. STR signaling enhances the rate of intestinal glucose absorption specifically in response to the ingestion of a glucose-rich meal. These effects were mediated specifically by the regulation of GLUT2 transporter trafficking to the apical membrane of enterocytes. GLUT2 translocation and glucose transport was dependent and specific to glucagon-like peptide 2 (GLP-2) secretion and subsequent intestinal neuronal activation. Finally, high-sucrose feeding in wild-type mice induced rapid downregulation of STRs in the gut, leading to reduced glucose absorption. Our studies demonstrate that STRs have evolved to modulate glucose absorption via the regulation of its transport and to prevent the development of exacerbated hyperglycemia due to the ingestion of high levels of sugars. The intestinal T1R2 receptor enhances glucose absorption in vivo and ex vivo. Pharmacological inhibition of STRs reduces glucose flux in human intestinal preparations. T1R2 regulates glucose absorption dependent on GLUT2 activity in enterocytes. GLP-2 mediates the effects of T1R2 signaling through activation of enteric neurons. High sucrose diet rapidly downregulates STRs leading to reduced glucose absorption.
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影响因子：
16.2
作者：
Brown RJ;Walter M;Rother KI
通讯作者：
Rother KI
影响因子：
4.6
作者：
Herrera Moro Chao D;Argmann C;Van Eijk M;Boot RG;Ottenhoff R;Van Roomen C;Foppen E;Siljee JE;Unmehopa UA;Kalsbeek A;Aerts JM
通讯作者：
Aerts JM
影响因子：
7
作者：
DUEE, PH;DARCYVRILLON, B;MOREL, MT
通讯作者：
MOREL, MT
影响因子：
7.3
作者：
HEADING, RC;NIMMO, J;TOTHILL, P
通讯作者：
TOTHILL, P
肠道甜味受体在调节人体 GLP-1、PYY 和 CCK 释放中的作用
DOI：
10.1152/ajpendo.00077.2011
发表时间：
2011-08-01
影响因子：
5.1
作者：
Gerspach, A. C.;Steinert, R. E.;Beglinger, C.
通讯作者：
Beglinger, C.