T1R3 and gustducin in gut sense sugars to regulate expression of Na+-glucose cotransporter 1
T1R3 and gustducin in gut sense sugars to regulate expression of Na+-glucose cotransporter 1
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DOI：
10.1073/pnas.0706678104
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发表时间：
2007-09-18
影响因子：
11.1
通讯作者：
Shirazi-Beechey, Soraya P.
中科院分区：
文献类型：
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作者：
Margolskee, Robert F.;Dyer, Jane;Shirazi-Beechey, Soraya P.
膳食糖通过钠依赖的葡萄糖转运体1(SGLT1)从肠腔转运到可吸收的肠细胞中。对这种蛋白质的调节对于向身体提供葡萄糖和避免肠道吸收不良很重要。尽管SGLT1的表达受管腔单糖的调节，但管腔葡萄糖传感器调节这一过程的机制尚不清楚。在这里，我们证明了甜味受体亚单位T1R3和味觉G蛋白Gustducin在肠道内分泌细胞中表达，是肠道糖感受和SGLT1基因和蛋白调节的基础。饮食中的糖和人工甜味剂增加了野生型小鼠SGLT1的mRNA和蛋白的表达，以及葡萄糖的吸收能力，但在缺乏T1R3或α-Gustducin的基因敲除小鼠中没有。人工甜味剂作用于肠内分泌GLUTag细胞上表达的甜味受体，刺激胃肠激素的分泌，与SGLT1上调有关。参与调节SGLT1表达的肠道表达的味觉信号元件可能为调节肠道对糖的吸收能力提供新的治疗靶点，对于预防和/或治疗吸收不良综合征以及糖尿病和肥胖等与饮食相关的疾病具有重要意义。
Dietary sugars are transported from the intestinal lumen into absorptive enterocytes by the sodium-dependent glucose transporter isoform 1 (SGLT1). Regulation of this protein is important for the provision of glucose to the body and avoidance of intestinal malabsorption. Although expression of SGLT1 is regulated by luminal monosaccharides, the luminal glucose sensor mediating this process was unknown. Here, we show that the sweet taste receptor subunit T1R3 and the taste G protein gustducin, expressed in enteroendocrine cells, underlie intestinal sugar sensing and regulation of SGLT1 mRNA and protein. Dietary sugar and artificial sweeteners increased SGLT1 mRNA and protein expression, and glucose absorptive capacity in wild-type mice, but not in knockout mice lacking T1R3 or alpha-gustducin. Artificial sweeteners, acting on sweet taste receptors expressed on enteroendocrine GLUTag cells, stimulated secretion of gut hormones implicated in SGLT1 upregulation. Gut-expressed taste signaling elements involved in regulating SGLT1 expression could provide novel therapeutic targets for modulating the gut's capacity to absorb sugars, with implications for the prevention and/or treatment of malabsorption syndromes and diet-related disorders including diabetes and obesity.