Sweet taste receptors in rat small intestine stimulate glucose absorption through apical GLUT2

Sweet taste receptors in rat small intestine stimulate glucose absorption through apical GLUT2
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DOI:
10.1113/jphysiol.2007.130906
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发表时间:
2007-07-01
影响因子:
5.5
通讯作者:
Kellett, George L.
Kellett, George L.
中科院分区:
医学1区
文献类型:
--
作者:
Mace, Oliver J.;Affleck, Julie;Kellett, George L.

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被引文献

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天然糖和人工甜味剂是由味蕾中的受体感知的。T2R苦味受体和T1R甜味受体通过g蛋白、α -gustducin和转导蛋白偶联,激活磷脂酶C β 2,增加细胞内钙浓度。肠刷细胞或孤立化学感觉细胞(SCCs)具有与舌味觉细胞相似的结构,并强烈表达α -味觉传导素。因此,在过去的十年中,有人提出刷细胞可能通过类似于味蕾的机制参与糖感知。我们在此提供了基于舌味觉感受器的肠道感觉系统的功能证据。Western blotting和免疫细胞化学显示,所有T1R成员均在大鼠空肠的重要位置表达,包括Paneth细胞、SCCs或肠细胞的顶膜;T1Rs彼此之间以及不同程度地与α -传导蛋白、转导蛋白或磷脂酶C β 2共定位。肠道葡萄糖吸收由两部分组成:一是经典的Na+-葡萄糖活性共转运途径,二是弥漫性的根尖GLUT2途径。人工甜味剂增加葡萄糖吸收的顺序是乙酰磺胺钾,类似于三氯蔗糖b>糖精,同时它们增加细胞内钙浓度的能力是平行的。刺激发生在几分钟内,顶端GLUT2增加,这与T1R1、T1R3和α -谷氨酰胺传导蛋白对T1R1、转导蛋白和磷脂酶C β 2的相互调节有关。我们观察到人造甜味剂具有营养活性,因为它们可以向功能性味觉接收系统发出信号,以增加膳食中糖的吸收,这对营养感知和营养治疗肥胖和糖尿病具有广泛的意义。
Natural sugars and artificial sweeteners are sensed by receptors in taste buds. T2R bitter and T1R sweet taste receptors are coupled through G-proteins, alpha-gustducin and transducin, to activate phospholipase C beta 2 and increase intracellular calcium concentration. Intestinal brush cells or solitary chemosensory cells (SCCs) have a structure similar to lingual taste cells and strongly express alpha-gustducin. It has therefore been suggested over the last decade that brush cells may participate in sugar sensing by a mechanism analogous to that in taste buds. We provide here functional evidence for an intestinal sensing system based on lingual taste receptors. Western blotting and immunocytochemistry revealed that all T1R members are expressed in rat jejunum at strategic locations including Paneth cells, SCCs or the apical membrane of enterocytes; T1Rs are colocalized with each other and with alpha-gustducin, transducin or phospholipase C beta 2 to different extents. Intestinal glucose absorption consists of two components: one is classical active Na+-glucose cotransport, the other is the diffusive apical GLUT2 pathway. Artificial sweeteners increase glucose absorption in the order acesulfame potassium similar to sucralose > saccharin, in parallel with their ability to increase intracellular calcium concentration. Stimulation occurs within minutes by an increase in apical GLUT2, which correlates with reciprocal regulation of T1R2, T1R3 and alpha-gustducin versus T1R1, transducin and phospholipase C beta 2. Our observation that artificial sweeteners are nutritionally active, because they can signal to a functional taste reception system to increase sugar absorption during a meal, has wide implications for nutrient sensing and nutrition in the treatment of obesity and diabetes.