Moran Andrew W, Alrammahi Miran, Daly Kristian, Weatherburn Darren, Ionescu Catherine, Blanchard Alexandra, Shirazi-Beechey Soraya P
Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool L69 7ZJ, UK.
Department of Physiology, Biochemistry and Pharmacology, College of Veterinary Medicine, University of Al-Qadisiyah, Al-Diwaniyah 58002, Iraq.
Nutrients. 2025 Apr 30;17(9):1547. doi: 10.3390/nu17091547.
Dietary glucose is transported across the intestinal absorptive cell into the systemic circulation by the apically located Na-dependent glucose transporter 1 (SGLT1, ) and basally residing Na-independent glucose transporter 2 (GLUT2, ). Whilst recent experimental evidence has shown that sensing of sweet compounds by the gut-expressed sweet taste receptor T1R2-T1R3 and glucagon-like peptide-2 receptor signalling are components of the pathway controlling SGLT1 expression, little is known about the mechanisms involved in the regulation of GLUT2. In this study, we tested the hypothesis that T1R2-T1R3 and its downstream signalling pathway participate in the regulation of intestinal GLUT2. : We used in vivo and in vitro approaches employing a weaning pig model, a heterologous expression assay, and knockout mice for elucidating the regulation of GLUT2 by luminal sugars. : A plant-based sweetener formulation included in piglets' diet led to a marked increase in GLUT2 expression in piglets' intestine, compared to controls. The sweeteners that do not activate pig T1R2-T1R3 failed to upregulate GLUT2. There was a significant increase in GLUT2 expression when the sweetener sucralose, which activates T1R2-T1R3, was included in the drinking water of wild-type mice. However, in knockout mice, in which the genes for the sweet receptor subunit T1R3 and the associated G-protein gustducin were deleted, there was no upregulation of GLUT2 expression in response to sucralose supplementation. There was a notable increase in GLUT2 expression in wild-type mice fed a high-carbohydrate diet compared to when maintained on a low-carbohydrate diet. However, in GLP-2 receptor knockout mice kept on the high-carbohydrate diet, there was no enhancement in GLUT2 expression. : The experimental evidence suggests that luminal sweet sensing via T1R2-T1R3 and the enteroendocrine-derived GLP-2 are constituents of the regulatory pathway controlling GLUT2 expression.
膳食葡萄糖通过位于顶端的钠依赖性葡萄糖转运蛋白1（SGLT1）跨肠吸收细胞进入体循环，并通过位于基底的非钠依赖性葡萄糖转运蛋白2（GLUT2）进行转运。虽然最近的实验证据表明，肠道表达的甜味受体T1R2-T1R3对甜味化合物的感知以及胰高血糖素样肽-2受体信号传导是控制SGLT1表达途径的组成部分，但对于GLUT2调控所涉及的机制知之甚少。在本研究中，我们检验了T1R2-T1R3及其下游信号通路参与肠道GLUT2调控的假说。：我们采用体内和体外方法，利用断奶仔猪模型、异源表达试验以及基因敲除小鼠，以阐明管腔糖类对GLUT2的调控。：与对照组相比，仔猪日粮中添加的一种植物性甜味剂配方导致仔猪肠道中GLUT2表达显著增加。未激活猪T1R2-T1R3的甜味剂未能上调GLUT2。当激活T1R2-T1R3的甜味剂三氯蔗糖添加到野生型小鼠的饮用水中时，GLUT2表达显著增加。然而，在甜味受体亚基T1R3和相关G蛋白味导素基因被敲除的基因敲除小鼠中，补充三氯蔗糖后GLUT2表达没有上调。与维持低碳水化合物饮食相比，喂食高碳水化合物饮食的野生型小鼠GLUT2表达显著增加。然而，维持高碳水化合物饮食的胰高血糖素样肽-2受体基因敲除小鼠中，GLUT2表达没有增强。：实验证据表明，通过T1R2-T1R3的管腔甜味感知以及肠内分泌来源的胰高血糖素样肽-2是控制GLUT2表达的调控途径的组成部分。
