Taste cell-expressed α-glucosidase enzymes contribute to gustatory responses to disaccharides
Taste cell-expressed α-glucosidase enzymes contribute to gustatory responses to disaccharides
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DOI：
10.1073/pnas.1520843113
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发表时间：
2016-05-24
影响因子：
11.1
通讯作者：
Margolskee, Robert F.
中科院分区：
文献类型：
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作者：
Sukumaran, Sunil K.;Yee, Karen K.;Margolskee, Robert F.
哺乳动物味觉细胞中对糖和非热量甜味剂的主要甜味感受器是1型味觉受体2和3的异构体组合(T1R2+T1R3，由Tas1r2和Tas1r3基因编码)。然而，在缺乏T1R2+T1R3的情况下(例如，在Tas1r3KO小鼠中)，动物仍然对糖产生反应，这证明存在T1R不依赖于T1R的检测机制(S)。我们之前的研究发现，几种葡萄糖转运体(GLUTS)、钠葡萄糖共转运体1(SGLT1)和ATP门控K+(K-ATP)代谢传感器与T1R3在同一味觉细胞中优先表达，这为T1R不依赖糖和甜味剂的检测提供了潜在的解释：对糖和甜味剂反应的甜味细胞可能包含一条T1R依赖(T1R2+T1R3)的甜感通路来检测糖和非热量甜味剂，以及一条T1R不依赖的(Gluts，SGLT1，K-ATP)途径来检测单糖。然而，不依赖T1R的途径不能解释对二糖和低聚糖的反应，如蔗糖、麦芽糖和麦芽三糖，这些都不是谷氨酸或SGLT1的底物。利用RT-PCR、定量PCR、原位杂交和免疫组织化学等方法，我们发现味觉细胞表达多种α-糖苷酶(如淀粉酶和中性α-葡萄糖苷酶C)和所谓的肠道“刷状缘”二糖水解酶(如麦芽糖酶-糖淀粉酶和蔗糖酶-异麦芽糖苷酶)。用二糖酶抑制剂治疗舌头可以降低味觉神经对双糖的反应，但不会降低对单糖或非热量甜味剂的反应，这表明舌头的双糖酶是起作用的。这些味觉细胞表达的酶可能会将饮食中的双糖和淀粉水解物局部分解成单糖，作为T1R非依赖糖感觉通路的底物。
The primary sweet sensor in mammalian taste cells for sugars and noncaloric sweeteners is the heteromeric combination of type 1 taste receptors 2 and 3 (T1R2+ T1R3, encoded by Tas1r2 and Tas1r3 genes). However, in the absence of T1R2+ T1R3 (e. g., in Tas1r3 KO mice), animals still respond to sugars, arguing for the presence of T1R-independent detection mechanism(s). Our previous findings that several glucose transporters (GLUTs), sodium glucose cotransporter 1 (SGLT1), and the ATP-gated K+ (K-ATP) metabolic sensor are preferentially expressed in the same taste cells with T1R3 provides a potential explanation for the T1R-independent detection of sugars: sweet-responsive taste cells that respond to sugars and sweeteners may contain a T1R-dependent (T1R2+ T1R3) sweet-sensing pathway for detecting sugars and noncaloric sweeteners, as well as a T1R-independent (GLUTs, SGLT1, K-ATP) pathway for detecting monosaccharides. However, the T1R-independent pathway would not explain responses to disaccharide and oligomeric sugars, such as sucrose, maltose, and maltotriose, which are not substrates for GLUTs or SGLT1. Using RT-PCR, quantitative PCR, in situ hybridization, and immunohistochemistry, we found that taste cells express multiple alpha-glycosidases (e. g., amylase and neutral a glucosidase C) and so-called intestinal "brush border" disaccharide-hydrolyzing enzymes (e. g., maltase-glucoamylase and sucrase-isomaltase). Treating the tongue with inhibitors of disaccharidases specifically decreased gustatory nerve responses to disaccharides, but not to monosaccharides or noncaloric sweeteners, indicating that lingual disaccharidases are functional. These taste cell-expressed enzymes may locally break down dietary disaccharides and starch hydrolysis products into monosaccharides that could serve as substrates for the T1R-independent sugar sensing pathways.