Glucose promotes its own metabolism by acting on the cell-surface glucose-sensing receptor T1R3
Glucose promotes its own metabolism by acting on the cell-surface glucose-sensing receptor T1R3
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DOI：
10.1507/endocrj.ej13-0431
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发表时间：
2014-02-01
影响因子：
2
通讯作者：
Kojima, Itaru
中科院分区：
文献类型：
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作者：
Nakagawa, Yuko;Ohtsu, Yoshiaki;Kojima, Itaru
味觉1型受体3 （T1R3）的同二聚体在胰腺β细胞中作为甜味感知受体起作用。这种受体被各种甜分子激活，包括糖，如葡萄糖。为了确定该受体在葡萄糖诱导的胰岛素分泌中的作用，我们研究了该受体是否调节MIN6细胞的葡萄糖代谢。我们测量了表达荧光素酶的MIN6细胞中细胞内ATP （[ATP](i)）的变化。三氯蔗糖是T1R3的一种激动剂，在存在5.5 mM葡萄糖的情况下诱导[ATP](i)立即和持续升高。三氯蔗糖的作用是剂量依赖性的，在5 mM时，效果大于25 mM葡萄糖诱导的效果。与此相反，碳二醇、GLP-1或高浓度钾均不能重现三氯蔗糖的作用。三氯蔗糖促进了线粒体燃料甲基琥珀酸诱导的[ATP](i)的增加，并增强了葡萄糖诱导的[ATP](i)的升高。非代谢葡萄糖类似物3- o -甲基葡萄糖作为T1R3的激动剂，可诱导[ATP]的小而短暂的增加(i)。3- o -甲基葡萄糖增强了甲基琥珀酸诱导的[ATP]升高(i)，也增强了葡萄糖诱导的[ATP]升高(i)。使用shRNA敲低T1R3可减弱[ATP](i)-对高浓度葡萄糖的反应，也可减少葡萄糖诱导的胰岛素分泌。这些结果表明，激活T1R3的同型二聚体促进了线粒体的代谢途径并增加了ATP的产生。使用3- o -甲基葡萄糖获得的结果表明，葡萄糖通过作用于T1R3的同型二聚体，促进其自身的代谢。
A homodimer of taste type 1 receptor 3 (T1R3) functions as a sweet taste-sensing receptor in pancreatic beta-cells. This receptor is activated by various sweet molecules including sugars such as glucose. To determine the role of this receptor in glucose-induced insulin secretion, we addressed whether or not this receptor modulates glucose metabolism in MIN6 cells. We measured changes in intracellular ATP ([ATP](i)) in MIN6 cells expressing luciferase. Sucralose, an agonist of T1R3, induced immediate and sustained elevation of [ATP](i) in the presence of 5.5 mM glucose. The effect of sucralose was dose-dependent and, at 5 mM, was greater than that induced by 25 mM glucose. In contrast, carbachol, GLP-1 or high concentration of potassium did not reproduce the sucralose action. Sucralose facilitated the increase in [ATP](i) induced by a mitochondrial fuel methylsuccinate, and potentiated glucose-induced elevation of [ATP](i). Administration of a non-metabolizable glucose analogue, 3-O-methylglucose, which acts as an agonist of T1R3, induced a small and transient increase in [ATP](i). 3-O-Methylglucose augmented elevation of [ATP](i) induced by methylsuccinate, and also enhanced glucose-induced increase in [ATP](i). Knock down of T1R3 by using shRNA attenuated [ATP](i)-response to high concentration of glucose and also reduced the glucose-induced insulin secretion. These results indicate that activation of the homodimer of T1R3 facilitates the metabolic pathway in mitochondria and augments ATP production. The results obtained by using 3-O-methylglucose suggest that glucose, by acting on the homodimer of T1R3, promotes its own metabolism.