Flavonoid inhibition of sodium-dependent vitamin C transporter 1 (SVCT1) and glucose transporter isoform 2 (GLUT2), intestinal transporters for vitamin C and glucose
Flavonoid inhibition of sodium-dependent vitamin C transporter 1 (SVCT1) and glucose transporter isoform 2 (GLUT2), intestinal transporters for vitamin C and glucose
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DOI：
10.1074/jbc.m110496200
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发表时间：
2002-05-03
影响因子：
4.8
通讯作者：
Levine, M
中科院分区：
文献类型：
--
作者：
Song, J;Kwon, O;Levine, M
维生素C和黄酮类化合物，多酚类化合物具有不确定的功能，丰富的水果和蔬菜。我们推测，黄酮类化合物具有延迟或抑制维生素C和葡萄糖吸收的新的调节作用，这两种物质在结构上相似。从六种黄酮类化合物中，至少选择了12种化合物进行研究。我们通过在中国仓鼠卵巢细胞中转染和过表达SVCT 1（h），研究了所选黄酮类化合物对肠道维生素C转运蛋白SVCT 1（h）的影响。黄酮类化合物可逆地抑制转染细胞中的维生素C转运，IC 50值为10-50 μ M，预期浓度具有生理学后果。最有效的抑制剂是黄酮醇类，其中槲皮素在食物中最丰富。由于中国仓鼠卵巢细胞具有内源性维生素C转运功能，我们在非洲爪蟾卵母细胞中表达SVCT 1（h），以研究转运抑制机制。槲皮素是抗坏血酸转运的可逆和非竞争性抑制剂; Ki 17.8 μ M。槲皮素是非洲爪蟾卵母细胞中表达的GLUT 2的有效非竞争性抑制剂; Ki 22.8 μ M。当糖尿病大鼠给予葡萄糖和槲皮素时，与单独给予葡萄糖相比，高血糖显著降低。槲皮素也显着降低抗坏血酸吸收正常大鼠给予抗坏血酸加槲皮素相比，大鼠单独给予抗坏血酸。槲皮素是一种特异性的转运抑制剂，因为它不抑制肠糖转运蛋白GLUT 5和SGLT 1，注射和表达在爪蟾卵母细胞。槲皮素抑制SVCT 1（h），但不转运。综合考虑，这些数据表明，类黄酮调节维生素C和葡萄糖转运各自的肠道转运蛋白，并提出了一个新的功能类黄酮。
Vitamin C and flavonoids, polyphenols with uncertain function, are abundant in fruits and vegetables. We postulated that flavonoids have a novel regulatory action of delaying or inhibiting absorption of vitamin C and glucose, which are structurally similar. From six structural classes of flavonoids, at least 12 compounds were chosen for studies. We investigated the effects of selected flavonoids on the intestinal vitamin C transporter SVCT1(h) by transfecting and overexpressing SVCT1(h) in Chinese hamster ovary cells. Flavonoids reversibly inhibited vitamin C transport in transfected cells with IC50 values of 10-50 muM, concentrations expected to have physiologic consequences. The most potent inhibitor class was flavonols, of which quercetin is most abundant in foods. Because Chinese hamster ovary cells have endogenous vitamin C transport, we expressed SVCT1(h) in Xenopus laevis oocytes to study the mechanism of transport inhibition. Quercetin was a reversible and non-competitive inhibitor of ascorbate transport; K-i 17.8 muM. Quercetin was a potent non-competitive inhibitor of GLUT2 expressed in Xenopus oocytes; K-i 22.8 muM. When diabetic rats were administered glucose with quercetin, hyperglycemia was significantly decreased compared with administration of glucose alone. Quercetin also significantly decreased ascorbate absorption in normal rats given ascorbate plus quercetin compared with rats given ascorbate alone. Quercetin was a specific transport inhibitor, because it did not inhibit intestinal sugar transporters GLUT5 and SGLT1 that were injected and expressed in Xenopus oocytes. Quercetin inhibited but was not transported by SVCT1(h). Considered together, these data show that flavonoids modulate vitamin C and glucose transport by their respective intestinal transporters and suggest a new function for flavonoids.