葡萄糖跨肠刷状缘膜转运在代谢调节中起关键作用。取决于腔内葡萄糖浓度,葡萄糖主要通过钠依赖性葡萄糖转运蛋白(SGLT1)和促进转运蛋白葡萄糖转运蛋白(GLUT2)转运。SGLT1是根尖膜组成型,在低腔葡萄糖浓度下具有活性,当浓度高于50mM时,葡萄糖主要由GLUT2(从基底外侧膜募集)转运。饮食酚类化合物可以通过抑制SGLT1和GLUT2来降低餐后葡萄糖反应来调节葡萄糖稳态。
已经使用大鼠的刷状边界膜囊泡检查了肠道葡萄糖转运的酚类抑制作用,猪或兔子,非洲爪猿卵母细胞和最近的Caco-2细胞,这是最有希望的协调体外实验。
超过100μM的酚类浓度已被证明能成功抑制葡萄糖转运。一般来说,糖苷配基槲皮素,杨梅素,据报道,非塞素或芹菜素强烈抑制GLUT2,而槲皮素-3-O-糖苷已被证明在SGLT1中更有效。此外,观察到表没食子儿茶素以及表儿茶素和表没食子儿茶素没食子酸酯对SGLT1和GLUT2均有抑制作用。
虽然,关于酚类葡萄糖转运抑制的有价值的信息是已知的,然而,关于黄酮类糖苷和糖苷配基发挥显着抑制作用存在一些分歧,以及酚酸的抑制作用仍不清楚。这篇评论旨在收集,比较和讨论有关酚类抑制葡萄糖转运蛋白的现有信息和争议。还包括有关酚类-葡萄糖转运蛋白相互作用的物理化学机制的详细讨论。
Glucose transport across the intestinal brush border membrane plays a key role in metabolic regulation. Depending on the luminal glucose concentration, glucose is mainly transported by the sodium- dependent glucose transporter (SGLT1) and the facilitated-transporter glucose transporter (GLUT2). SGLT1 is apical membrane-constitutive and it is active at a low luminal glucose concentration, while at concentrations higher than 50 mM, glucose is mainly transported by GLUT2 (recruited from the basolateral membrane). Dietary phenolic compounds can modulate glucose homeostasis by decreasing the postprandial glucose response through the inhibition of SGLT1 and GLUT2.
Phenolic inhibition of intestinal glucose transport has been examined using brush border membrane vesicles from rats, pigs or rabbits, Xenopus oocytes and more recently Caco-2 cells, which are the most promising for harmonizing in vitro experiments.
Phenolic concentrations above 100 µM has been proved to successfully inhibit the glucose transport. Generally, the aglycones quercetin, myricetin, fisetin or apigenin have been reported to strongly inhibit GLUT2, while quercetin-3-O-glycoside has been demonstrated to be more effective in SGLT1. Additionally, epigallocatechin as well as epicatechin and epigallocatechin gallates were observed to be inhibited on both SGLT1 and GLUT2.
Although, valuable information regarding the phenolic glucose transport inhibition is known, however, there are some disagreements about which flavonoid glycosides and aglycones exert significant inhibition, and also the inhibition of phenolic acids remains unclear. This
review aims to collect, compare and discuss the available information and controversies about the phenolic inhibition of glucose transporters. A detailed discussion on the physicochemical mechanisms involved in phenolics-glucose transporters interactions is also included.