GLUT2 accumulation in enterocyte apical and intracellular membranes: a study in morbidly obese human subjects and ob/ob and high fat-fed mice.
GLUT2 accumulation in enterocyte apical and intracellular membranes: a study in morbidly obese human subjects and ob/ob and high fat-fed mice.
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DOI：
10.2337/db10-1740
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发表时间：
2011-10
期刊：
影响因子：
7.7
通讯作者：
Brot-Laroche E
中科院分区：
文献类型：
--
作者：
Ait-Omar A;Monteiro-Sepulveda M;Poitou C;Le Gall M;Cotillard A;Gilet J;Garbin K;Houllier A;Château D;Lacombe A;Veyrie N;Hugol D;Tordjman J;Magnan C;Serradas P;Clément K;Leturque A;Brot-Laroche E
在健康的啮齿动物中，对高糖饮食和胰岛素的肠道糖吸收是由肠细胞质膜上的GLUT2调节的。失去胰岛素的作用维持顶端的GLUT2位置。在人类肠上皮细胞中，顶端GLUT2的位置尚未被报道，但可能在胰岛素抵抗的条件下被揭示。对62例表型良好的病态肥胖者和7例瘦肉者进行了GLUT2在空肠上皮细胞的亚细胞定位。在口服二甲双胍的ob/ob和ob/+小鼠或高脂低碳水化合物饮食喂养的C57BL/6小鼠中检测GLUT2定位。通过口服葡萄糖耐量试验和腔内分泌[U-14C]-3-O-甲基葡萄糖来评价葡萄糖的吸收和分泌。在人的肠上皮细胞中，GLUT2持续定位于基底膜。顶端GLUT2位置在瘦的受试者中缺失，但在76%的肥胖者中观察到，并且与胰岛素抵抗和血糖有关。此外，在接受低碳水化合物/高脂肪饮食的39%肥胖者中，早期内体抗原1(EEA1)在细胞内的GLUT2积累与MGAT4a活性(糖基化)降低有关。低碳水化合物/高脂肪饮食12个月的小鼠也表现出内体GLUT2积聚和葡萄糖吸收减少。在ob/ob小鼠中，二甲双胍促进顶端GLUT2并改善血糖稳态。空腹高血糖ob/ob小鼠的顶端GLUT2将葡萄糖释放到肠腔中的量增加了两倍。在病态肥胖的胰岛素抵抗受试者中，GLUT2积聚在肠细胞的顶膜和/或内膜上。在功能上，心尖部GLUT2有利于减少葡萄糖跨上皮交换。因此，肠道细胞中GLUT2位置的改变是肠道适应人类代谢病理的标志。
In healthy rodents, intestinal sugar absorption in response to sugar-rich meals and insulin is regulated by GLUT2 in enterocyte plasma membranes. Loss of insulin action maintains apical GLUT2 location. In human enterocytes, apical GLUT2 location has not been reported but may be revealed under conditions of insulin resistance. Subcellular location of GLUT2 in jejunal enterocytes was analyzed by confocal and electron microscopy imaging and Western blot in 62 well-phenotyped morbidly obese subjects and 7 lean human subjects. GLUT2 locations were assayed in ob/ob and ob/+ mice receiving oral metformin or in high-fat low-carbohydrate diet–fed C57Bl/6 mice. Glucose absorption and secretion were respectively estimated by oral glucose tolerance test and secretion of [U-14C]-3-O-methyl glucose into lumen. In human enterocytes, GLUT2 was consistently located in basolateral membranes. Apical GLUT2 location was absent in lean subjects but was observed in 76% of obese subjects and correlated with insulin resistance and glycemia. In addition, intracellular accumulation of GLUT2 with early endosome antigen 1 (EEA1) was associated with reduced MGAT4a activity (glycosylation) in 39% of obese subjects on a low-carbohydrate/high-fat diet. Mice on a low-carbohydrate/high-fat diet for 12 months also exhibited endosomal GLUT2 accumulation and reduced glucose absorption. In ob/ob mice, metformin promoted apical GLUT2 and improved glucose homeostasis. Apical GLUT2 in fasting hyperglycemic ob/ob mice tripled glucose release into intestinal lumen. In morbidly obese insulin-resistant subjects, GLUT2 was accumulated in apical and/or endosomal membranes of enterocytes. Functionally, apical GLUT2 favored and endosomal GLUT2 reduced glucose transepithelial exchanges. Thus, altered GLUT2 locations in enterocytes are a sign of intestinal adaptations to human metabolic pathology.
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影响因子：
15.9
作者：
Kahn, BB;Flier, JS
通讯作者：
Flier, JS
影响因子：
5.8
作者：
Ikeda, T;Iwata, K;Murakami, H
通讯作者：
Murakami, H
影响因子：
7.7
作者：
Kellett, GL;Brot-Laroche, E
通讯作者：
Brot-Laroche, E
DOI：
10.1152/ajpendo.00332.2001
发表时间：
2002-04-01
影响因子：
5.1
作者：
Burcelin, M;Crivelli, V;Thorens, B
通讯作者：
Thorens, B
影响因子：
5.5
作者：
Habold, C;Foltzer-Jourdainne, C;Oudart, H
通讯作者：
Oudart, H