Regulation of amino acid absorption in the mammalian small intestine

氨基酸谷氨酰胺是肠上皮细胞的主要营养素 因此对上皮的健康至关重要。然而，谷氨酰胺是如何被吸收的， 在正常哺乳动物小肠和/或在主要粘膜疾病中， 炎症性肠病（IBD）不是众所周知的。谷氨酰胺通过Na- 肠上皮细胞刷状缘膜（BBM）上的谷氨酰胺共转运（NGcT）。 我们已经证明B 0AT 1介导绒毛细胞BBM上的NGcT。和 范式转变，我们证明了BBM上唯一的营养吸收过程， 在这些细胞中，SN 2介导NGcT。此外，在一只兔子 在类似IBD的慢性肠道炎症模型中，我们证明了NGcT在 总数减少了。该净抑制是绒毛细胞中的B 0AT 1抑制和 在隐窝细胞中的SN 2刺激。B 0AT 1的抑制机制是次要的。 绒毛细胞BBM中共转运蛋白的数量减少，而 刺激SN 2在隐窝细胞中是继发于对SN 2的亲和力的增加。 谷氨酰胺。因此，通过绒毛中不同的转运蛋白发生的谷氨酰胺同化作用 并且在慢性发炎的肠中，隐窝细胞受到独特的调节。重要的是， 在人IBD肠中观察到类似的结果。其他初步研究 表明，免疫炎症介质已知产生于慢性 肠道发炎可能是谷氨酰胺这些独特变化的原因 吸收在此背景下，总体目标是确定免疫 慢性前列腺炎绒毛B 0AT 1和隐窝细胞SN 2的调节机制 肠道发炎更好地了解谷氨酰胺吸收的调节， 正常和IBD肠道将为开发更有效，特异性 基于免疫的IBD营养疗法。

The amino acid glutamine is the primary nutrient for the intestinal enterocytes and thus, critical for the health of the epithelium. However, how glutamine is assimilated in the normal mammalian small intestine and/or in a primarily mucosal disease such as inflammatory bowel disease (IBD) is not well known. Glutamine is absorbed via Na- glutamine co-transport (NGcT) on the brush border membrane (BBM) of enterocytes. We have demonstrated that B0AT1 mediates NGcT on the BBM of villus cells. And in paradigm shift, we demonstrated the only nutrient absorptive process on the BBM of crypt cells, specifically SN2, which mediates NGcT in these cells. Further, in a rabbit model of chronic intestinal inflammation resembling IBD we demonstrated that NGcT in total was reduced. This net inhibition was a sum of B0AT1 inhibition in villus cells and SN2 stimulation in crypt cells. The mechanism of inhibition of B0AT1 was secondary to a reduction in the number of co-transporters in the villus cell BBM while the mechanism of stimulation of SN2 in crypt cells was secondary to an increase in the affinity for glutamine. Thus, glutamine assimilation which occurs via distinct transporters in villus and crypt cells is uniquely regulated in the chronically inflamed intestine. Importantly, similar results were seen in the human IBD intestine. Additional preliminary studies indicated that immune inflammatory mediators known to be produced in the chronically inflamed intestine may be responsible for these unique alterations in glutamine absorption. Given this background, the overall aim is to determine the immune mechanism of regulation of B0AT1 in villus and SN2 in crypt cells in the chronically inflamed intestine. Better understanding of the regulation of glutamine absorption in the normal and IBD intestine will provide the foundation to develop more efficacious, specific immune based nutritional therapies for IBD.