Regulation of amino acid absorption in the mammalian small intestine

氨基酸谷氨酰胺是肠道细胞的主要营养物质。 因此，对上皮的健康至关重要。然而，谷氨酰胺是如何被同化的 在正常哺乳动物的小肠和/或主要的粘膜疾病中，如 炎症性肠病(IBD)还不是很清楚。谷氨酰胺通过钠离子吸收。 谷氨酰胺共转运(NGCT)在肠细胞刷状缘膜(BBM)上。 我们已经证明B0AT1介导了绒毛细胞BBM上的NGCT。在.中 范式转换，我们展示了BBM上唯一的营养吸收过程 隐窝细胞，特别是SN2，在这些细胞中介导NGCT。此外，在一只兔子身上 类似IBD的慢性肠炎模型我们证明NGCT在 总额减少了。这种净抑制是绒毛细胞中B0AT1抑制和 SN2刺激隐窝细胞。B0AT1的抑制机制是次要的。 减少绒毛细胞BBM中共转运体的数量，而其机制是 在隐窝细胞中SN2的刺激是次要的，因为它增加了对 谷氨酰胺。因此，通过不同的转运蛋白在绒毛中发生的谷氨酰胺同化 而隐窝细胞在慢性炎症的肠道中受到独特的调节。重要的是 在人的IBD肠道中也看到了类似的结果。其他初步研究 表明已知的免疫炎症介质在慢性炎症中产生 肠道发炎可能是谷氨酰胺这些独特变化的原因 吸收。鉴于这一背景，总体目标是确定免疫 慢性阻塞性肺疾病绒毛B0AT1和隐窝细胞SN2的调控机制 肠子发炎。更好地了解人体谷氨酰胺吸收的调节 正常和IBD肠道将为开发更有效、更特异的肠道提供基础 基于免疫的营养疗法治疗IBD。

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.