Regulation of amino acid absorption in the mammalian small intestine

哺乳动物小肠氨基酸吸收的调节

• 批准号: 9174959
• 负责人: Uma Sundaram
• 金额: $ 47.81万
• 依托单位: MARSHALL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-01 至 2021-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9174959
• 关键词: Affect; Affinity; Amino Acids; Apoptosis; Architecture; Assimilations; Body Weight decreased; Cell Line; Cells; Chronic; Cyclic AMP-Dependent Protein Kinases; Data; Development; Diarrhea; Disease; Electrolytes; Enterocytes; Epithelial Cells; Epithelium; Fluids and Secretions; Foundations; Glutamine; Health; Homeostasis; Human; Immune; In Vitro; Inflammation Mediators; Inflammatory Bowel Diseases; Inflammatory disease of the intestine; Intestinal Diseases; Intestinal Mucosa; Intestines; Leukotrienes; Lipoxygenase; Liquid substance; Malabsorption Syndromes; Malnutrition; Mediating; Modeling; Molecular; Mucous Membrane; Nutrient; Nutritional Support; Oryctolagus cuniculus; Pathway interactions; Process; Prostaglandin-Endoperoxide Synthase; Prostaglandins; Protein Kinase C; Rattus; Regulation; Secondary to; Small Intestines; Source; Sum; Time; Villus; Wound Healing; absorption; base; brush border membrane; cell growth regulation; crypt cell; deprivation; design; enteritis; improved; intestinal epithelium; novel; symporter

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.

氨基酸谷氨酰胺是肠上皮细胞的主要营养物质