Epithelial Function and Development Group, Department of Cellular and Molecular Physiology, Institute of Translational Medicine, Faculty of Health and Life Sciences, University of Liverpool, Liverpool L69 7ZJ, UK.
Proc Nutr Soc. 2011 May;70(2):185-93. doi: 10.1017/S0029665111000103. Epub 2011 Mar 30.
Epithelial cells lining the inner surface of the intestinal epithelium are in direct contact with a lumenal environment that varies dramatically with diet. It has long been suggested that the intestinal epithelium can sense the nutrient composition of lumenal contents. It is only recently that the nature of intestinal nutrient-sensing molecules and underlying mechanisms have been elucidated. There are a number of nutrient sensors expressed on the luminal membrane of endocrine cells that are activated by various dietary nutrients. We showed that the intestinal glucose sensor, T1R2+T1R3 and the G-protein, gustducin are expressed in endocrine cells. Eliminating sweet transduction in mice in vivo by deletion of either gustducin or T1R3 prevented dietary monosaccharide- and artificial sweetener-induced up-regulation of the Na+/glucose cotransporter, SGLT1 observed in wild-type mice. Transgenic mice, lacking gustducin or T1R3 had deficiencies in secretion of glucagon-like peptide 1 (GLP-1) and, glucose-dependent insulinotrophic peptide (GIP). Furthermore, they had an abnormal insulin profile and prolonged elevation of postprandial blood glucose in response to orally ingested carbohydrates. GIP and GLP-1 increase insulin secretion, while glucagon-like peptide 2 (GLP-2) modulates intestinal growth, blood flow and expression of SGLT1. The receptor for GLP-2 resides in enteric neurons and not in any surface epithelial cells, suggesting the involvement of the enteric nervous system in SGLT1 up-regulation. The accessibility of the glucose sensor and the important role that it plays in regulation of intestinal glucose absorption and glucose homeostasis makes it an attractive nutritional and therapeutic target for manipulation.
肠上皮内表面的上皮细胞与腔环境直接接触，而腔环境的组成随饮食变化很大。长期以来，人们一直认为肠上皮可以感知腔内容物的营养成分。直到最近，肠营养感应分子的性质和潜在机制才被阐明。在肠内分泌细胞的腔膜上表达了许多营养传感器，它们可以被各种膳食营养素激活。我们发现，肠道葡萄糖传感器 T1R2+T1R3 和 G 蛋白 gustducin 在内分泌细胞中表达。在体内通过 gustducin 或 T1R3 的缺失消除小鼠的甜味转导，可防止野生型小鼠中观察到的膳食单糖和人工甜味剂诱导的 Na+/葡萄糖共转运蛋白 SGLT1 的上调。缺乏 gustducin 或 T1R3 的转基因小鼠表现出胰高血糖素样肽 1 (GLP-1) 和葡萄糖依赖性胰岛素释放肽 (GIP) 分泌不足。此外，它们对口服摄入的碳水化合物的胰岛素反应异常，餐后血糖升高时间延长。GIP 和 GLP-1 增加胰岛素分泌，而胰高血糖素样肽 2 (GLP-2) 调节肠生长、血流和 SGLT1 的表达。GLP-2 的受体位于肠神经元中，而不在任何表面上皮细胞中，这表明肠神经系统参与了 SGLT1 的上调。葡萄糖传感器的可及性及其在调节肠道葡萄糖吸收和葡萄糖稳态方面的重要作用，使其成为营养和治疗干预的有吸引力的目标。
