Malinauskas M, Wallenius V, Fändriks L, Casselbrant A
Institute of Physiology and Pharmacology, Medical Academy, Lithuanian University of Health Sciences, Kaunas, Lithuania Department of Gastrosurgical Research and Education, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Sweden.
Department of Gastrosurgical Research and Education, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Sweden.
J Renin Angiotensin Aldosterone Syst. 2015 Dec;16(4):1101-8. doi: 10.1177/1470320315599514. Epub 2015 Aug 26.
Recently it was shown that the classic renin-angiotensin system (RAS) is locally expressed in small intestinal enterocytes and exerts autocrine control of glucose transport. The aim of this study was to investigate if key components for the Angiotensin III (AngIII) and IV (AngIV) formation enzymes and the AngIV receptor, insulin-regulated aminopeptidase (IRAP), are present in the healthy jejunal mucosa. A second aim was to investigate AngIV effects on glucose-induced mucosal transport in vitro.
Enteroscopy with mucosal biopsy sampling was performed in healthy volunteers. ELISA, Western blotting and immunohistochemistry were used to assess the protein levels and localization. The functional effect of AngIV was examined in Ussing chambers.
The substrate Angiotensin II, the enzymes aminopeptidases-A, B, M as well as IRAP were detected in the jejunal mucosa. Immunohistochemistry localized the enzymes to the apical brush-border membrane whereas IRAP was localized in the subapical cytosolic compartment in the enterocyte. AngIV increased the glucose-induced electrogenic transport in vitro.
The present study indicates the presence of substrates and enzymes necessary for AngIV formation as well as the receptor IRAP in the jejunal mucosa. The functional data suggest that AngIV regulates glucose uptake in the healthy human small intestine.
最近有研究表明，经典肾素-血管紧张素系统（RAS）在小肠肠上皮细胞中局部表达，并对葡萄糖转运发挥自分泌控制作用。本研究的目的是调查健康空肠黏膜中是否存在血管紧张素III（AngIII）和IV（AngIV）形成酶以及AngIV受体（胰岛素调节氨肽酶，IRAP）的关键成分。第二个目的是研究AngIV对体外葡萄糖诱导的黏膜转运的影响。
对健康志愿者进行肠镜检查并采集黏膜活检样本。采用酶联免疫吸附测定（ELISA）、蛋白质印迹法和免疫组织化学法评估蛋白质水平和定位。在尤斯灌流小室中检测AngIV的功能作用。
在空肠黏膜中检测到底物血管紧张素II、氨肽酶A、B、M以及IRAP。免疫组织化学将这些酶定位到顶端刷状缘膜，而IRAP定位于肠上皮细胞顶端下的胞质区室。AngIV增加了体外葡萄糖诱导的电转运。
本研究表明空肠黏膜中存在AngIV形成所需的底物和酶以及受体IRAP。功能数据表明AngIV调节健康人小肠中的葡萄糖摄取。
