Local expression of AP/AngIV/IRAP and effect of AngIV on glucose-induced epithelial transport in human jejunal mucosa

BACKGROUND: 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. MATERIAL AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.