The bradykinin BK2 receptor mediates angiotensin II receptor type 2 stimulated rat duodenal mucosal alkaline secretion

BACKGROUND: This study investigates bradykinin and nitric oxide as potential mediators of AT2-receptor-stimulated duodenal mucosal alkaline secretion. Duodenal mucosal alkaline secretion was measured in methohexital- and α-chloralose-anaesthetised rats by means of in situ pH-stat titration. Immunohistochemistry and Western blot were used to identify the BK2 receptors. RESULTS: The AT2 receptor agonist CGP42112A (0.1 μg kg(-1 )min(-1)) administered intravenously increased the duodenal mucosal alkaline secretion by ~50 %. This increase was sensitive to the selective BK2 receptor blocker HOE140 (100 ng/kg iv), but not to luminal administration of the NOS blocker L-NAME (0.3 mM). Mean arterial pressure did not differ between groups during the procedures. Immunohistochemistry showed a distinct staining of the crypt epithelium and a moderate staining of basal cytoplasm in villus enterocytes. CONCLUSION: The results suggest that the AT2-receptor-stimulated alkaline secretion is mediated via BK2 receptors located in the duodenal cryptal mucosal epithelium

Higher circulating bile acid concentrations in obese patients with type 2 diabetes

Background Bile acids (BAs) play an important role in releasing incretin hormones via the enteroendocrine L-cell surface TGR5 receptors. The aim of this study was to investigate the difference in BA concentration at baseline and in response to a meal stimulus between type 2 diabetes mellitus (T2DM) and a matched normoglycaemic group. Materials and methods A cross-sectional study of 12 patients with known T2DM and 12 matched normoglycaemic controls compared BA fractions after an overnight fast and following a standard meal. Results The T2DM group had higher baseline glucose (P &lt; 0.001), but baseline total BA, total glycine conjugated BAs (GCBA) and total taurine conjugated BA (TCBA) were similar between both groups. The T2DM group compared to the normoglycaemic group had a higher post-prandial peak change in total BAs 4.28 (3.51–5.38) µmol/L vs. 0.88 (0.60–1.57) µmol/L ( P &lt; 0.001) and peak total GCBA 2.77 (1.07–4.19) µmol/L vs. 0.94 (0.34–1.15) µmol/L ( P &lt; 0.0001), but similar peak total TCBA 0.36 (0.02–0.76) µmol/L vs. 0.08 (0.04–0.22) µmol/L ( P=0.91). Conclusion The post-prandial bile acid response is elevated in obese patients with T2DM compared to matched normoglycaemic individuals. </jats:sec