Enalapril Diminishes the Diabetes-Induced Changes in Intestinal Morphology,Intestinal RAS and Blood SCFA Concentration in Rats |
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| Authors: | Kinga Jaworska,Wojciech Kopacz,Mateusz Koper,Mateusz Szudzik,Marta Gawryś -Kopczyń ska,Marek Konop,Tomasz Hutsch,Dawid Chabowski,Marcin Ufnal |
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| Affiliation: | Laboratory of Centre for Preclinical Research, Department of Experimental Physiology and Pathophysiology, Medical University of Warsaw, Pawinskiego 3c Street, 02-106 Warsaw, Poland; (W.K.); (M.K.); (M.S.); (M.G.-K.); (M.K.); (T.H.); (D.C.); (M.U.) |
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| Abstract: | Evidence suggests that microbiota-derived metabolites, including short-chain fatty acids (SCFAs) and trimethylamine-oxide (TMAO), affect the course of diabetic multiorgan pathology. We hypothesized that diabetes activates the intestinal renin–angiotensin system (RAS), contributing to gut pathology. Twelve-week-old male rats were divided into three groups: controls, diabetic (streptozotocin-induced) and diabetic treated with enalapril. Histological examination and RT-qPCR were performed to evaluate morphology and RAS expression in the jejunum and the colon. SCFA and TMAO concentrations in stools, portal and systemic blood were evaluated. In comparison to the controls, the diabetic rats showed hyperplastic changes in jejunal and colonic mucosa, increased plasma SCFA, and slightly increased plasma TMAO. The size of the changes was smaller in enalapril-treated rats. Diabetic rats had a lower expression of Mas receptor (MasR) and angiotensinogen in the jejunum whereas, in the colon, the expression of MasR and renin was greater in diabetic rats. Enalapril-treated rats had a lower expression of MasR in the colon. The expression of AT1a, AT1b, and AT2 receptors was similar between groups. In conclusion, diabetes produces morphological changes in the intestines, increases plasma SCFA, and alters the expression of renin and MasR. These alterations were reduced in enalapril-treated rats. Future studies need to evaluate the clinical significance of intestinal pathology in diabetes. |
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| Keywords: | intestinal RAS diabetes ACE-I SCFA TMAO |
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