Ramipril treatment suppresses islet fibrosis in Otsuka Long–Evans Tokushima fatty rats

Abstract

We evaluated whether ramipril, one of long-acting ACEIs, has a direct effect on pancreas islets in animal model of type 2 diabetes. OLETF rats were treated with ramipril for 24 weeks. We assessed the body weight, glucose tolerance, and the amount of islet fibrosis. RT-PCR and Western blot analysis of transforming growth factor-β with its downstream signals were performed from the pancreas. Ramipril treatment remarkably reduced weight gain and the area under the curve of glucose. Islet fibrosis and the expression of TGF-β with its downstream signal molecules were significantly reduced in the pancreas of ramipril-treated group than in control and paired-feeding group. These beneficial effects of ramipril might be related to the downregulation of TGF-β and its downstream signals in OLETF rats. To our knowledge, this is the first report suggesting the potential effect of ramipril on the prevention of islet destruction by fibrosis in the animal model of type 2 diabetes mellitus.

Keywords Ramipril; Otsuka Long–Evans Tokushima fatty rat; Islet fibrosis; Transforming growth factor-β; α-Smooth muscle actin