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Aldosterone induced up-expression of ICAM-1 and ET-1 in pancreatic islet endothelium may associate with progression of T2D

Wang, Jinbang, Hu, Huiqing, Song, Jia, Yan, Fei, Qin, Jun, Guo, Xinghong, Cui, Chen, He, Qin, Hou, Xinguo, Liu, Fuqiang, Chen, Li
Biochemical and biophysical research communications 2019 v.512 no.4 pp. 750-757
aldosterone, animal disease models, blood serum, cell adhesion, endothelins, endothelium, fibrosis, glucose, histology, inflammation, intercellular adhesion molecule-1, islets of Langerhans, macrophages, messenger RNA, metabolism, mice, mineralocorticoid receptors, noninsulin-dependent diabetes mellitus, patients, protein content, risk factors
Previous studies have demonstrated that excess aldosterone impairs glucose metabolism. However, the underlying mechanism is still misty. Aldosterone has been proved a risk factor of fibrosis and inflammation. And the histology of islets from patients with type 2 diabetes (T2D) also displays inflammation and fibrosis. But it is unclear whether aldosterone has direct impact on islet inflammation and fibrosis in T2D. Islet endothelium plays a significant role in the maintenance of islet beta cell function and has a close relationship with islet fibrosis and inflammation. Therefore, we focused on the effect of aldosterone on the islet endothelium. In this study, we utilized a diabetic db/db mouse model and examined serum aldosterone levels, islet macrophages infiltration, and islet fibrosis. After we confirmed that there was an increased expression of intercellular cell adhesion molecule-1 (ICAM-1) and endothelin-1 (ET-1) in islet of diabetic mice compared with wild type mice. We next determined that aldosterone increased expression of ICAM-1 and ET-1 in both mRNA and protein levels in islet endothelium in vitro. And then we tested the expression of mineralocorticoid receptor (MR) in islet endothelium in vitro and in vivo. Our results showed that aldosterone can up-regulate the expression levels of ICAM-1 and ET-1 through MR. These findings suggest excess aldosterone might participate in islet inflammation and fibrosis in T2D.