Aldosterone induced up-expression of ICAM-1 and ET-1 in pancreatic islet endothelium may associate with progression of T2D
Aldosterone induced up-expression of ICAM-1 and ET-1 in pancreatic islet endothelium may associate with progression of T2D
复制标题
醛固酮诱导胰岛内皮细胞 ICAM-1 和 ET-1 表达上调可能与 T2D 进展相关
DOI：
10.1016/j.bbrc.2019.03.149
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发表时间：
2019
影响因子：
3.1
通讯作者：
Chen Li
中科院分区：
文献类型：
--
作者：
Wang Jinbang;Hu Huiqing;Song Jia;Yan Fei;Qin Jun;Guo Xinghong;Cui Chen;He Qin;Hou Xinguo;Liu Fuqiang;Chen Li
以往的研究表明，过量的醛固酮损害葡萄糖代谢。然而，其内在机制仍然是模糊的。醛固酮已被证实是纤维化和炎症的危险因素。2型糖尿病（T2D）患者胰岛的组织学也显示炎症和纤维化。但尚不清楚醛固酮是否对T2D的胰岛炎症和纤维化有直接影响。胰岛内皮细胞在维持胰岛β细胞功能中起着重要作用，与胰岛纤维化和炎症有着密切的关系。因此，我们重点研究了醛固酮对胰岛内皮细胞的影响。在这项研究中，我们利用糖尿病db/db小鼠模型，并检查血清醛固酮水平，胰岛巨噬细胞浸润和胰岛纤维化。我们证实糖尿病小鼠胰岛细胞间粘附分子-1（ICAM-1）和内皮素-1（ET-1）的表达较野生型小鼠增加。我们接下来确定醛固酮在体外增加胰岛内皮细胞ICAM-1和ET-1在mRNA和蛋白水平的表达。然后在体内外检测胰岛内皮细胞盐皮质激素受体（MR）的表达。本研究结果表明，醛固酮可通过MR上调ICAM-1和ET-1的表达水平，这些结果表明过量的醛固酮可能参与了T2D胰岛炎症和纤维化。
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 invitro. And then we tested the expression of mineralocorticoid receptor (MR) in islet endothelium invitroand invivo. 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.