Angiotensin type 2 receptor in pancreatic islets of adult rats: a novel insulinotropic mediator

作者：Shao Chunhong; Zucker Irving H; Gao Lie^*

来源：American Journal of Physiology - Endocrinology And Metabolism, 2013, 305(10): E1281-E1291.

DOI：10.1152/ajpendo.00286.2013

• compound 21
• insulin production
• INS-1E cells

In the present study, we evaluated the relative abundance of angiotensin type 2 receptor (AT(2)R) protein in various tissues of adult rats. We found that pancreatic islets expressed the highest AT(2)R protein compared with all other tissues. Accordingly, we then determined the functional significance of AT(2)R in the endocrine pancreas in in vivo and in vitro experiments by using angiotensin II (ANG II) alone, losartan (Los; AT(1)R antagonist), compound 21 (C21; AT(2)R agonist), and PD-123319 (PD; AT(2)R antagonist). Experiments carried out in rats indicated that, 1) ANG II treatment significantly increased plasma insulin concentration (1.51 +/- 0.20 vs. 0.82 +/- 0.14 ng/ml, n = 7, P %26lt; 0.05) in the fed state. This insulinotropic effect was further augmented by combined treatment with ANG II + Los (2.31 +/- 0.25 ng/ml, n = 7, P %26lt; 0.01). C21 also elevated insulin levels (2.13 +/- 0.20 ng/ml, n = 7, P %26lt; 0.01), which was completely abolished by PD. 2) ANG II impaired glucose tolerance, whereas ANG II + Los or C21 improved this function. 3) All treated rats displayed an enhanced insulin secretory response to a glucose challenge. 4) All treated rats displayed upregulated proinsulin 2 mRNA and insulin protein expression in the pancreas. In in vitro experiments using INS-1E cells and isolated rat islets, we found that AT(2)R activation significantly improved insulin biosynthesis and secretion. These results suggest that the AT(2)R functions as an insulinotropic mediator. AT(2)R and its downstream signaling pathways may be potential therapeutic targets for diabetes.

• 出版日期2013-11