{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T12:57:08Z","timestamp":1776257828988,"version":"3.50.1"},"reference-count":43,"publisher":"American Physiological Society","issue":"10","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Endocrinology and Metabolism"],"published-print":{"date-parts":[[2013,11,15]]},"abstract":"<jats:p>In the present study, we evaluated the relative abundance of angiotensin type 2 receptor (AT<jats:sub>2<\/jats:sub>R) protein in various tissues of adult rats. We found that pancreatic islets expressed the highest AT<jats:sub>2<\/jats:sub>R protein compared with all other tissues. Accordingly, we then determined the functional significance of AT<jats:sub>2<\/jats:sub>R in the endocrine pancreas in in vivo and in vitro experiments by using angiotensin II (ANG II) alone, losartan (Los; AT<jats:sub>1<\/jats:sub>R antagonist), compound 21 (C21; AT<jats:sub>2<\/jats:sub>R agonist), and PD-123319 (PD; AT<jats:sub>2<\/jats:sub>R antagonist). Experiments carried out in rats indicated that, 1) ANG II treatment significantly increased plasma insulin concentration (1.51 \u00b1 0.20 vs. 0.82 \u00b1 0.14 ng\/ml, n = 7, P &lt; 0.05) in the fed state. This insulinotropic effect was further augmented by combined treatment with ANG II + Los (2.31 \u00b1 0.25 ng\/ml, n = 7, P &lt; 0.01). C21 also elevated insulin levels (2.13 \u00b1 0.20 ng\/ml, n = 7, P &lt; 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<jats:sub>2<\/jats:sub>R activation significantly improved insulin biosynthesis and secretion. These results suggest that the AT<jats:sub>2<\/jats:sub>R functions as an insulinotropic mediator. AT<jats:sub>2<\/jats:sub>R and its downstream signaling pathways may be potential therapeutic targets for diabetes.<\/jats:p>","DOI":"10.1152\/ajpendo.00286.2013","type":"journal-article","created":{"date-parts":[[2013,10,2]],"date-time":"2013-10-02T01:59:26Z","timestamp":1380679166000},"page":"E1281-E1291","source":"Crossref","is-referenced-by-count":28,"title":["Angiotensin type 2 receptor in pancreatic islets of adult rats: a novel insulinotropic mediator"],"prefix":"10.1152","volume":"305","author":[{"given":"Chunhong","family":"Shao","sequence":"first","affiliation":[{"name":"Department of Cellular and Integrative Physiology, University of Nebraska Medical Center, Omaha, Nebraska"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Irving H.","family":"Zucker","sequence":"additional","affiliation":[{"name":"Department of Cellular and Integrative Physiology, University of Nebraska Medical Center, Omaha, 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