{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T19:37:04Z","timestamp":1790192224037,"version":"4.1.0"},"reference-count":53,"publisher":"American Society for Clinical Investigation","issue":"12","funder":[{"DOI":"10.13039\/100000062","name":"NIDDK","doi-asserted-by":"crossref","award":["DK074970,DK107444"],"award-info":[{"award-number":["DK074970,DK107444"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"crossref"}]},{"name":"NICHD","award":["HD044405"],"award-info":[{"award-number":["HD044405"]}]},{"DOI":"10.13039\/100000738","name":"U.S. Department of Veterans Affairs","doi-asserted-by":"crossref","award":["BX003725"],"award-info":[{"award-number":["BX003725"]}],"id":[{"id":"10.13039\/100000738","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2018,6,21]]},"abstract":"<jats:p>Androgen excess predisposes women to type 2 diabetes (T2D), but the mechanism of this is poorly understood. We report that female mice fed a Western diet and exposed to chronic androgen excess using dihydrotestosterone (DHT) exhibit hyperinsulinemia and insulin resistance associated with secondary pancreatic \u03b2 cell failure, leading to hyperglycemia. These abnormalities are not observed in mice lacking the androgen receptor (AR) in \u03b2 cells and partially in neurons of the mediobasal hypothalamus (MBH) as well as in mice lacking AR selectively in neurons. Accordingly, i.c.v. infusion of DHT produces hyperinsulinemia and insulin resistance in female WT mice. We observe that acute DHT produces insulin hypersecretion in response to glucose in cultured female mouse and human pancreatic islets in an AR-dependent manner via a cAMP- and mTOR-dependent pathway. Acute DHT exposure increases mitochondrial respiration and oxygen consumption in female cultured islets. As a result, chronic DHT exposure in vivo promotes islet oxidative damage and susceptibility to additional stress induced by streptozotocin via AR in \u03b2 cells. This study suggests that excess androgen predisposes female mice to T2D following AR activation in neurons, producing peripheral insulin resistance, and in pancreatic \u03b2 cells, promoting insulin hypersecretion, oxidative injury, and secondary \u03b2 cell failure.<\/jats:p>","DOI":"10.1172\/jci.insight.98607","type":"journal-article","created":{"date-parts":[[2018,6,20]],"date-time":"2018-06-20T11:01:31Z","timestamp":1529492491000},"source":"Crossref","is-referenced-by-count":74,"title":["Androgen excess in pancreatic \u03b2 cells and neurons predisposes female mice to type 2 diabetes"],"prefix":"10.1172","volume":"3","author":[{"given":"Guadalupe","family":"Navarro","sequence":"first","affiliation":[{"name":"Department of Medicine, Division of Endocrinology, Metabolism and Molecular Medicine, Northwestern University, Feinberg School of Medicine, Chicago, Illinois, 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