{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T18:47:56Z","timestamp":1789757276504,"version":"4.0.1"},"reference-count":48,"publisher":"National Academy of Sciences","issue":"10","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2014,3,11]]},"abstract":"<jats:title>Significance<\/jats:title>\n                  <jats:p>Prevalence of chronic kidney disease (CKD) has reached epidemic proportions in the Western world in recent decades. Abnormally elevated blood insulin and impaired insulin action (insulin resistance) are common complications of CKD, and are associated with increased cardiovascular-related deaths in CKD patients. Therefore, novel therapies are required to treat insulin resistance in CKD. Abnormally elevated levels of glucocorticoids can cause insulin resistance. Here we demonstrate a crucial role for the enzyme 11\u03b2-hydroxysteroid dehydrogenase type 1 (11\u03b2HSD1) predominantly in liver, which is essential for glucocorticoid production, in causing insulin resistance in CKD. Additionally, 11\u03b2HSD1 inhibition corrected insulin resistance in CKD rodent models. Taken together, this is strong evidence that selective inhibition of 11\u03b2HSD1 is a promising therapeutic target for treatment of insulin resistance in CKD.<\/jats:p>","DOI":"10.1073\/pnas.1312436111","type":"journal-article","created":{"date-parts":[[2014,2,26]],"date-time":"2014-02-26T00:04:05Z","timestamp":1393373045000},"page":"3817-3822","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":31,"title":["Elevated hepatic 11\u03b2-hydroxysteroid dehydrogenase type 1 induces insulin resistance in uremia"],"prefix":"10.1073","volume":"111","author":[{"given":"Ananda","family":"Chapagain","sequence":"first","affiliation":[{"name":"Centre of Translational Medicine and Therapeutics, William Harvey Research Institute, Barts and the London, Queen Mary University of London, London EC1M 6BQ, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul W.","family":"Caton","sequence":"additional","affiliation":[{"name":"Centre for Diabetes, Blizard Institute, Barts and the London, Queen Mary University of London, London E1 2AT, United Kingdom; 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