{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T15:42:28Z","timestamp":1791042148234,"version":"4.1.0"},"reference-count":50,"publisher":"American Diabetes Association","issue":"4","license":[{"start":{"date-parts":[[2021,8,27]],"date-time":"2021-08-27T00:00:00Z","timestamp":1630022400000},"content-version":"vor","delay-in-days":3453,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/3.0\/"}],"content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2012,4,1]]},"abstract":"<jats:sec>\n                  <jats:title\/>\n                  <jats:p>Recent trials show salicylates improve glycemic control in type 2 diabetes, but the mechanism is poorly understood. Expression of the glucocorticoid-generating enzyme 11\u03b2-hydroxysteroid dehydrogenase type 1 (11\u03b2-HSD1) in adipose tissue is increased in vitro by proinflammatory cytokines and upregulated in obesity. 11\u03b2-HSD1 inhibition enhances insulin sensitivity. We hypothesized that salicylates downregulate 11\u03b2-HSD1 expression, contributing to their metabolic efficacy. We treated diet-induced obese (DIO) 11\u03b2-HSD1\u2013deficient mice and C57Bl\/6 mice with sodium salicylate for 4 weeks. Glucose tolerance was assessed in vivo. Tissue transcript levels were assessed by quantitative PCR and enzyme activity by incubation with 3H-steroid. Two weeks\u2019 administration of salsalate was also investigated in a randomized double-blind placebo-controlled crossover study in 16 men, with measurement of liver 11\u03b2-HSD1 activity in vivo and adipose tissue 11\u03b2-HSD1 transcript levels ex vivo. In C57Bl\/6 DIO mice, salicylate improved glucose tolerance and downregulated 11\u03b2-HSD1 mRNA and activity selectively in visceral adipose. DIO 11\u03b2-HSD1\u2013deficient mice were resistant to these metabolic effects of salicylate. In men, salsalate reduced 11\u03b2-HSD1 expression in subcutaneous adipose, and in vitro salicylate treatment reduced adipocyte 11\u03b2-HSD1 expression and induced adiponectin expression only in the presence of 11\u03b2-HSD1 substrate. Reduced intra-adipose glucocorticoid regeneration by 11\u03b2-HSD1 is a novel mechanism that contributes to the metabolic efficacy of salicylates.<\/jats:p>\n               <\/jats:sec>","DOI":"10.2337\/db11-0931","type":"journal-article","created":{"date-parts":[[2012,2,23]],"date-time":"2012-02-23T01:31:36Z","timestamp":1329960696000},"page":"790-796","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":56,"title":["Salicylate Downregulates 11\u03b2-HSD1 Expression in Adipose Tissue in Obese Mice and in Humans, Mediating Insulin Sensitization"],"prefix":"10.2337","volume":"61","author":[{"given":"Mark","family":"Nixon","sequence":"first","affiliation":[{"name":"Endocrinology Unit, Centre for Cardiovascular Science, University of Edinburgh, Queen\u2019s Medical Research Institute, Edinburgh, Scotland, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deborah J.","family":"Wake","sequence":"additional","affiliation":[{"name":"Endocrinology Unit, Centre for Cardiovascular Science, University of Edinburgh, Queen\u2019s Medical Research Institute, Edinburgh, Scotland, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dawn E.","family":"Livingstone","sequence":"additional","affiliation":[{"name":"Endocrinology Unit, Centre for Cardiovascular Science, University of Edinburgh, Queen\u2019s Medical Research Institute, Edinburgh, Scotland, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roland H.","family":"Stimson","sequence":"additional","affiliation":[{"name":"Endocrinology Unit, Centre for Cardiovascular Science, University of Edinburgh, Queen\u2019s Medical Research Institute, Edinburgh, Scotland, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina L.","family":"Esteves","sequence":"additional","affiliation":[{"name":"Endocrinology Unit, Centre for Cardiovascular Science, University of Edinburgh, Queen\u2019s Medical Research Institute, Edinburgh, Scotland, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan R.","family":"Seckl","sequence":"additional","affiliation":[{"name":"Endocrinology Unit, Centre for Cardiovascular Science, University of Edinburgh, Queen\u2019s Medical Research Institute, Edinburgh, Scotland, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen E.","family":"Chapman","sequence":"additional","affiliation":[{"name":"Endocrinology Unit, Centre for Cardiovascular Science, University of Edinburgh, Queen\u2019s Medical Research Institute, Edinburgh, Scotland, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruth","family":"Andrew","sequence":"additional","affiliation":[{"name":"Endocrinology Unit, Centre for Cardiovascular Science, University of Edinburgh, Queen\u2019s Medical Research Institute, Edinburgh, Scotland, 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