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Phenylbutazone reduces glucose and insulin concentrations in horses with insulin dysregulation (ID) but the underlying mechanism of action is unknown.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Hypothesis\/Objectives<\/jats:title>\n                    <jats:p>Investigate the effect of phenylbutazone on tissue insulin sensitivity in horses. It is hypothesized that the reduced glucose and insulin concentrations in horses with ID receiving phenylbutazone are mediated by a higher tissue insulin sensitivity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Animals<\/jats:title>\n                    <jats:p>Fifteen light breed horses, including seven with ID.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Randomized cross-over study. Horses underwent a modified frequently sampled intravenous glucose tolerance test (mFSIGTT) after 8\u2009days of treatment with phenylbutazone (4.4\u2009mg\/kg IV daily) or placebo (5\u2009mL 0.9% saline IV daily). After a 10-day washout period, horses received the alternative treatment for 8\u2009days and a second mFSIGTT. Minimal model analysis was performed, and the effects of ID status and phenylbutazone were investigated with p\u2009&amp;lt;\u20090.05 considered significant.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In horses with ID, phenylbutazone increased tissue insulin sensitivity index (median [interquartile range]: 0.39 [0.14\u20130.74] vs. 0.56 [0.55\u20131.18] \u00d710\u22124 L\/mIU\/min, p\u2009=\u20090.03), and decreased glucose (21\u2009726 [19\u2009040\u201324\u2009948] vs. 22\u2009909 [22\u2009496\u201326\u2009166] mg\/dL\u2009\u00d7\u2009min, p\u2009=\u20090.02) and insulin (19\u2009595 [16\u2009147\u201429\u2009698] vs. 22\u2009752 [20\u2009578\u201431\u2009826] \u03bcIU\/mL\u2009\u00d7\u2009min, p\u2009=\u20090.03) areas under the curves. No effect was detected in horses administered placebo.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion and Clinical Importance<\/jats:title>\n                    <jats:p>Phenylbutazone reduces insulin concentration in horses with ID by modulating tissue insulin sensitivity, suggesting that its relevance in the management of ID can extend beyond laminitis-associated pain.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/jvim.70028","type":"journal-article","created":{"date-parts":[[2025,3,10]],"date-time":"2025-03-10T18:54:08Z","timestamp":1741632848000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Effect of Phenylbutazone Administration on Insulin Sensitivity in Horses With Insulin Dysregulation"],"prefix":"10.1093","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8867-5210","authenticated-orcid":false,"given":"Kate L.","family":"Kemp","sequence":"first","affiliation":[{"name":"School of Veterinary Science, The University of Queensland , Gatton, Queensland,","place":["Australia"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7406-8102","authenticated-orcid":false,"given":"Nicholas K. 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