{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,4]],"date-time":"2026-02-04T18:19:23Z","timestamp":1770229163910,"version":"3.49.0"},"reference-count":30,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T00:00:00Z","timestamp":1770076800000},"content-version":"vor","delay-in-days":704,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2024,2,16]],"date-time":"2024-02-16T00:00:00Z","timestamp":1708041600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100001250","name":"Morris Animal Foundation","doi-asserted-by":"publisher","award":["D19-EQ-302"],"award-info":[{"award-number":["D19-EQ-302"]}],"id":[{"id":"10.13039\/100001250","id-type":"DOI","asserted-by":"publisher"}]},{"name":"The University of Queensland Graduate School Research Training Program (RTP) Scholarship"},{"name":"Destination Australia Scholarship"},{"name":"Open access publishing facilitated by The University of Queensland, as part of the Wiley - The University of Queensland agreement via the Council of Australian University Librarians."},{"DOI":"10.13039\/100001250","name":"Morris Animal Foundation","doi-asserted-by":"publisher","award":["D19\u2010EQ\u2010302"],"award-info":[{"award-number":["D19\u2010EQ\u2010302"]}],"id":[{"id":"10.13039\/100001250","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2024,3,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Phenylbutazone is often prescribed to manage pain caused by hyperinsulinemia-associated laminitis, but in diabetic people nonsteroidal anti-inflammatory drugs increase insulin secretion and pancreatic activity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Hypothesis\/Objectives<\/jats:title>\n                    <jats:p>Investigate the effect of phenylbutazone administration on insulin secretion in horses. It was hypothesized that phenylbutazone will increase insulin secretion in horses with insulin dysregulation (ID).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Animals<\/jats:title>\n                    <jats:p>Sixteen light breed horses, including 7 with ID.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Randomized cross-over study design. Horses underwent an oral glucose test (OGT) after 9\u2009days of treatment with phenylbutazone (4.4\u2009mg\/kg IV q24h) or placebo (5\u2009mL 0.9% saline). After a 10-day washout period, horses received the alternative treatment, and a second OGT was performed. Insulin and glucose responses were compared between groups (ID or controls) and treatments using paired t test and analyses of variance with P\u2009&amp;lt;\u2009.05 considered significant.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In horses with ID, phenylbutazone treatment significantly decreased glucose concentration (P\u2009=\u2009.02), glucose area under the curve (2429\u2009\u00b1\u2009501.5 vs 2847\u2009\u00b1\u2009486.1\u2009mmol\/L\u2009\u00d7\u2009min, P\u2009=\u2009.02), insulin concentration (P\u2009=\u2009.03) and insulin area under the curve (17\u2009710\u2009\u00b1\u20096676 vs 22\u2009930\u2009\u00b1\u20098788\u2009\u03bcIU\/mL\u2009\u00d7\u2009min, P\u2009=\u2009.03) in response to an OGT. No significant effect was detected in control horses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion and Clinical Importance<\/jats:title>\n                    <jats:p>Phenylbutazone administration in horses with ID decreases glucose and insulin concentrations in response to an OGT warranting further investigation of a therapeutic potential of phenylbutazone in the management of hyperinsulinemia-associated laminitis beyond analgesia.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/jvim.17013","type":"journal-article","created":{"date-parts":[[2024,2,16]],"date-time":"2024-02-16T07:44:51Z","timestamp":1708069491000},"page":"1177-1184","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Effect of phenylbutazone on insulin secretion in horses with insulin dysregulation"],"prefix":"10.1093","volume":"38","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"}]},{"given":"Jazmine E.","family":"Skinner","sequence":"additional","affiliation":[{"name":"School of Agriculture and Environmental Science, University of Southern Queensland , Darling Heights, Queensland,","place":["Australia"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2820-8431","authenticated-orcid":false,"given":"Fran\u00e7ois-Ren\u00e9","family":"Bertin","sequence":"additional","affiliation":[{"name":"School of Veterinary Science, The University of Queensland , Gatton, Queensland,","place":["Australia"]},{"name":"College of Veterinary Medicine, Purdue University , West-Lafayette, Indiana,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2024,3,1]]},"reference":[{"key":"2026020304074118700_jvim17013-bib-0001","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1111\/evj.12169","article-title":"Insulin dysregulation","volume":"46","author":"Frank","year":"2014","journal-title":"Equine Vet J"},{"key":"2026020304074118700_jvim17013-bib-0002","doi-asserted-by":"crossref","first-page":"E61","DOI":"10.1152\/ajpendo.00362.2015","article-title":"Equine hyperinsulinemia: investigation of the enteroinsular axis during insulin dysregulation","volume":"310","author":"de Laat","year":"2016","journal-title":"Am J Physiol-Endocrinol Metab"},{"key":"2026020304074118700_jvim17013-bib-0003","doi-asserted-by":"crossref","first-page":"129","DOI":"10.2746\/042516409X475779","article-title":"Equine laminitis: induced by 48 h hyperinsulinaemia in Standardbred horses","volume":"42","author":"de Laat","year":"2010","journal-title":"Equine Vet J"},{"key":"2026020304074118700_jvim17013-bib-0004","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1111\/evj.13224","article-title":"Lamellar energy metabolism and perfusion in the euglycaemic hyperinsulinaemic clamp model of equine laminitis","volume":"52","author":"Stokes","year":"2020","journal-title":"Equine Vet J"},{"key":"2026020304074118700_jvim17013-bib-0005","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1016\/j.cveq.2021.08.004","article-title":"Pharmacology of the equine medical pain management for laminitis","volume":"37","author":"Hopster","year":"2021","journal-title":"Vet Clin North Am Equine Pract"},{"key":"2026020304074118700_jvim17013-bib-0006","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/j.cveq.2009.12.011","article-title":"Acute laminitis: medical and supportive therapy","volume":"26","author":"van Eps","year":"2010","journal-title":"Vet Clin North Am Equine Pract"},{"key":"2026020304074118700_jvim17013-bib-0007","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/j.1365-2885.2011.01299.x","article-title":"The use of phenylbutazone in the horse","volume":"35","author":"Soma","year":"2012","journal-title":"J Vet Pharmacol Ther"},{"key":"2026020304074118700_jvim17013-bib-0008","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1016\/j.phrs.2005.04.004","article-title":"COX-1 and COX-2 inhibition in horse blood by phenylbutazone, flunixin, carprofen and meloxicam: an in vitro analysis","volume":"52","author":"Beretta","year":"2005","journal-title":"Pharmacol Res"},{"key":"2026020304074118700_jvim17013-bib-0009","doi-asserted-by":"crossref","first-page":"792","DOI":"10.1002\/dta.2553","article-title":"Phenylbutazone blood and urine concentrations, pharmacokinetics, and effects on biomarkers of inflammation in horses following intravenous and oral administration of clinical doses","volume":"11","author":"Knych","year":"2019","journal-title":"Drug Test Anal"},{"key":"2026020304074118700_jvim17013-bib-0010","doi-asserted-by":"crossref","first-page":"1904","DOI":"10.2337\/db12-0769","article-title":"Prostaglandin E2 receptor, EP3, is induced in diabetic islets and negatively regulates glucose- and hormone-stimulated insulin secretion","volume":"62","author":"Kimple","year":"2013","journal-title":"Diabetes"},{"key":"2026020304074118700_jvim17013-bib-0011","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1038\/sj.bjp.0707259","article-title":"Non-steroidal anti-inflammatory drugs increase insulin release from beta cells by inhibiting ATP-sensitive potassium channels: NSAIDs regulate insulin secretion","volume":"151","author":"Li","year":"2009","journal-title":"Br J Pharmacol"},{"key":"2026020304074118700_jvim17013-bib-0012","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1177\/0897190016649551","article-title":"Potential effects of nonsteroidal anti-inflammatory drugs in the prevention and treatment of type 2 diabetes mellitus","volume":"30","author":"Bellucci","year":"2017","journal-title":"J Pharm Pract"},{"key":"2026020304074118700_jvim17013-bib-0013","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1111\/j.2042-3306.1983.tb01826.x","article-title":"Relationship between condition score, physical measurements and body fat percentage in mares","volume":"15","author":"Henneke","year":"1983","journal-title":"Equine Vet J"},{"key":"2026020304074118700_jvim17013-bib-0014","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1016\/j.tvjl.2008.02.029","article-title":"Apparent adiposity assessed by standardised scoring systems and morphometric measurements in horses and ponies","volume":"179","author":"Carter","year":"2009","journal-title":"Vet J"},{"key":"2026020304074118700_jvim17013-bib-0015","doi-asserted-by":"crossref","first-page":"84","DOI":"10.2460\/ajvr.76.1.84","article-title":"Comparison among the euglycemic-hyperinsulinemic clamp, insulin-modified frequently sampled intravenous glucose tolerance test, and oral glucose tolerance test for assessment of insulin sensitivity in healthy Standardbreds","volume":"76","author":"Pratt-Phillips","year":"2015","journal-title":"Am J Vet Res"},{"key":"2026020304074118700_jvim17013-bib-0016","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1111\/evj.12579","article-title":"The repeatability of an oral glucose test in ponies","volume":"49","author":"de Laat","year":"2017","journal-title":"Equine Vet J"},{"key":"2026020304074118700_jvim17013-bib-0017","doi-asserted-by":"crossref","first-page":"932","DOI":"10.1111\/j.1939-1676.2010.0551.x","article-title":"Proinflammatory cytokine and chemokine gene expression profiles in subcutaneous and visceral adipose tissue depots of insulin-resistant and insulin-sensitive light breed horses","volume":"24","author":"Burns","year":"2010","journal-title":"J Vet Intern Med"},{"key":"2026020304074118700_jvim17013-bib-0018","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1111\/jvim.13934","article-title":"Evaluation of four diagnostic tests for insulin dysregulation in adult light-breed horses","volume":"30","author":"Dunbar","year":"2016","journal-title":"J Vet Intern Med"},{"key":"2026020304074118700_jvim17013-bib-0019","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1111\/j.1939-1676.2010.0481.x","article-title":"Evaluation of a veterinary glucometer for use in horses","volume":"24","author":"Hackett","year":"2010","journal-title":"J Vet Intern Med"},{"key":"2026020304074118700_jvim17013-bib-0020","doi-asserted-by":"crossref","first-page":"568","DOI":"10.1111\/jvim.14657","article-title":"Evaluation of a chemiluminescent immunoassay for measurement of equine insulin","volume":"31","author":"Carslake","year":"2017","journal-title":"J Vet Intern Med"},{"key":"2026020304074118700_jvim17013-bib-0021","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1111\/j.1365-2885.1984.tb00911.x","article-title":"Population distributions of phenylbutazone and oxyphenbutazone after oral and i.v. dosing in horses","volume":"7","author":"Chay","year":"1984","journal-title":"J Vet Pharmacol Ther"},{"key":"2026020304074118700_jvim17013-bib-0022","doi-asserted-by":"crossref","first-page":"743","DOI":"10.2460\/ajvr.1989.50.05.743","article-title":"Effects of phenylbutazone on glucose tolerance and on secretion of insulin in healthy geldings","volume":"50","author":"Zicker","year":"1989","journal-title":"Am J Vet Res"},{"key":"2026020304074118700_jvim17013-bib-0023","doi-asserted-by":"crossref","first-page":"842","DOI":"10.1111\/evj.12825","article-title":"Glucagon-like peptide-2: a potential role in equine insulin dysregulation","volume":"50","author":"de Laat","year":"2018","journal-title":"Equine Vet J"},{"key":"2026020304074118700_jvim17013-bib-0024","doi-asserted-by":"crossref","first-page":"1939","DOI":"10.1159\/000430162","article-title":"Enhanced glucose tolerance and pancreatic beta cell function by low dose aspirin in hyperglycemic insulin-resistant type 2 diabetic Goto-Kakizaki (GK) rats","volume":"36","author":"Amiri","year":"2015","journal-title":"Cell Physiol Biochem"},{"key":"2026020304074118700_jvim17013-bib-0025","doi-asserted-by":"crossref","first-page":"130","DOI":"10.2460\/ajvr.69.1.130","article-title":"Effects of systemic inflammation on insulin sensitivity in horses and inflammatory cytokine expression in adipose tissue","volume":"69","author":"Vick","year":"2008","journal-title":"Am J Vet Res"},{"key":"2026020304074118700_jvim17013-bib-0026","doi-asserted-by":"crossref","first-page":"243","DOI":"10.3390\/ani2020243","article-title":"A potential role for pro-inflammatory cytokines in the development of insulin resistance in horses","volume":"2","author":"Suagee","year":"2012","journal-title":"Animals"},{"key":"2026020304074118700_jvim17013-bib-0027","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.immuni.2021.12.013","article-title":"Inflammation in obesity, diabetes, and related disorders","volume":"55","author":"Rohm","year":"2022","journal-title":"Immunity"},{"key":"2026020304074118700_jvim17013-bib-0028","doi-asserted-by":"crossref","DOI":"10.3389\/fphar.2023.1117683","article-title":"Hypolipidemic and insulin sensitizing effects of salsalate beyond suppressing inflammation in a prediabetic rat model","volume":"14","author":"H\u00fcttl","year":"2023","journal-title":"Front Pharmacol"},{"key":"2026020304074118700_jvim17013-bib-0029","doi-asserted-by":"crossref","DOI":"10.1016\/j.bcp.2021.114557","article-title":"Valdecoxib improves lipid-induced skeletal muscle insulin resistance via simultaneous suppression of inflammation and endoplasmic reticulum stress","volume":"188","author":"Kim","year":"2021","journal-title":"Biochem Pharmacol"},{"key":"2026020304074118700_jvim17013-bib-0030","doi-asserted-by":"crossref","first-page":"570","DOI":"10.1111\/evj.12703","article-title":"The diagnosis of equine insulin dysregulation","volume":"49","author":"Bertin","year":"2017","journal-title":"Equine Vet J"}],"updated-by":[{"DOI":"10.1111\/jvim.17210","type":"erratum","label":"Erratum","source":"publisher","updated":{"date-parts":[[2024,10,7]],"date-time":"2024-10-07T00:00:00Z","timestamp":1728259200000}}],"container-title":["Journal of Veterinary Internal Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jvim\/article-pdf\/38\/2\/1177\/66664957\/jvim17013.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jvim\/article-pdf\/38\/2\/1177\/66664957\/jvim17013.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T09:07:55Z","timestamp":1770109675000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jvim\/article\/38\/2\/1177\/8448867"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,3,1]]},"references-count":30,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2024,3,1]]}},"URL":"https:\/\/doi.org\/10.1111\/jvim.17013","relation":{},"ISSN":["1939-1676"],"issn-type":[{"value":"1939-1676","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2024,3]]},"published":{"date-parts":[[2024,3,1]]},"assertion":[{"value":"2023-11-01","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-01-26","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-02-16","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}