Effect of Phenylbutazone Administration on Insulin Sensitivity in Horses With Insulin Dysregulation

ABSTRACT Background Phenylbutazone is prescribed to manage pain caused by hyperinsulinemia‐associated laminitis. Phenylbutazone reduces glucose and insulin concentrations in horses with insulin dysregulation (ID) but the underlying mechanism of action is unknown. Hypothesis/Objectives Investigate th...

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Main Authors: Kate L. Kemp, Nicholas K. Y. Yuen, Jazmine E. Skinner, François‐René Bertin
Format: Article
Language:English
Published: Wiley 2025-03-01
Series:Journal of Veterinary Internal Medicine
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Online Access:https://doi.org/10.1111/jvim.70028
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author Kate L. Kemp
Nicholas K. Y. Yuen
Jazmine E. Skinner
François‐René Bertin
author_facet Kate L. Kemp
Nicholas K. Y. Yuen
Jazmine E. Skinner
François‐René Bertin
author_sort Kate L. Kemp
collection DOAJ
description ABSTRACT Background Phenylbutazone is prescribed to manage pain caused by hyperinsulinemia‐associated laminitis. Phenylbutazone reduces glucose and insulin concentrations in horses with insulin dysregulation (ID) but the underlying mechanism of action is unknown. Hypothesis/Objectives 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. Animals Fifteen light breed horses, including seven with ID. Methods Randomized cross‐over study. Horses underwent a modified frequently sampled intravenous glucose tolerance test (mFSIGTT) after 8 days of treatment with phenylbutazone (4.4 mg/kg IV daily) or placebo (5 mL 0.9% saline IV daily). After a 10‐day washout period, horses received the alternative treatment for 8 days and a second mFSIGTT. Minimal model analysis was performed, and the effects of ID status and phenylbutazone were investigated with p < 0.05 considered significant. Results In horses with ID, phenylbutazone increased tissue insulin sensitivity index (median [interquartile range]: 0.39 [0.14–0.74] vs. 0.56 [0.55–1.18] ×10−4 L/mIU/min, p = 0.03), and decreased glucose (21 726 [19 040–24 948] vs. 22 909 [22 496–26 166] mg/dL × min, p = 0.02) and insulin (19 595 [16 147—29 698] vs. 22 752 [20 578—31 826] μIU/mL × min, p = 0.03) areas under the curves. No effect was detected in horses administered placebo. Conclusion and Clinical Importance 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.
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spelling doaj-art-29b5e97841124508a00775abe50e68322025-08-20T03:48:56ZengWileyJournal of Veterinary Internal Medicine0891-66401939-16762025-03-01392n/an/a10.1111/jvim.70028Effect of Phenylbutazone Administration on Insulin Sensitivity in Horses With Insulin DysregulationKate L. Kemp0Nicholas K. Y. Yuen1Jazmine E. Skinner2François‐René Bertin3School of Veterinary Science The University of Queensland Gatton Queensland AustraliaSchool of Veterinary Science The University of Queensland Gatton Queensland AustraliaSchool of Agriculture and Environmental Science University of Southern Queensland Queensland AustraliaSchool of Veterinary Science The University of Queensland Gatton Queensland AustraliaABSTRACT Background Phenylbutazone is prescribed to manage pain caused by hyperinsulinemia‐associated laminitis. Phenylbutazone reduces glucose and insulin concentrations in horses with insulin dysregulation (ID) but the underlying mechanism of action is unknown. Hypothesis/Objectives 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. Animals Fifteen light breed horses, including seven with ID. Methods Randomized cross‐over study. Horses underwent a modified frequently sampled intravenous glucose tolerance test (mFSIGTT) after 8 days of treatment with phenylbutazone (4.4 mg/kg IV daily) or placebo (5 mL 0.9% saline IV daily). After a 10‐day washout period, horses received the alternative treatment for 8 days and a second mFSIGTT. Minimal model analysis was performed, and the effects of ID status and phenylbutazone were investigated with p < 0.05 considered significant. Results In horses with ID, phenylbutazone increased tissue insulin sensitivity index (median [interquartile range]: 0.39 [0.14–0.74] vs. 0.56 [0.55–1.18] ×10−4 L/mIU/min, p = 0.03), and decreased glucose (21 726 [19 040–24 948] vs. 22 909 [22 496–26 166] mg/dL × min, p = 0.02) and insulin (19 595 [16 147—29 698] vs. 22 752 [20 578—31 826] μIU/mL × min, p = 0.03) areas under the curves. No effect was detected in horses administered placebo. Conclusion and Clinical Importance 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.https://doi.org/10.1111/jvim.70028endocrinologyequine metabolic syndromeinsulin resistancelaminitisnon‐steroidal anti‐inflammatory drugsobesity
spellingShingle Kate L. Kemp
Nicholas K. Y. Yuen
Jazmine E. Skinner
François‐René Bertin
Effect of Phenylbutazone Administration on Insulin Sensitivity in Horses With Insulin Dysregulation
Journal of Veterinary Internal Medicine
endocrinology
equine metabolic syndrome
insulin resistance
laminitis
non‐steroidal anti‐inflammatory drugs
obesity
title Effect of Phenylbutazone Administration on Insulin Sensitivity in Horses With Insulin Dysregulation
title_full Effect of Phenylbutazone Administration on Insulin Sensitivity in Horses With Insulin Dysregulation
title_fullStr Effect of Phenylbutazone Administration on Insulin Sensitivity in Horses With Insulin Dysregulation
title_full_unstemmed Effect of Phenylbutazone Administration on Insulin Sensitivity in Horses With Insulin Dysregulation
title_short Effect of Phenylbutazone Administration on Insulin Sensitivity in Horses With Insulin Dysregulation
title_sort effect of phenylbutazone administration on insulin sensitivity in horses with insulin dysregulation
topic endocrinology
equine metabolic syndrome
insulin resistance
laminitis
non‐steroidal anti‐inflammatory drugs
obesity
url https://doi.org/10.1111/jvim.70028
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AT nicholaskyyuen effectofphenylbutazoneadministrationoninsulinsensitivityinhorseswithinsulindysregulation
AT jazmineeskinner effectofphenylbutazoneadministrationoninsulinsensitivityinhorseswithinsulindysregulation
AT francoisrenebertin effectofphenylbutazoneadministrationoninsulinsensitivityinhorseswithinsulindysregulation