Effect of phenylbutazone administration on the enteroinsular axis in horses with insulin dysregulation

Abstract Background Phenylbutazone is prescribed for laminitis‐associated pain and decreases glucose and insulin responses to an oral glucose test (OGT) in horses with insulin dysregulation (ID). Hypothesis/Objectives Investigate the effect of phenylbutazone administration on the enteroinsular axis...

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Main Authors: Kate L. Kemp, Jazmine E. Skinner, François‐René Bertin
Format: Article
Language:English
Published: Wiley 2025-01-01
Series:Journal of Veterinary Internal Medicine
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Online Access:https://doi.org/10.1111/jvim.17256
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author Kate L. Kemp
Jazmine E. Skinner
François‐René Bertin
author_facet Kate L. Kemp
Jazmine E. Skinner
François‐René Bertin
author_sort Kate L. Kemp
collection DOAJ
description Abstract Background Phenylbutazone is prescribed for laminitis‐associated pain and decreases glucose and insulin responses to an oral glucose test (OGT) in horses with insulin dysregulation (ID). Hypothesis/Objectives Investigate the effect of phenylbutazone administration on the enteroinsular axis in horses. Animals Sixteen horses, including 7 with ID. Methods Randomized cross‐over study design, with horses assigned to treatment with phenylbutazone (4.4 mg/kg IV q24h) or placebo (5 mL 0.9% saline). On Day 9 of treatment, an OGT was conducted, followed by a 10‐day washout period, administration of the alternative treatment, and repetition of the OGT. Glucose‐dependent insulinotropic polypeptide (GIP), and active glucagon‐like peptide 1 and 2 (aGLP‐1 and GLP‐2) concentrations were determined by ELISA. The effects of ID status and treatment on peptide concentrations were assessed using t tests and analyses of variance. Results Horses with ID had significantly higher maximum GIP concentrations (Cmax) than controls (median, 279.1; interquartile range [IQR], 117.5‐319.4 pg/mL vs median, 90.12; IQR, 74.62‐116.5 pg/mL; P = .01), but no significant effect of ID was detected on aGLP‐1 and GLP‐2 concentrations. In horses with ID, phenylbutazone treatment significantly decreased GIP Cmax compared with placebo (168.1 ± 59.26 pg/mL vs 242.8 ± 121.8 pg/mL; P = .04), but no significant effect of phenylbutazone was detected on aGLP‐1 and GLP‐2 concentrations. Conclusion and Clinical Importance Glucose‐dependent insulinotropic polypeptide, aGLP‐1 and GLP‐2 do not mediate the decrease in glucose and insulin concentrations observed after phenylbutazone administration. Only GIP was repeatedly associated with ID status, calling into question the role of the enteroinsular axis in ID.
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spelling doaj-art-fe3eae22d0b5448e8eadd2a8f5517b912025-01-27T15:22:40ZengWileyJournal of Veterinary Internal Medicine0891-66401939-16762025-01-01391n/an/a10.1111/jvim.17256Effect of phenylbutazone administration on the enteroinsular axis in horses with insulin dysregulationKate L. Kemp0Jazmine E. Skinner1François‐René Bertin2School of Veterinary Science The University of Queensland, 5391 Warrego Hwy Gatton Queensland 4343 AustraliaSchool of Agriculture and Environmental Science University of Southern Queensland, 487 – 35 West St Darling Heights Queensland 4350 AustraliaSchool of Veterinary Science The University of Queensland, 5391 Warrego Hwy Gatton Queensland 4343 AustraliaAbstract Background Phenylbutazone is prescribed for laminitis‐associated pain and decreases glucose and insulin responses to an oral glucose test (OGT) in horses with insulin dysregulation (ID). Hypothesis/Objectives Investigate the effect of phenylbutazone administration on the enteroinsular axis in horses. Animals Sixteen horses, including 7 with ID. Methods Randomized cross‐over study design, with horses assigned to treatment with phenylbutazone (4.4 mg/kg IV q24h) or placebo (5 mL 0.9% saline). On Day 9 of treatment, an OGT was conducted, followed by a 10‐day washout period, administration of the alternative treatment, and repetition of the OGT. Glucose‐dependent insulinotropic polypeptide (GIP), and active glucagon‐like peptide 1 and 2 (aGLP‐1 and GLP‐2) concentrations were determined by ELISA. The effects of ID status and treatment on peptide concentrations were assessed using t tests and analyses of variance. Results Horses with ID had significantly higher maximum GIP concentrations (Cmax) than controls (median, 279.1; interquartile range [IQR], 117.5‐319.4 pg/mL vs median, 90.12; IQR, 74.62‐116.5 pg/mL; P = .01), but no significant effect of ID was detected on aGLP‐1 and GLP‐2 concentrations. In horses with ID, phenylbutazone treatment significantly decreased GIP Cmax compared with placebo (168.1 ± 59.26 pg/mL vs 242.8 ± 121.8 pg/mL; P = .04), but no significant effect of phenylbutazone was detected on aGLP‐1 and GLP‐2 concentrations. Conclusion and Clinical Importance Glucose‐dependent insulinotropic polypeptide, aGLP‐1 and GLP‐2 do not mediate the decrease in glucose and insulin concentrations observed after phenylbutazone administration. Only GIP was repeatedly associated with ID status, calling into question the role of the enteroinsular axis in ID.https://doi.org/10.1111/jvim.17256endocrinologyequine metabolic syndromehyperinsulinemialaminitisnon‐steroidal anti‐inflammatory drugsobesity
spellingShingle Kate L. Kemp
Jazmine E. Skinner
François‐René Bertin
Effect of phenylbutazone administration on the enteroinsular axis in horses with insulin dysregulation
Journal of Veterinary Internal Medicine
endocrinology
equine metabolic syndrome
hyperinsulinemia
laminitis
non‐steroidal anti‐inflammatory drugs
obesity
title Effect of phenylbutazone administration on the enteroinsular axis in horses with insulin dysregulation
title_full Effect of phenylbutazone administration on the enteroinsular axis in horses with insulin dysregulation
title_fullStr Effect of phenylbutazone administration on the enteroinsular axis in horses with insulin dysregulation
title_full_unstemmed Effect of phenylbutazone administration on the enteroinsular axis in horses with insulin dysregulation
title_short Effect of phenylbutazone administration on the enteroinsular axis in horses with insulin dysregulation
title_sort effect of phenylbutazone administration on the enteroinsular axis in horses with insulin dysregulation
topic endocrinology
equine metabolic syndrome
hyperinsulinemia
laminitis
non‐steroidal anti‐inflammatory drugs
obesity
url https://doi.org/10.1111/jvim.17256
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AT francoisrenebertin effectofphenylbutazoneadministrationontheenteroinsularaxisinhorseswithinsulindysregulation