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

Article

Kemp, Kate L., Skinner, Jazmine E. and Bertin, Francois-Rene. 2025. "Effect of phenylbutazone administration on the enteroinsular axis in horses with insulin dysregulation." Journal of Veterinary Internal Medicine. 39 (1). https://doi.org/10.1111/jvim.17256
Article Title

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

ERA Journal ID5528
Article CategoryArticle
AuthorsKemp, Kate L., Skinner, Jazmine E. and Bertin, Francois-Rene
Journal TitleJournal of Veterinary Internal Medicine
Journal Citation39 (1)
Article Numbere17256
Number of Pages9
Year2025
PublisherJohn Wiley & Sons
Place of PublicationUnited States
ISSN0891-6640
1939-1676
Digital Object Identifier (DOI)https://doi.org/10.1111/jvim.17256
Web Address (URL)https://onlinelibrary.wiley.com/doi/10.1111/jvim.17256
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.

Keywordsendocrinology; equine metabolic syndrome; hyperinsulinemia; laminitis; non-steroidal antiinflammatory drugs; obesity; oral glucose test
Contains Sensitive ContentDoes not contain sensitive content
ANZSRC Field of Research 2020300301. Animal growth and development
Byline AffiliationsUniversity of Queensland
School of Agriculture and Environmental Science
Purdue University, United States
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