Effect of phenylbutazone administration on the enteroinsular axis in horses with insulin dysregulation.
Authors: Kemp Kate L, Skinner Jazmine E, Bertin François-René
Journal: Journal of veterinary internal medicine
Summary
# Editorial Summary Phenylbutazone is commonly prescribed to manage pain in laminitis cases and has been shown to lower glucose and insulin responses during oral glucose testing in horses with insulin dysregulation (ID), yet the mechanism underlying this effect remains unclear. Researchers administered phenylbutazone (4.4 mg/kg intravenously daily) or placebo to 16 horses—seven with ID and nine controls—in a randomised crossover design, conducting oral glucose tests on day 9 of each treatment phase and measuring enteroinsular peptide responses (GIP, aGLP-1, and GLP-2) via ELISA. Horses with ID demonstrated significantly elevated peak GIP concentrations compared with controls (median 279.1 versus 90.12 pg/mL), but phenylbutazone treatment substantially suppressed this GIP response in dysregulated horses (168.1 pg/mL versus 242.8 pg/mL under placebo), whilst neither aGLP-1 nor GLP-2 concentrations were meaningfully altered by treatment or ID status. These findings suggest that the glucose and insulin-lowering effects of phenylbutazone in horses with ID are not mediated through the incretin axis, instead implying that GIP dysregulation may be a marker rather than a driver of insulin dysregulation, which has important implications for understanding the underlying pathophysiology and developing future therapeutic strategies for this condition.
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Practical Takeaways
- •Phenylbutazone reduces GIP concentrations in horses with insulin dysregulation, but this does not explain its glucose and insulin-lowering effects, suggesting alternative mechanisms of action
- •The enteroinsular axis hormones measured (GIP, GLP-1, GLP-2) appear not to play a primary role in insulin dysregulation or phenylbutazone's therapeutic effects in affected horses
- •Clinicians using phenylbutazone for laminitis pain in insulin dysregulated horses may see metabolic improvements, but further research is needed to understand the underlying mechanisms
Key Findings
- •Horses with insulin dysregulation had significantly higher maximum GIP concentrations (median 279.1 pg/mL) compared to controls (median 90.12 pg/mL; P = 0.01)
- •Phenylbutazone treatment in horses with ID significantly decreased GIP Cmax compared to placebo (168.1 pg/mL vs 242.8 pg/mL; P = 0.04)
- •Phenylbutazone had no significant effect on aGLP-1 and GLP-2 concentrations in horses with ID
- •GIP, aGLP-1, and GLP-2 do not mediate the glucose and insulin-lowering effects of phenylbutazone administration