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Journal of veterinary internal medicine2024; 39(1); e17256; doi: 10.1111/jvim.17256

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

Abstract: 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). Objective: Investigate the effect of phenylbutazone administration on the enteroinsular axis in horses. Methods: 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. Conclusions: 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.
Publication Date: 2024-11-22 PubMed ID: 39578373PubMed Central: PMC11627515DOI: 10.1111/jvim.17256Google Scholar: Lookup
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  • Journal Article

Summary

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This is a study about the impact of medication Phenylbutazone on horses suffering from insulin dysregulation. It suggests that only Glucose-dependent insulinotropic polypeptide (GIP) seems to be associated with insulin dysregulation (ID) status, while other peptides are not involved.

Methodology

  • This study included 16 horses, of which 7 had insulin dysregulation (ID). The experiment was conducted following a randomized cross-over study design.
  • The horses selected were subjected to treatment with phenylbutazone or a placebo. The dosage of phenylbutazone prescribed was 4.4 mg/kg IV q24h while the placebo horses were given 5 mL 0.9% saline.
  • After nine days of treatment, the horses underwent an oral glucose test (OGT), which was followed by a 10-day washout period.
  • Post this, the alternative treatment was administered and the OGT was repeated.
  • The study measured the concentrations of Glucose-dependent insulinotropic polypeptide (GIP), and active glucagon-like peptide 1 and 2 (aGLP-1 and GLP-2) using ELISA tests.
  • The effects of ID status and treatment on peptide concentrations were analyzed using t tests and analyses of variance.

Results

  • The study found that horses with ID had significantly higher maximum GIP concentrations than healthy horses.
  • However, there was no significant change in the concentrations of aGLP-1 and GLP-2 in relation with the ID status.
  • Phenylbutazone therapy showed a meaningful decrease in GIP in horses with ID as compared to the placebo treatment.
  • No significant effect of phenylbutazone was detected on aGLP-1 and GLP-2 concentrations.

Conclusion

  • The research concluded that a decrease in glucose and insulin concentrations after the administration of phenylbutazone was not mediated by GIP, aGLP-1 or GLP-2.
  • It was only GIP that was consistently linked with ID status, hinting towards the debatable role of the enteroinsular axis in insulin dysregulation.

Cite This Article

APA
Kemp KL, Skinner JE, Bertin FR. (2024). Effect of phenylbutazone administration on the enteroinsular axis in horses with insulin dysregulation. J Vet Intern Med, 39(1), e17256. https://doi.org/10.1111/jvim.17256

Publication

ISSN: 1939-1676
NlmUniqueID: 8708660
Country: United States
Language: English
Volume: 39
Issue: 1
Pages: e17256

Researcher Affiliations

Kemp, Kate L
  • School of Veterinary Science, The University of Queensland, 5391 Warrego Hwy, Gatton, Queensland, 4343, Australia.
Skinner, Jazmine E
  • School of Agriculture and Environmental Science, University of Southern Queensland, 487 - 35 West St, Darling Heights, Queensland, 4350, Australia.
Bertin, François-René
  • School of Veterinary Science, The University of Queensland, 5391 Warrego Hwy, Gatton, Queensland, 4343, Australia.
  • College of Veterinary Medicine, Department of Veterinary Clinical Sciences, Purdue University, 625 Harrison St, West-Lafayette, Indiana, 47909, USA.

MeSH Terms

  • Animals
  • Horses
  • Phenylbutazone / therapeutic use
  • Phenylbutazone / administration & dosage
  • Phenylbutazone / pharmacology
  • Horse Diseases / drug therapy
  • Cross-Over Studies
  • Insulin / blood
  • Male
  • Female
  • Glucose Tolerance Test / veterinary
  • Gastric Inhibitory Polypeptide / blood
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use
  • Anti-Inflammatory Agents, Non-Steroidal / administration & dosage
  • Glucagon-Like Peptide 1
  • Blood Glucose / drug effects

Grant Funding

  • D19-EQ-302 / Morris Animal Foundation
  • The University of Queensland Graduate School Research Training Program (RTP) Scholarship and Destination Australia Scholarship: Awarded to Kate L. Kemp

Conflict of Interest Statement

Authors declare no conflict of interest.

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