PhD Candidate The University of Queensland Gatton, Queensland, Australia
Abstract:
Background: Phenylbutazone is prescribed for the management of hyperinsulinemia-associated laminitis; however, non-steroidal anti-inflammatory drugs are used in diabetic people to stimulate pancreatic activity and insulin secretion. We have demonstrated that phenylbutazone decreased glucose concentration in horses with insulin dysregulation (ID); however, it did not appear directly regulated by insulin secretion.
Hypothesis/
Objectives: Phenylbutazone alters pancreatic activity through the entero-insular axis in horses with ID.
Animals: Nineteen University-owned horses including 10 with ID.
Methods: In a randomised crossover trial, horses received intravenous phenylbutazone (4.4 mg/kg daily) or placebo, with a 10-day washout period between treatments. On day 9 of treatment, an oral glucose test (OGT) was performed. Insulin concentrations were measured with the IMMULITE1000, glucose with a handheld glucometer and gastric inhibitory polypeptide (GIP) with a previously validated ELISA. Changes in insulin, glucose and GIP concentrations, as well as glucose-induced secretions of insulin and GIP were analyzed with linear mixed effect models and paired tests with P < .05 considered significant.
Results: In horses with ID, phenylbutazone administration decreased post-OGT glucose concentrations with both lower areas under the curve (P = .0031) and lower maximum glucose concentrations (P = .0062). Although, post-OGT insulin concentrations were not altered by phenylbutazone administration (P = .7903), a higher glucose-induced insulin secretion was detected (P = .0466) which was associated with an increased glucose-induced GIP secretion (P = .0200). No phenylbutazone-induced changes were detected in control horses.
Conclusion and clinical importance: In horses with ID, phenylbutazone induces a higher pancreatic activity mediated by the entero-insulin axis.
