Title page for ETD etd-07072010-090728

Type of Document Master's Thesis
Author Wearn, Jamie Macquarie
Author's Email Address jwearn@vt.edu
URN etd-07072010-090728
Title A pharmacokinetic and pharmacodynamic study of pioglitazone in a model of induced insulin resistance in normal horses
Degree Master of Science
Department Biomedical and Veterinary Sciences
Advisory Committee
Advisor Name Title
Crisman, Mark Virgil Committee Chair
Hodgson, David Committee Member
McCutcheon, L. Jill Committee Member
Pleasant, Robert Scott Committee Member
  • Pioglitazone
  • Insulin Resistance
  • Equine Metabolic Syndrome
  • Horse
  • Thiazolidinedione
Date of Defense 2010-05-28
Availability unrestricted
Equine Metabolic Syndrome (EMS) is a unique condition of horses characterized by adiposity, insulin resistance, and an increased risk of laminitis. Reducing insulin resistance may decrease the incidence of laminitis in horses with EMS. Pioglitazone, a thiazolidinedione class of anti-diabetic drug, has proven efficacy in humans with type 2 diabetes, a syndrome of insulin resistance sharing some similarities with EMS. The ability of pioglitazone to influence insulin sensitivity in an endotoxin-infusion model of induced insulin resistance was investigated. Our hypothesis was that piogltiazone would preserve insulin sensitivity in a model of induced insulin resistance. The specific aims were to investigate the pharmacokinetics and pharmacodynamics of pioglitazone in an endotoxin infusion model of insulin resistance.

16 normal adult horses were enrolled. Pioglitazone was administered to 8 horses (1 mg/kg, PO, q24h) for 14 days, and 8 horses served as their controls. Liquid chromatography with tandem mass spectroscopy was used to quantitate plasma concentration of pioglitazone. A frequently sampled intravenous glucose tolerance test with minimum model analysis was used to compare indices of glucose and insulin dynamics prior to, and following, endotoxin infusion in horses treated with pioglitazone and their controls. Parameters of clinical examination and lipid metabolism were compared prior to, and following, endotoxin administration.

Pioglitazone administered orally at 1 mg/kg q 24 h resulted in plasma concentrations lower, and more variable, compared to those considered therapeutic in humans. No significant effect of drug treatment was detected on clinical parameters or indices of insulin dynamics or lipid homeostasis following endotoxin challenge.

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