Date of Award
Doctor of Philosophy
Comparative and Experimental Medicine
The present studies were performed to investigate the effects of endotoxemia on glucose and insulin dynamics, and to examine their relationship to laminitis in horses. The frequently sampled intravenous glucose tolerance test was evaluated and refined for use in horses. A new FSIGTT was developed, consisting of 100 mg/kg dextrose followed by 20 mU/kg insulin 20 min later. This new test was used in subsequent experiments to assess glucose and insulin dynamics while minimizing urine glucose spillover. Serum Cpeptide concentrations were measured in horses to investigate pancreatic function and this work revealed a decrease in C-peptide-to-insulin ratio after dextrose challenge, suggesting reduced hepatic insulin extraction. Administration of endotoxin both as an intravenous bolus and 8-hour continuous rate infusion significantly lowered insulin sensitivity and increased the acute insulin response to glucose.The effects of resting insulin sensitivity on the magnitude of insulin resistance induced by endotoxin administration were subsequently investigated. Resting insulin sensitivity was successfully reduced by oral administration of 20 mg dexamethasone, but levothyroxine sodium failed to improve insulin sensitivity. However, endotoxemia-induced insulin resistance was ameliorated by pretreatment with levothyroxine sodium. Administration of endotoxin alone, oligofructose alone, or endotoxin followed by oligofructose resulted in the development of Obel grade [greater than or equal to] 2 laminitis in 0/8, 1/8 and 5/8 horses, respectively, indicating a significant association between endotoxemia and laminitis. In summary, results show that endotoxemia exerts an adverse effect on glucose and insulin dynamics and plays an important role in the development of laminitis in horses.Pretreatment with levothyroxine sodium prevented insulin resistance associated with endotoxemia, so this treatment warrants further investigation.
Tóth, Ferenc, "Glucose and insulin dynamics in horses and their association with endotoxemia and laminitis. " PhD diss., University of Tennessee, 2009.