Effects of Pretreatment with Dexamethasone or Levothyroxine Sodium on Endotoxin-Induced Insulin Resistance in Horses
Endotoxemia has been associated with laminitis, and transient insulin resistance (IR) develops after administration of exogenous lipopolysaccharide (LPS) to horses. We hypothesized that resting insulin sensitivity would affect the magnitude of IR induced by LPS. Horses were pretreated with dexamethasone (20 mg/day PO) to induce IR or levothyroxine sodium (LT4; 48 mg/day PO) to increase insulin sensitivity. Twenty adult mares were randomly assigned to control (no pretreatment; n = 8), dexamethasone (n = 4), and LT4 (n = 8) groups. After the 14-day pretreatment period, horses were challenged by intravenous administration of 20 ng/kg body weight Escherichia coli O55:B5 LPS. Frequently-sampled intravenous glucose tolerance test procedures were performed at -14 days, -3 h, and 20 h relative to LPS administration. Areas under the plasma glucose (AUCg) and serum insulin (AUCi) curves were calculated.
Significant treatment × time effects were detected for AUCg (P = 0.018) and AUCi (P < 0.001) for the 14-day pretreatment period. Treatment with dexamethasone for 14 days significantly (P < 0.001) increased pre-LPS mean AUCg and mean AUCi values by 24% and 364%, respectively, suggesting a significant decrease in insulin sensitivity over time. Furthermore, pretreatment with dexamethasone exacerbated IR induced by LPS. Mean AUCg and AUCi values did not change significantly over 14 days in the LT4 group and this drug prevented LPS-induced IR. Results suggest that horses already suffering from IR are likely to show greater disturbances in insulin sensitivity when endotoxemia develops, and LT4 pretreatment ameliorates these responses to LPS.