Effects of pretreatment with dexamethasone or levothyroxine sodium on endotoxin-induced alterations in glucose and insulin dynamics in horses.
Abstract: To investigate the effects of dexamethasone or levothyroxine sodium on endotoxin-induced alterations in glucose and insulin dynamics. Methods: 24 horses. Methods: Horses were randomly allocated to 3 treatment groups and received 48 mg of levothyroxine mixed with 200 g of oats, 20 mg of dexamethasone plus oats, or oats alone (control) for 15 days, followed by IV infusion of lipopolysaccharide (20 ng/kg) while individually housed in stalls. Frequently sampled IV glucose tolerance tests were performed prior to pretreatment, after pretreatment, and 20 hours after lipopolysaccharide administration. Area under the curve for plasma glucose and serum insulin concentrations was calculated, and minimal model analyses were performed. Results: Significant treatment-by-time effects were detected for insulin sensitivity (SI) and area under the curve for glucose and insulin in the 15-day pretreatment period. Insulin sensitivity significantly decreased over time in all treatment groups, with the largest decrease detected in the dexamethasone group. Administration of lipopolysaccharide further decreased mean SI by 71% and 63% in the dexamethasone and control groups, respectively, but did not affect horses in the levothyroxine group. Mean SI was the lowest in the dexamethasone group, but percentage reduction was the same for dexamethasone and control groups. Conclusions: Insulin sensitivity decreased during the pretreatment period in all 3 groups, indicating that hospitalization affected glucose and insulin dynamics. Dexamethasone significantly lowered SI, and endotoxemia further exacerbated insulin resistance. In contrast, there was no additional effect of endotoxemia on SI in horses pretreated with levothyroxine, suggesting that this treatment prevented endotoxemia-induced insulin resistance.
Publication Date: 2010-01-02 PubMed ID: 20043782DOI: 10.2460/ajvr.71.1.60Google Scholar: Lookup
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- Journal Article
- Randomized Controlled Trial
- Research Support
- Non-U.S. Gov't
Summary
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The study aims to understand the impact of two different drugs, dexamethasone and levothyroxine sodium, on disruptions in glucose and insulin responses caused by endotoxins in horses. The researchers found that while both dexamethasone and hospitalization lowered insulin sensitivity, levothyroxine sodium seemed to prevent this reaction in response to endotoxin exposure.
Methodology
- Twenty-four horses were subjected to the study and were randomly assigned into three groups.
- One group was given 48 mg of levothyroxine mixed with 200 g of oats, another group received 20 mg of dexamethasone with oats, and the third (control) group was given oats alone.
- The treatment lasted for 15 days, after which, the horses were given an IV infusion of lipopolysaccharide, an endotoxin, at a dose of 20 ng/kg.
- Frequent IV glucose tolerance tests were conducted before the treatment, after treatment, and 20 hours following the endotoxin administration.
- The scientists also measured the area under the curve (AUC) for the plasma glucose and serum insulin concentrations and performed minimal model analyses.
Results
- The results demonstrated significant treatment-by-time effects on insulin sensitivity and glucose and insulin AUC.
- Insulin sensitivity decreased over time in all treatment groups, with the largest drop noticed in the dexamethasone group.
- The infusion of endotoxin reduced mean insulin sensitivity by 71% and 63% in the dexamethasone and control groups, respectively, but did not affect horses in the levothyroxine group.
- The lowest mean insulin sensitivity was noted in the dexamethasone group, however, the percentage reduction was the same in both dexamethasone and control groups.
Conclusions
- In all three groups, insulin sensitivity decreased during the pretreatment period, indicating that the hospitalization process itself interfered with glucose and insulin dynamics.
- The dexamethasone treatment notably diminished insulin sensitivity, and the condition of endotoxemia further intensified this insulin resistance.
- Contrary to dexamethasone, levothyroxine proved to prevent the endotoxin-induced drop in insulin sensitivity. Therefore it can potentially be used as a treatment against endotoxemia-related insulin resistance in horses.
Cite This Article
APA
Tóth F, Frank N, Geor RJ, Boston RC.
(2010).
Effects of pretreatment with dexamethasone or levothyroxine sodium on endotoxin-induced alterations in glucose and insulin dynamics in horses.
Am J Vet Res, 71(1), 60-68.
https://doi.org/10.2460/ajvr.71.1.60 Publication
Researcher Affiliations
- Department of Large Animal Clinical Sciences, College of Veterinary Medicine, University of Tennessee, Knoxville, TN 37996, USA.
MeSH Terms
- Animals
- Blood Glucose / drug effects
- Dexamethasone / administration & dosage
- Dexamethasone / pharmacology
- Female
- Glucocorticoids / administration & dosage
- Glucocorticoids / pharmacology
- Horses
- Insulin / metabolism
- Insulin Resistance
- Lipopolysaccharides / toxicity
- Thyroxine / administration & dosage
- Thyroxine / pharmacology
Citations
This article has been cited 3 times.- Mendoza Garcia FJ, Gonzalez-De Cara C, Aguilera-Aguilera R, Buzon-Cuevas A, Perez-Ecija A. Meloxicam ameliorates the systemic inflammatory response syndrome associated with experimentally induced endotoxemia in adult donkeys.. J Vet Intern Med 2020 Jul;34(4):1631-1641.
- Frank N, Walsh DM. Repeatability of Oral Sugar Test Results, Glucagon-Like Peptide-1 Measurements, and Serum High-Molecular-Weight Adiponectin Concentrations in Horses.. J Vet Intern Med 2017 Jul;31(4):1178-1187.
- Hart KA, Wochele DM, Norton NA, McFarlane D, Wooldridge AA, Frank N. Effect of Age, Season, Body Condition, and Endocrine Status on Serum Free Cortisol Fraction and Insulin Concentration in Horses.. J Vet Intern Med 2016 Mar-Apr;30(2):653-63.
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