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Effects of an intravenous endotoxin challenge on glucose and insulin dynamics in horses

Ferenc TóthDepartment of Large Animal Clinical Sciences, College of Veterinary Medicine, University of Tennessee, Knoxville, TN 37996.

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Nicholas FrankDepartment of Large Animal Clinical Sciences, College of Veterinary Medicine, University of Tennessee, Knoxville, TN 37996.

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Sarah B. ElliottDepartment of Large Animal Clinical Sciences, College of Veterinary Medicine, University of Tennessee, Knoxville, TN 37996.

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Raymond J. GeorMiddleburg Agricultural Research and Extension Center, Virginia Polytechnic and State University, Middleburg, VA 20117.

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Raymond C. BostonDepartment of Clinical Studies, School of Veterinary Medicine, University of Pennsylvania, Kennett Square, PA 19348.

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Abstract

Objective—To evaluate the effects of endotoxin administered IV on glucose and insulin dynamics in horses.

Animals—16 healthy adult mares.

Procedures—Each week of a 2-week randomized crossover study, each horse received an IV injection (duration, 30 minutes) of Escherichia coli O55:B5 lipopolysaccharide (LPS) in 60 mL of sterile saline (0.9% NaCl) solution (20 ng/kg) or sterile saline solution alone (control treatment). Frequently sampled IV glucose tolerance test procedures were performed at 24 hours before (baseline) and 24 and 48 hours after injection; glucose and insulin dynamics were assessed via minimal model analysis.

Results—13 of 16 horses had a clinical response to LPS, which was characterized by mild colic and leukopenia. Before treatment, mean ± SD insulin sensitivity was 2.9 ± 1.9 × 10−4 L·min−1·mU−1; this significantly decreased to 0.9 ± 0.9 × 10−4 L·min−1·mU−1 24 hours after treatment (69% reduction) and was 1.5 ± 0.9 × 10−4 L·min−1·mU−1 48 hours after treatment. At baseline, mean ± SD acute insulin response to glucose was 520 ± 196 mU·min·L−1; this significantly increased to 938 ± 620 mU·min·L−1 (80% increase) and 755 ± 400 mU·min·L−1 (45% increase) at 24 and 48 hours after LPS treatment, respectively.

Conclusions and Clinical Relevance—Compared with baseline values, insulin sensitivity was decreased for 24 hours after IV injection of LPS, and affected horses had a compensatory pancreatic response. These disturbances in glucose and insulin dynamics may contribute to development of laminitis in horses.

Abstract

Objective—To evaluate the effects of endotoxin administered IV on glucose and insulin dynamics in horses.

Animals—16 healthy adult mares.

Procedures—Each week of a 2-week randomized crossover study, each horse received an IV injection (duration, 30 minutes) of Escherichia coli O55:B5 lipopolysaccharide (LPS) in 60 mL of sterile saline (0.9% NaCl) solution (20 ng/kg) or sterile saline solution alone (control treatment). Frequently sampled IV glucose tolerance test procedures were performed at 24 hours before (baseline) and 24 and 48 hours after injection; glucose and insulin dynamics were assessed via minimal model analysis.

Results—13 of 16 horses had a clinical response to LPS, which was characterized by mild colic and leukopenia. Before treatment, mean ± SD insulin sensitivity was 2.9 ± 1.9 × 10−4 L·min−1·mU−1; this significantly decreased to 0.9 ± 0.9 × 10−4 L·min−1·mU−1 24 hours after treatment (69% reduction) and was 1.5 ± 0.9 × 10−4 L·min−1·mU−1 48 hours after treatment. At baseline, mean ± SD acute insulin response to glucose was 520 ± 196 mU·min·L−1; this significantly increased to 938 ± 620 mU·min·L−1 (80% increase) and 755 ± 400 mU·min·L−1 (45% increase) at 24 and 48 hours after LPS treatment, respectively.

Conclusions and Clinical Relevance—Compared with baseline values, insulin sensitivity was decreased for 24 hours after IV injection of LPS, and affected horses had a compensatory pancreatic response. These disturbances in glucose and insulin dynamics may contribute to development of laminitis in horses.

Contributor Notes

Supported by a grant from American Quarter Horse Foundation and the Charles and Julie Wharton Laminitis Fellowship.

Address correspondence to Dr. Frank.