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BMC veterinary research2022; 18(1); 294; doi: 10.1186/s12917-022-03394-2

Effect of a GLP-1 mimetic on the insulin response to oral sugar testing in horses.

Abstract: Insulin dysregulation (ID) is the most important risk factor for the development of laminitis in horses and therapies to control it are needed. Objective: To assess the effects of a single dose of the synthetic GLP-1 analog exenatide on postprandial insulin dynamics. We hypothesized that exenatide would improve insulin sensitivity and lower postprandial blood insulin concentrations. Methods: Randomized, crossover, experimental study. Methods: Six horses (3 mares, 3 geldings; 2 with normal insulin regulation [NIR] and 4 with mild ID). Methods: Horses completed both study arms: subcutaneous administration of exenatide (or no treatment) 30 min before an oral sugar test (0.15 ml/kg of Karo Syrup). Blood samples obtained over 240 min were assayed for glucose, insulin, lactate, c-peptide and total GLP-1. The area under the curve (AUC) was calculated using the trapezoidal rule. Insulin sensitivity (S) was estimated using a mathematical model. Results: Exenatide resulted in a postprandial decrease of 20% (effect size: 2673 µU·min/ml; 95% CI: 900 - 4446 µU·min/ml; P = 0.003) in AUC of plasma insulin (control; mean AUC insulin: 11,989 µU·min/ml; 95% CI: 9673 - 14,305 µU·min/ml, exenatide; mean AUC insulin: 9316 µU·min/ml; 95% CI: 7430 - 11,202 µU·min/ml). Exenatide resulted in an approximately threefold increase (effect size: 5.56 10· µU/ml·min; 95% CI: 0.95 - 10.1 10· µU/ml·min; P = 0.02) in estimated insulin sensitivity (control mean S: 1.93 10· µU/ml·min; 95% CI: 0.005 - 3.86 10·µU/ml·min vs. exenatide mean S: 7.49 10· µU/ml·min; 95% CI: 3.46 - 11.52 10· µU/ml·min). Conclusions: The decrease in insulin response to carbohydrates was due to an increase in whole-body insulin sensitivity. GLP-1 agonists may have therapeutic potential for ID in horses.
© 2022. The Author(s).
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Publication Date: 2022-07-29 PubMed ID: 35906619PubMed Central: PMC9336084DOI: 10.1186/s12917-022-03394-2Google Scholar: Lookup
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  • Journal Article
  • Randomized Controlled Trial
  • Veterinary

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

This research article examines the effects of a synthetic GLP-1 analog, exenatide, on insulin regulation in horses, particularly with its potential to enhance insulin sensitivity and lower blood insulin concentrations post eating, hence suggesting its potential use as a therapeutic intervention for insulin dysregulation in horses.

Research Objectives and Hypothesis

  • The primary objective of the research was to assess the influence of a single dose of exenatide, a synthetic GLP-1 analog, on postprandial insulin dynamics in horses.
  • The researchers hypothesised that administration of exenatide would enhance insulin sensitivity and cause a decrease in postprandial blood insulin concentrations in horses.

Methods and Procedures

  • The investigation was undertaken as a randomized, crossover, experimental study involving six horses (3 mares, 3 geldings).
  • The horses, of which two had normal insulin regulation (NIR) and four had mild insulin dysregulation (ID), were subjected to both study arms – subcutaneous application of exenatide (or no treatment) thirty minutes prior to an oral sugar test.
  • The sugar test involved administering 0.15 ml/kg of Karo Syrup and subsequently obtaining blood samples over a period of 240 minutes.
  • The blood samples were tested for glucose, insulin, lactate, c-peptide, and total GLP-1 levels, and the area under the curve (AUC) for these values were calculated using the trapezoidal rule.
  • Insulin sensitivity was then estimated using a mathematical model.

Results

  • The use of exenatide resulted in a 20% decrease in the postprandial AUC of plasma insulin, confirming the lowered blood insulin concentration post eating.
  • Interestingly, the administered exenatide resulted in an approximately threefold increase in estimated insulin sensitivity, validating the hypothesis of the study.

Conclusion

  • The decrease in carbohydrate-induced insulin response was found to be due to an increase in whole-body insulin sensitivity due to exenatide administration.
  • The findings of the research suggests the potential of GLP-1 agonists, such as the tested exenatide, as therapeutic solutions for managing ID in horses.

Cite This Article

APA
Stefanovski D, Robinson MA, Van Eps A. (2022). Effect of a GLP-1 mimetic on the insulin response to oral sugar testing in horses. BMC Vet Res, 18(1), 294. https://doi.org/10.1186/s12917-022-03394-2

Publication

BMC veterinary research
ISSN: 1746-6148
NlmUniqueID: 101249759
Country: England
Language: English
Volume: 18
Issue: 1
Pages: 294
PII: 294

Researcher Affiliations

Stefanovski, Darko
  • Department of Clinical Studies, School of Veterinary Medicine, University of Pennsylvania, New Bolton Center Campus, 382 West Street Road, Kennett Square, PA, 19348, USA. sdarko@upenn.edu.
Robinson, Mary A
  • Department of Clinical Studies, School of Veterinary Medicine, University of Pennsylvania, New Bolton Center Campus, 382 West Street Road, Kennett Square, PA, 19348, USA.
  • PA Equine Toxicology & Research Laboratory, 220 East Rosedale Avenue, West Chester, PA, 19382, USA.
Van Eps, Andrew
  • Department of Clinical Studies, School of Veterinary Medicine, University of Pennsylvania, New Bolton Center Campus, 382 West Street Road, Kennett Square, PA, 19348, USA.

MeSH Terms

  • Animals
  • Blood Glucose
  • Exenatide
  • Female
  • Glucagon-Like Peptide 1
  • Horse Diseases
  • Horses
  • Insulin
  • Insulin Resistance
  • Male
  • Sugars

Grant Funding

  • PENUSDADSFo0 / U.S. Department of Agriculture
  • PENUSDADSFo0 / U.S. Department of Agriculture

Conflict of Interest Statement

The authors declare no competing interests. The authors have no competing interests to report. All experimental protocols have been approved by Institutional Animal Care and Use Committee.

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Citations

This article has been cited 1 times.
  1. de Laat MA, Fitzgerald DM, Harris PA, Bailey SR. A glucagon-like peptide-1 receptor antagonist reduces the insulin response to a glycemic meal in ponies. J Anim Sci 2023 Jan 3;101.
    doi: 10.1093/jas/skad389pubmed: 38066683google scholar: lookup
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