Effect of 5′-adenosine monophosphate-activated protein kinase agonists on insulin and glucose dynamics in experimentally induced insulin dysregulation in horses.
Abstract: 5'-adenosine monophosphate-activated protein kinase (AMPK) agonists, particularly resveratrol (RES), have not been extensively evaluated for their effect on insulin dysregulation (ID) in horses. Objective: Evaluate the effects of treatment with RES (10 mg/kg PO q12h), metformin (MET; 30 mg/kg PO q12h), and aspirin (ASP; 20 mg/kg PO q24h) on experimentally induced ID. Methods: Thirty-three healthy, adult, light-breed horses. Methods: Unblinded, placebo-controlled, experimental trial evaluating effects of AMPK agonists (RES, MET, and ASP) on experimentally induced ID. Horses were randomly assigned to a treatment group (RES, MET/ASP, RES/ASP, RES/MET/ASP, or placebo [CON]) after induction of ID with dexamethasone (0.08 mg/kg PO q24h for 7 days). Frequently sampled insulin-modified IV glucose tolerance tests (FSIGTT) and oral sugar tests (OST) were performed at baseline, 7 days after ID, and ID plus 7 days of treatment. Minimal model and OST variables were compared between (1-way ANOVA) and within (1-way ANOVA for repeated measures) groups over time to determine effects of treatment on ID. Results: Administration of dexamethasone for 14 days resulted in significantly altered insulin and glucose dynamics (SI, DI, basal [glucose], and [insulin]) and produced clinical signs of laminitis in 5 out of 33 (15%) of horses included in the study. Combination therapy with RES, MET, and ASP did not significantly improve insulin and glucose dynamics in horses with experimentally induced ID. Conclusions: Metabolic testing before glucocorticoid administration should be considered in horses with clinical signs of metabolic syndrome.
© 2023 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.
Publication Date: 2023-12-13 PubMed ID: 38088223PubMed Central: PMC10800176DOI: 10.1111/jvim.16970Google Scholar: Lookup
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- Randomized Controlled Trial
- Veterinary
- Journal Article
Summary
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This study investigates the effects of various protein kinase agonists on insulin and glucose dynamics in horses with experimentally induced insulin dysregulation. The researchers found that combination therapy of these agonists did not significantly improve these dynamics in the studied horses.
Introduction and Objective
- The research focuses on the impact of 5′-adenosine monophosphate-activated protein kinase (AMPK) agonists on insulin dysregulation (ID) in horses. ID is associated with the potential development of laminitis, a severe foot condition in horses.
- The study particularly evaluates the treatment effects of resveratrol (RES), metformin (MET), and aspirin (ASP).
Methods
- Treatment groups were randomly assigned to the healthy adult light-breed horses after ID induction with dexamethasone. The groups included RES, MET/ASP, RES/ASP, RES/MET/ASP, and placebo.
- Both frequently sampled insulin-modified IV glucose tolerance tests (FSIGTT) and oral sugar tests (OST) were utilized before and after ID induction, as well as after the treatment period of 7 days.
- The study compares the minimal model and OST variables over time within and between the groups to judge the impact of the treatments on insulin dysregulation.
Results
- The induction of ID with dexamethasone over 14 days significantly altered insulin and glucose dynamics and produced laminitis symptoms in 15% of the horses.
- The combination treatment of RES, MET, and ASP did not notably improve the insulin and glucose dynamics.
Conclusions
- Essentially, the study suggests the potential risk of ID and laminitis due to glucocorticoid administration in horses exhibiting metabolic syndrome symptomatology.
- Therefore, metabolic testing is recommended prior to glucocorticoid administration in horses presenting metabolic syndrome clinical signs.
Cite This Article
APA
Pinnell EF, Hostnik LD, Watts MR, Timko KJ, Thriffiley AA, Stover MR, Koenig LE, Gorman OM, Toribio RE, Burns TA.
(2023).
Effect of 5′-adenosine monophosphate-activated protein kinase agonists on insulin and glucose dynamics in experimentally induced insulin dysregulation in horses.
J Vet Intern Med, 38(1), 102-110.
https://doi.org/10.1111/jvim.16970 Publication
Researcher Affiliations
- Department of Veterinary Clinical Sciences, The Ohio State University College of Veterinary Medicine, Columbus, Ohio, USA.
- Department of Veterinary Clinical Sciences, Washington State University College of Veterinary Medicine, Pullman, Washington, USA.
- Department of Veterinary Clinical Sciences, The Ohio State University College of Veterinary Medicine, Columbus, Ohio, USA.
- Department of Veterinary Clinical Sciences, The Ohio State University College of Veterinary Medicine, Columbus, Ohio, USA.
- Department of Veterinary Clinical Sciences, The Ohio State University College of Veterinary Medicine, Columbus, Ohio, USA.
- Department of Veterinary Clinical Sciences, The Ohio State University College of Veterinary Medicine, Columbus, Ohio, USA.
- Department of Veterinary Clinical Sciences, The Ohio State University College of Veterinary Medicine, Columbus, Ohio, USA.
- Department of Veterinary Clinical Sciences, The Ohio State University College of Veterinary Medicine, Columbus, Ohio, USA.
- Department of Veterinary Clinical Sciences, The Ohio State University College of Veterinary Medicine, Columbus, Ohio, USA.
- Department of Veterinary Clinical Sciences, The Ohio State University College of Veterinary Medicine, Columbus, Ohio, USA.
- Department of Veterinary Clinical Sciences, The Ohio State University College of Veterinary Medicine, Columbus, Ohio, USA.
MeSH Terms
- Horses
- Animals
- Glucose / metabolism
- Insulin / metabolism
- Blood Glucose
- Glucose Tolerance Test / veterinary
- AMP-Activated Protein Kinases
- Dexamethasone / pharmacology
- Dexamethasone / therapeutic use
- Adenosine Monophosphate
- Horse Diseases / diagnosis
Grant Funding
- Grayson Jockey Club Research Foundation
Conflict of Interest Statement
Authors declare no conflict of interest.
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