Effect of 5'-adenosine monophosphate-activated protein kinase agonists on insulin and glucose dynamics in experimentally induced insulin dysregulation in horses.
Authors: Pinnell Erin F, Hostnik Laura D, Watts Mauria R, Timko Kathryn J, Thriffiley Allison A, Stover Mercedes R, Koenig Lauren E, Gorman Olivia M, Toribio Ramiro E, Burns Teresa A
Journal: Journal of veterinary internal medicine
Summary
# Editorial Summary Insulin dysregulation in horses remains challenging to manage, and whilst AMPK agonists show metabolic promise in other species, their efficacy in equine insulin resistance has been poorly characterised. Researchers induced insulin dysregulation in 33 healthy horses using dexamethasone and then evaluated whether resveratrol (10 mg/kg twice daily), metformin (30 mg/kg twice daily), aspirin (20 mg/kg once daily), or various combinations could reverse the metabolic dysfunction using frequently sampled intravenous glucose tolerance tests and oral sugar tests. Despite dexamethasone successfully impairing insulin sensitivity and glucose dynamics—and triggering clinical laminitis in 15% of horses—none of the single agents or combination treatments significantly improved these parameters over the seven-day treatment period. For practitioners, these findings suggest that current pharmacological approaches may have limited effect on acute insulin dysregulation, highlighting the importance of metabolic screening before glucocorticoid administration in horses showing metabolic syndrome traits, and potentially pointing toward the need for longer treatment duration, alternative compounds, or multimodal management strategies beyond pharmacotherapy alone.
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Practical Takeaways
- •AMPK agonist therapy with resveratrol, metformin, or aspirin should not be relied upon as effective treatments for insulin dysregulation in horses—consider alternative therapeutic approaches
- •Horses receiving glucocorticoids require baseline metabolic testing to identify insulin dysregulation early, as 14 days of dexamethasone significantly impaired glucose regulation and caused clinical laminitis in some animals
- •The combination of three different AMPK agonists failed where individual agents might have been expected to work; current evidence does not support their use for managing metabolic syndrome in horses
Key Findings
- •Dexamethasone administration for 14 days significantly altered insulin and glucose dynamics (SI, DI, basal glucose and insulin levels) and induced clinical laminitis in 15% (5/33) of horses
- •Combination therapy with resveratrol, metformin, and aspirin did not significantly improve insulin and glucose dynamics in horses with experimentally induced insulin dysregulation
- •AMPK agonists including resveratrol, metformin, and aspirin were ineffective at reversing experimentally induced metabolic dysfunction in horses