Insulin resistance in equine digital vessel rings: an in vitro model to study vascular dysfunction in equine laminitis.
Authors: Venugopal, Eades, Holmes, Beadle
Journal: Equine veterinary journal
Summary
# Editorial Summary Hyperinsulinaemia is increasingly recognised as a significant risk factor for equine laminitis, with emerging evidence suggesting that insulin resistance and endothelial dysfunction in digital vessels contribute to this devastating condition. Venugopal and colleagues developed an in vitro model using palmar digital vessel rings harvested from healthy horses, exposing them to insulin and various signalling pathway inhibitors to replicate the vascular insulin resistance thought to occur in laminitis-affected animals. The researchers found that whilst insulin normally causes vasodilation in untreated vessel rings, those pretreated with insulin or wortmannin (a phosphatidylinositol 3-kinase inhibitor) paradoxically contracted in response to insulin, demonstrating successful induction of insulin resistance in both arterial and venous segments. The study also indicated that the mitogen-activated protein kinase pathway plays only a minor role in normal vascular tone regulation, suggesting the phosphatidylinositol 3-kinase pathway is the primary mechanism controlling insulin-mediated vasodilation. This reliable in vitro model offers a valuable research tool for equine professionals seeking to better understand the vascular mechanisms underpinning hyperinsulinaemia-associated laminitis, potentially paving the way for targeted therapeutic interventions in insulin-dysregulating conditions such as equine metabolic syndrome and pituitary pars intermedia dysfunction.
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Practical Takeaways
- •This in vitro model provides a reliable laboratory tool for investigating vascular dysfunction mechanisms in hyperinsulinaemic laminitis, potentially leading to better therapeutic targets.
- •Understanding that insulin resistance causes abnormal vascular contraction rather than relaxation may explain reduced blood flow to laminae in insulin-associated laminitis cases.
- •The PI3-kinase pathway's central role suggests potential future therapeutic interventions could target this pathway to restore normal vascular insulin sensitivity in laminitis-prone horses.
Key Findings
- •Insulin resistance was successfully induced in both arterial and venous palmar digital vessel rings through 30-minute exposure to insulin in vitro.
- •Insulin-resistant vessel rings showed reversed vasomotor response, converting normal relaxation to contraction when exposed to insulin.
- •The MAP-kinase signalling pathway plays a minor role in controlling normal vasomotor tone, as blocking it did not prevent normal insulin relaxation.
- •Wortmannin pretreatment (blocking PI3-kinase) successfully induced insulin resistance, indicating this pathway is critical for normal insulin-mediated vasodilation.