Distribution of insulin receptor and insulin-like growth factor-1 receptor in the digital laminae of mixed-breed ponies: an immunohistochemical study.
Authors: Burns T A, Watts M R, Weber P S, McCutcheon L J, Geor R J, Belknap J K
Journal: Equine veterinary journal
Summary
# Editorial Summary Hyperinsulinaemia is increasingly recognised as a key factor in laminitis development, yet which laminar cell populations actually respond to elevated insulin has remained unclear until now. Burns and colleagues used immunohistochemical staining to map insulin receptor (IRc) and insulin-like growth factor-1 receptor (IGF-1R) distribution across laminar tissues in 22 mixed-breed ponies stratified by body condition (lean or obese) and fed either low (6%) or high (42%) nonstructural carbohydrate diets for seven days. High dietary NSC significantly increased the number of IRc-positive cells in the laminae and this correlated strongly with serum insulin elevation (r² = 0.74); critically, IRc expression was confined to vascular endothelial cells rather than the epithelial cells that bear the mechanical load during laminitis, whilst IGF-1R showed broader distribution across endothelial, epithelial and fibroblast populations. These findings suggest that direct insulin signalling in laminar keratinocytes is unlikely, pointing instead to IGF-1R or indirect mechanisms as the primary pathways mediating epithelial response to hyperinsulinaemia. Understanding this cellular-level distinction opens avenues for targeted intervention strategies—modulating receptor signalling downstream of IGF-1R and IRc may offer novel approaches to preventing and treating hyperinsulinaemic laminitis, particularly in the growing population of metabolically compromised horses and ponies.
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Practical Takeaways
- •Dietary carbohydrate restriction reduces insulin receptor expression in digital laminae, providing mechanistic support for low-NSC feeding protocols in laminitis prevention and management
- •Laminar epithelial cells appear to respond to insulin primarily through IGF-1R rather than classical insulin receptors, suggesting therapeutic targeting of IGF-1R signaling pathways may benefit hyperinsulinaemic laminitis
- •Obese ponies on high-carbohydrate diets develop excessive laminar endothelial insulin receptor expression, supporting aggressive dietary management as a first-line laminitis prevention strategy in at-risk animals
Key Findings
- •Laminar insulin receptor (IRc) expression in endothelial cells increased significantly in ponies fed high NSC diet (42% NSC) compared to low NSC diet (6% NSC, P=0.001)
- •Strong positive correlation between serum insulin concentration change and number of IRc(+) cells (r²=0.74; P<0.0001)
- •Laminar keratinocytes do not express IRc, indicating insulin signaling in epithelial cells must occur through alternative receptors such as IGF-1R
- •IGF-1R expression was more widespread than IRc, found in vascular elements, epithelial cells and fibroblasts