Proliferative Effects of Insulin on Equine Lamellar Epithelial Cells Mediated By the IGF-1 Receptor

Article Outline

• Take Home Message
• Introduction
• Materials & Methods
• Results
• Discussion
• Conclusion and Clinical Relevance
• Copyright

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Take Home Message 

High concentrations of insulin may have a direct effect on equine lamellar epithelial cells, mediated by the IGF-1 receptor.

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Introduction 

Hyperinsulinemia may be associated with increased risk of laminitis, and prolonged infusion of insulin can induce laminitis. It is unclear whether insulin may have a direct or indirect effect on the lamellar tissues. Insulin is structurally related to insulin-like growth factor (IGF-1), and can bind the IGF-1 receptor, albeit at lower affinity than IGF-1.

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Materials & Methods 

Immunohistochemistry was performed on formalin-fixed lamellar tissue sections from 6 normal horses using an anti-IGF-1 receptor antibody. Lamellar epithelial cells were obtained by collagenase digestion, and incubated for 3 days in the presence of insulin (0-1000 mIU/ml). The change in cell numbers was determined using an MTT cell proliferation assay, and compared to the effect of zero insulin using 1-way ANOVA.

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Results 

Immunohistochemistry demonstrated IGF-1 receptors on lamellar epidermal epithelial cells. With cultured cells, insulin caused a concentration-dependent increase in cell proliferation compared to untreated cells (53.8 ± 12.0 % more cells with 500 μIU/ml insulin; p < 0.01). Co-incubation with a blocking antibody against the IGF-1 receptor (1:50 dilution) significantly inhibited the proliferative effect of insulin (p < 0.01).

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Discussion 

These results demonstrate that IGF-1 receptors are present on lamellar epithelial cells. At high concentrations, insulin may activate these receptors to cause a proliferative effect.

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Conclusion and Clinical Relevance 

High concentrations of insulin may have a direct effect on equine lamellar epithelial cells, mediated by the IGF receptor. This mechanism could help to explain the link between hyperinsulinemia and laminitis.