High concentrations of insulin may have a direct effect on equine lamellar epithelial cells, mediated by the IGF-1 receptor.
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.
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.
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).
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.
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.
Faculty of Veterinary Science, University of Melbourne, Victoria 3010, Australia
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