The effect of insulin on equine lamellar basal epithelial cells mediated by the insulin-like growth factor-1 receptor

BACKGROUND: In horses and ponies, insulin dysregulation leading to hyperinsulinemia may be associated with increased risk of laminitis, and prolonged infusion of insulin can induce the condition. 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 a lower affinity than IGF-1. METHODS: Immunohistochemistry was performed on formalin-fixed lamellar tissue sections from six normal horses, euthanised for non-research purposes, using an anti-IGF-1 receptor antibody. In further studies, lamellar epithelial cells were obtained by collagenase digestion from the hooves of 18 normal horses, also euthanised for non-research purposes, and incubated for 48 h in the presence of insulin (0–2,000 m IU/ml). The increase in cell numbers was determined using a cell proliferation assay, and compared to the effect of zero insulin using one-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 (maximal effect 63.3 ± 12.8% more cells after 48 h with 1,000 m IU/ml insulin; P < 0.01). Co-incubation with a blocking antibody against the IGF-1 receptor 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 physiological concentrations, insulin may activate these cells, by a mechanism involving IGF-1 receptors, resulting in a proliferative effect. This mechanism could help to explain the link between hyperinsulinemia and laminitis.