Changes of conformation and aggregation state induced by binding of lanthanide ions to insulin

To clarify the mechanism of lanthanide ions (Ln(3+)) on the across-membrane transport of insulin and subsequent reducing blood glucose, the interactions of Ln(3+) with Zn-insulin and Zn-free insulin are investigated by spectroscopic methods. The results reveal that the binding of Ln(3+) to insulin can induce its structure changes from secondary to quaternary structure, depending on the Ln(3+) concentration. In the lower concentration, it triggers the conformational changes of insulin monomer in the binding region with insulin receptor (B(24-30)). It would affect insulin-insulin receptor interaction. Moreover, Ln(3+) binding promotes the assembly of insulin monomer from dimer to polymer. The potency of Ln(3+) in inducing insulin's aggregation is stronger than that of Zn2+. Furthermore, the aggregation can be reversed partly by EDTA-treatment, indicating that it is not due to denaturation. Similar to Zn2+ effect, Ln(3+) can stabilize insulin hexamer in a certain range of concentration, but is stronger than the former.Chemistry, MultidisciplinarySCI(E)EI0ARTICLE4349-3574