Control of insulin receptor affinity by a Ca2+-sensitive binding site

Calcium (Ca²⁺) increased insulin-receptor binding in both membrane and solubilised receptor preparations. Ca²⁺ increased both receptor affinity and initial rate of association of [¹²⁵I]insulin to the receptor preparations. Ca²⁺ had no effect on insulin receptor number in either receptor preparation. The effect of Ca²⁺ on affinity could be mimicked by ions with similar ionic radii and properties (e.g., Ba²⁺, Mg²⁺ and Sr²⁺). EDTA and oleic acid reduced insulin binding and receptor affinity and these effects were reversed by the addition of Ca²⁺. These studies suggest that Ca²⁺ and Ca²⁺-like ions may bind to a site on or near the receptor and may be responsible for a conformational change with a consequent increase in receptor affinity.