Insulin-receptor interactions. Possible involvement of metals.

Addition of Zn2+ or Cu2+ ions to plasma membrane preparations or to purified insulin receptors from rat liver resulted in an increase of specific insulin binding; no effect was observed with the addition of Fe3+, Ca2+ or Na+. Dialysis of membrane preparations, or of purified receptors, against chelating agents such as zincon (2-carboxy-2'-hydroxy-5'-sulfoformazyl-benzene) or 1,10-phenantroline resulted in a decrease in specific binding of insulin. With the readdition of Zn2+ or Cu2+ to the medium an increase in specific binding was observed, and values much higher than those of the original preparations were obtained; the addition of Ca2+, Fe3+ or Na+ to dialyzed preparations did not cause any effect on the specific binding. Dialysis of purified receptors against chelating agents resulted in a decrease in the content of Zn2+ and Cu2+. Zincon has been found to be a competitive inhibitor of insulin interfering with the specific binding to the receptor, and noncompetitive with the nonspecific binding. These results suggest the possible involvement of a metal ion present in the receptor in the formation of the insulin-receptor complex.