Insulin-receptor interactions in liver cell membranes

Abstract

The specific binding of 125I-insulin to liver cell membranes is a saturable process with respect to insulin. Binding is displaced by low concentrations of native insulin but not by biologically inactive insulin derivatives or by other peptide hormones. The rate constants of association (3.5 × 10 6 mole −1 sec −1) and of dissociation (2.7 × 10 −4 sec −1) of the insulin-membrane complex can be determined independently. The dissociation constant of the complex, determined from the rate constants and from equilibrium data, is about 7 × 10 −11M. Complex formation does not result in degradation of the insulin molecule. The binding interaction is a dissociable process involving a homogeneous membrane structure which is almost certainly the biologically significant receptor. The kinetic properties, and the effects of enzymic perturbations of the membrane, suggest that the insulin receptors of liver and of adipose tissue cells may be very similar structures.