Formation of a receptor state from which insulin dissociates slowly in hepatic cells and plasma membranes.

125I-insulin dissociated from rat hepatocytes and liver plasma membranes with a time course suggestive of more than a single kinetic process. Dissociation curves were resolved into rapidly and slowly dissociating components. Increasing times of hormone-cell or hormone-membrane incubation prior to the initiation of dissociation increased the proportion of slowly dissociable 125I-insulin and decreased the proportion of rapidly dissociating hormone. The rates of loss of rapidly and slowly dissociating 125I-insulin, 1 to 2 x 10(-3) and 2 to 7 x 10(-5) s-1, respectively, were the same in cell and membrane incubates. The capacity of liver membranes and hepatocytes to bind 125I-insulin in a slowly dissociable state was saturable with respect to insulin concentration (approximately 10(-8) M). The observation of the same physical process in both cells and plasma membranes demonstrates a distinct role for receptors at the exterior surface of target cells in the retention of insulin.