Receptors for polypeptide hormones: Direct studies of insulin binding to purified liver plasma membranes

Summary This presentation is confined to a discussion of the binding of insulin to specific insulin receptors on isolated preparations of purified plasma membranes from rodent livers. The system has been studied extensively and has yielded a large amount of quantitative data. This study was a collaborative effort between my laboratory and the Section on Diabetes of the National Institute of Arthritis, Metabolic, and Digestive Diseases. The studies were begun by Pierre Freychet, Jesse Roth, and myself. The work on the obese mouse was initiated by Ronald Kahn and has been continued recently with Andrew Soll. When these experiments were begun, we hoped that, by using highly purified plasma membranes and a biologically active labeled hormone, ¹²⁵I]-monoiodoinsulin, we could accurately quantitative receptor binding isotherms, or receptor concentration and affinity, to such a degree that we could determine whether receptors were involved in the pathophysiology of insulin-resistant states. As the work progressed, and we realized that such quantitation was possible, we began to think of the insulin and insulin-receptor interaction as a general model for the interaction of a message from the external environment and a cell surface, which creates a change in cell behavior. Because the plasma membrane separates the external environment of a cell from the internal environment, there seemed to be good reason to believe that plasma membranes would be highly specialized for receiving many diverse types of messages. The most important finding of this work, if we may generalize from the insulin receptor, is that the specialization of the plasma membrane for receiving messages from the external environment involves control mechanisms which can alter the concentration of plasma membrane receptor. The response of a cell to an external message is therefore not uniquely determined by the concentration of the message, but also by the concentration of the receptor which, in the case of the insulin receptor, can be varied by metabolic and hormonal factors. Presented in the Symposium on Cell Membranes at the Twenty-fourth Annual Meeting of the Tissue Culture Association, June 1973.