We previously reported evidence for two classes of insulin receptors on erythrocytes based on the interaction with concanavalin A (Nature 28:279, 1980). Further evidence for this hypothesis is provided here when proinsulin is used as a competitive inhibitor of insulin binding to human and rabbit erythrocytes. Proinsulin in a molar ratio of 33:1 to insulin (Endocr. 107:195, 1980) binds to the low affinity, high capacity site in a preferential manner allowing the high affinity, low capacity site to be expressed. When insulin binding data are analyzed using a computer model (Ligand, NIH) the values obtained for affinity (K1) and maximum (R1) are nearly identified for site I as shown for a typical experiment.
We conclude that these findings are further evidence supporting the concept of two classes of insulin receptors on erythrocytes. If only the linear site I affinity and capacity are used this may simplify insulin binding data interpretation.