The insulin receptor is an age-dependent integral component of the human erythrocyte membrane

Human erythrocytes were separated according to age to determine whether there is heterogeneity in the specific binding of 125I-insulin to red cells. The mean cell age of erythrocyte isolates was determined from the cumulative distribution frequency of the cells in an isotonic (290 milliosmolar) density gradient and confirmed by assay for pyruvate kinase, an age-dependent red cell enzyme. An IBM 2997 centrifugal cell separator was used to obtain larger quantities of younger erythrocytes from normal subjects. 125I-insulin binding to red cells including reticulocytes was found to decrease exponentially as a function of their mean cell age in 8 normal subjects. A change in receptor number rather than affinity appeared to account for the observed change in 125I-insulin binding. An exponential, age-dependent change in binding of a hormone to its cell membrane bound receptor has not previously been observed. Consistent with these results is the possibility that regulation of the red cell insulin receptor concentration takes place only in the younger red cells.