Insulin Binding to Erythrocytes: A Negative Correlation with Red Cell Age*

Abstract

Although the human erythrocyte has been used to study insulin binding to its receptor, the specific erythroid cell responsible for insulin binding has not been determined. Therefore, in subjects with reticulocyte counts ranging from 0.5–20%, [¹²⁵I]insulin binding was measured and corrected for the number of either erythrocytes or reticulocytes. The binding of [¹²⁵I]- insulin to erythrocytes was similar to that shown for other cell types by a variety of binding criteria. Within any erythrocyte preparation, binding increased linearly with cell number; however, among 33 subjects, the level of specific [^l25I]insulin binding did not correlate with the number of erythrocytes (r = 0.006; P = NS). Instead, the level of specific [^l25I]insulin binding among subjects was better correlated with the number of reticulocytes (r = 0.74; P < 0.001). The greater the percentage of reticulocytes, the higher the binding, with the increase due to an increase in the total number of insulin receptors. Since the density of erythrocytes increases with cell age, erythrocytes were fractionated by cell densities, and [¹²⁵I]insulin binding was measured in each fraction. The level of specific [¹²⁵I]insulin binding was related inversely to the cell density; binding was highest in the least dense fraction (youngest cells) and decreased linearly as density (i.e. age) increased (r = −0.94; P ≤ 0:001). The alteration in insulin binding was due to a change in the number of insulin receptors. Thus, although the erythrocyte has insulin receptors, the level of insulin binding can be markedly altered by the age of the cell preparation. These findings demonstrate that the mean red cell age should be considered if erythrocyte preparations are to be used for monitoring insulin receptor status.