AJP - Endocrinology and Metabolism, Vol 247, Issue 5 667-E674, Copyright © 1984 by American Physiological Society
Kinetics of cell age-dependent decline of insulin receptors in human red cells
G. Baumann and J. G. MacCart
Insulin receptors are present in human erythrocytes and correlate
negatively with cellular age. Little is known about the function of these
receptors, about the precise kinetics of their decline during cell aging or
about their fate after disappearance from the cells. To elucidate some of
these questions, we have prepared red blood cell populations of widely
varying cellular ages (ranging from the erythroblast stage to senescent
mature erythrocytes) by isopycnic centrifugation on isosmolar density
gradients. In addition, young red cells were cultured for 4 days in vitro
to permit observation of short-term changes. In mature erythrocytes,
insulin receptors decreased as an exponential function of cell age with an
estimated half time of 40 days. A more rapid decline of insulin receptors
occurred coincident with reticulocyte maturation. Loss of receptors from
cultured cells was accompanied by appearance of a soluble insulin receptor
in the medium. The effect of insulin on glucose utilization in erythroblast
and reticulocyte preparations was negligible, as assessed by CO2 and
lactate production. We conclude that 1) insulin receptors are progressively
lost from the red blood cell after the erythroblast stage; 2) receptor loss
is particularly rapid during reticulocyte maturation; 3) shedding of
receptors into the extracellular environment is one reason for their
depletion from cells; and 4) in basophilic erythroblasts and reticulocytes,
insulin exhibits little metabolic action despite the relatively high
receptor complement present in these cells.
