AJP - Endocrinology and Metabolism, Vol 242, Issue 4 234-E240, Copyright © 1982 by American Physiological Society
Relation of insulin receptor occupancy and deactivation of glucose transport
H. U. Haring, E. Biermann and W. Kemmler
Kinetics of association and dissociation of 125I-insulin and of activation
and deactivation of 3-O-methylglucose transport were determined in isolated
rat fat cells. Equilibrium bound insulin (7.5, 25, 100 microunits/ml)
dissociated with a t1/2 of 2 min (100 microunits/ml), 4 min (25
microunits/ml), and 16 min (7.5 microunits/ml). Consecutive deactivation of
transport is observed only in the presence of glucose (1 mM); the t1/2 of
deactivation is approximately 60 min (100 and 25 microunits/ml) and 20 min
(7.5 microunits/ml). At 15 degrees C, the t1/2 of dissociation (7.5
microunits/ml) is 25 min, and deactivation is not observed. Addition of
dithioerythritol (5 mM) during the association of insulin decreased the
binding rapidly; however, a reduced insulin effect was only seen if the
binding decreased during the early activation phase of transport. In
conclusion, the maintenance of the insulin effect on transport does not
require persistent receptor occupancy; dissociation and deactivation are,
with respect to kinetics, temperature dependency and requirement of
glucose, independent processes. Receptor occupancy probably only controls
the activation of transport; deactivation seems to be controlled by
postreceptor processes.
