Time course of insulin-receptor binding and insulin-induced lipogenesis in isolated rat fat cells.

Insulin binding and action were studied in fat cells from the gluteal region of young healthy subjects. Fat cells from females were larger than those of males, had higher insulin receptor binding and higher rates of noninsulin-stimulated and maximally insulin-stimulated rates of methylglucose transport and glucose metabolism when these data were expressed per cell number. However, when insulin binding and insulin effects were expressed per cell surface, which may be physiologically more relevant, no sex differences were found in insulin binding and glucose transport, whereas noninsulin-stimulated and maximally insulin-stimulated glucose metabolism was still significantly increased in female fat cells. The latter indicates postreceptor differences in glucose metabolism between females and males. The insulin concentrations causing half-maximal responses (a measure of the sensitivity to insulin) of glucose transport, glucose metabolism and lipolysis were similar in fat cells from the two sexes, which is consistent with the comparable values of insulin receptor binding when adjusted to cell surface. Studies of rate-determining steps for the glucose utilization of human fat cells showed that glucose transport was not the rate-limiting step at physiological glucose concentrations. Moreover, at physiological glucose levels, glucose metabolism exhibited a decreased maximal insulin responsiveness and an increased insulin sensitivity when compared with glucose metabolism at low glucose concentrations at which glucose transport is rate limiting for the fat cell glucose utilization.

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Relation of insulin receptor occupancy and deactivation of glucose transport

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1982.242.4.e234 ◽

1982 ◽

Vol 242 (4) ◽

pp. E234-E240

Author(s):

H. U. Haring ◽

E. Biermann ◽

W. Kemmler

Keyword(s):

Insulin Receptor ◽

Glucose Transport ◽

Receptor Occupancy ◽

Fat Cells ◽

Temperature Dependency ◽

Insulin Effect ◽

Kinetics Of ◽

Rat Fat Cells ◽

Isolated Rat ◽

Activation Phase

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.

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