Relationship between deactivation of insulin-stimulated glucose transport and insulin dissociation in isolated rat adipocytes

Abstract

The time course of 125I-insulin dissociation from receptors and deactivation of insulin-stimulated glucose transport was measured in rat adipocytes. When cells were incubated with a submaximally stimulating insulin concentration (1 ng/ml), insulin dissociated rapidly at 24 degrees C and 37 degrees C, with a t1/2 of 26 and 14 min, respectively. On the other hand, deactivation of 3-O-methylglucose transport proceeded at a much slower rate. The t1/2 of deactivation was 73 min at 24 degrees C and 43 min at 37 degrees C. Thus, the activated state of the glucose transport system persisted at a time when receptor occupancy had greatly decreased, and hormone dissociation was 3 times faster than deactivation; both processes were equally temperature-dependent. When glucose (1 mM) was omitted from the buffer, deactivation was essentially completely inhibited for at least 2 h despite the fact that the rate of insulin dissociation was unaffected.

In conclusion: 1) termination of the insulin signal on glucose transport can be separated from dissociation of insulin receptor complexes; 2) transport deactivation proceeds much more slowly than insulin dissociation and is dependent on some aspect of ongoing cellular metabolism.