Glucose-induced acceleration of deoxyglucose transport in rat adipocytes. Evidence for a second barrier to sugar entry

The transport of trace (a concentration much less than Km for transport) 2-deoxyglucose (deoxyglucose) and 3-O-methylglucose (methylglucose) into rat adipocytes was measured using 1- to 2-s pulses at 37 degrees C in the absence of glucose and in the presence of glucose with and without pre-exposure to glucose. Pre-exposure of insulin-stimulated adipocytes to 10 mM glucose for 30 min resulted in an acceleration of trace deoxyglucose transport above that seen in the absence of glucose. In contrast, when glucose was added together with deoxyglucose, an inhibition of transport was observed. There was no effect up to 5-min pre-exposure to 10 mM glucose, but acceleration appeared thereafter and reached a steady state by 30 min, i.e. a 3-fold higher transport rate than that seen when deoxyglucose and glucose were added together. Glucose (3.5 mM) appears to be a threshold concentration for this effect. A smaller effect was seen in the absence of insulin (1.5-fold) using 10 mM glucose and in the presence of insulin using 10 mM mannose (2.7-fold). No effect was seen using 10 mM galactose, fructose, pyruvate-lactate, deoxyglucose, and methylglucose. There was no effect of glucose pre-exposure on insulin-stimulated methylglucose transport. We propose that entry occurs across two independent barriers in series separated by an aqueous pore, that transport across the second barrier is more rate limiting for deoxyglucose than for methylglucose, and than metabolites of glucose decrease the resistance of the second barrier to deoxyglucose transport.