12-0-tetradecanoylphorbol-13-acetatea and concanavalin a enhance glucose uptake in thymocytes by different mechanisms

Abstract

The effects of the tumor promoter 12–0‐tetradecanoylphorbol‐13‐acetate (TPA) and the plant lectin concanavalin A (Con A) on glucose uptake in murine thymocytes were studied. TPA induces a rapid dose‐dependent increase in the uptake of 2‐deoxyglucose and in the transport of 3–0‐methylglucose. Con A also elicits a time‐ and dose‐dependent enhancement of 2‐deoxyglucose uptake. The effect of Con A, however, is less pronounced. The effect of combined treatment of thymocytes with Con A and TPA is not additive. Cytochalasin B completely inhibits the basal, as well as TPA‐ and Con A‐enhanced, 2‐deoxyglucose uptake. Dexamethasone markedly inhibits basal 2‐deoxyglucose uptake, but is less inhibitory to enhanced 2‐deoxyglucose uptake induced by TPA and Con A. The effect of TPA on 2‐deoxyglucose uptake and 3–0‐methylglucose transport is refractory to inhibition by isobutyl methylxanthine, dibutyryl cyclic AMP, and ethyleneglycol tetraacetic acid. These agents markedly inhibit the enhancement of 2‐deoxyglucose (2‐DOG) uptake by Con A. p‐Bromophenacyl bromide, an inhibitor of phospholipase A₂, also selectively inhibits Con A enhancement of 2‐DOG uptake. Taken together, the results suggest that Con A and TPA exert their stimulatory effect on glucose uptake by different activating mechanisms, but they may share a final common transport pathway.