Long-term regulation of hexose transport by insulin in cultured mouse (3T3) adipocytes

Observations in vivo suggest that insulin acts as a long-term regulator of hexose uptake in fat cells. In the present study, we examined the long-term effect of insulin on hexose uptake in vitro. Exposure of fully differentiated mouse 3T3-L1 adipocytes to insulin induced a time-, concentration-, and protein synthesis-dependent increase in basal 2-deoxyglucose uptake (up to 40%) and a decrease in the 'acute' insulin response. The decrease in insulin effect was due to post-receptor alterations, since insulin binding was not substantially altered. The increase in basal 2-deoxyglucose uptake was due to an increase in the apparent Vmax of the transport system rather than to the observed increase (30%) in hexokinase activity, since the concentration of non-phosphorylated 2-deoxyglucose inside the cell was far below the extracellular concentration. The increase in apparent Vmax was most likely due to a protein synthesis-dependent increase in de novo synthesis of hexose transporters. Glucose was not essential for the effect. The mechanism responsible for the loss in insulin response remains to be solved. It can be concluded that insulin has the ability to act as a long-term regulator of hexose uptake in fat cells in vitro.