Regulation of glucose transport activity and expression of glucose transporter mRNA by serum, growth factors and phorbol ester in quiescent mouse fibroblasts

Abstract

We have investigated the effects of growth factors such as serum, platelet-derived growth factor (PDGF) and fibroblast growth factor (FGF) on glucose transport activity in quiescent mouse Swiss 3T3 cells. DNA synthesis was synchronously induced by either calf serum, or platelet-poor plasma in combination with PDGF or FGF. Early stimulation of glucose transport in the quiescent cells was also caused by serum, or by either PDGF or FGF. The time courses for the stimulation of transport were identical for serum, PDGF and FGF, and the stimulated uptake in each case was associated with a 5-6-fold increase in Vmax. There were no detectable changes in apparent Km. Expression of glucose transporter mRNA was also enhanced by these growth factors. By contrast, EGF, insulin and platelet-poor plasma had little effect on glucose transport and transporter-gene expression, although uridine uptake was enhanced by all of these growth factors. These results suggest that cell cycle-dependent stimulation of glucose transport and expression of the transporter mRNA are regulated by a specific class of growth factors such as PDGF and FGF. The tumor promoter phorbol 12-myristate 13-acetate (PMA) also stimulated glucose transport and expression of transporter mRNA in quiescent 3T3 cells. These stimulations were absent in PMA-pretreated cells. However, serum, PDGF and FGF were able to stimulate glucose transport as well as expression of the transporter mRNA in PMA-pretreated cells, suggesting that there are at least two independent pathways for regulating glucose transport and glucose transporter mRNA level in quiescent fibroblasts.