Involvement of phosphatidylinositol 3-kinase in stimulation of glucose transport by growth factors in 3T3-L1 adipocytes

Activation of phosphatidylinositol 3-kinase (PI 3-kinase) appears to be part of the signalling mechanism by which insulin stimulates cellular glucose uptake. We have investigated the involvement of PI S-kinase in the regulation of glucose uptake in 3T3-L1 adipocytes by comparing the effects of platelet-derived growth factor (PDGF), epidermal growth factor (EGF), and insulin. Stimulation of [C-14]deoxyglucose uptake by PDGF and EGF was 29% and 70%, respectively, while that by insulin was 5-fold. Wortmannin, a PI 3-kinase inhibitor, completely blocked the effects of all three agonists. The relative effects of the growth factors on phosphatidlyinositol-trisphosphate (PIP3) synthesis were also determined. Insulin caused a large increase in this phosphoinositide. The effect of PDGF was much smaller, in fact barely detectable, while EGF had no detectable effect. The results suggest a role for PI 3-kinase in stimulation of glucose uptake by PDGF and EGF. However, the degree of PI 3-kinase by these growth factors appears to be much smaller than that by insulin, consistent with smaller stimulations of glucose transport.