Inhibitors of phosphoinositide 3-kinase block exocytosis but not endocytosis of transferrin receptors in 3T3-L1 adipocytes.

The role of PI 3-kinase in transferrin receptor recycling was investigated in 3T3-L1 adipocytes. Wortmannin, a specific PI 3-kinase inhibitor, blocked insulin stimulated recruitment of transferrin receptors to the plasma membrane (IC50 approximately 5-15 nM) with a similar potency to its inhibitory effects on PI 3-kinase and glucose transport. Wortmannin also blocked insulin stimulated recruitment of IGF-2 receptors to the cell surface. However, wortmannin (up to 200 nM) and another PI 3-kinase inhibitor, LY294002 (3 micrograms/ml), did not block transferrin receptor endocytosis. This demonstrates that while PI 3-kinase may be necessary for insulin stimulated exocytosis, it is not necessary for endocytosis of transferrin receptors.