Insulin stimulates glucose transport through multiple signaling pathways. Insulin causes the release of glucose storage vesicles (GSV) from intracellular tethering sites. Additionally, insulin stimulates the binding of the vesicular protein VAMP2 to syntaxin-4, allowing for vesicle docking at the plasma membrane. It is likely that insulin promotes GSV trafficking to the plasma membrane via a PI 3-kinase/Akt–dependent signaling cascade, but uses a PI 3-kinase–independent pathway to regulate vesicular fusion with the cell membrane.