In insulin signaling, which protein acts immediately downstream of the receptor to promote GLUT4 translocation?

• A. MAPK
• B. JAK2
• C. AKT
• D. GSK3

Answer: (C)

When insulin binds its receptor, the signal moves from the receptor through an IRS-1–PI3K axis and builds up PIP3 at the membrane. This recruits AKT to the membrane, where it is activated and then phosphorylates substrates that control vesicle trafficking. The key target for GLUT4 translocation is AS160/TBC1D4, and AKT phosphorylation relieves its inhibition on GLUT4-containing vesicles, enabling them to move to and fuse with the plasma membrane to increase glucose uptake.

Other pathways listed don’t directly drive GLUT4 movement: the MAPK route mainly governs growth-related gene expression, JAK2 is more for cytokine signals, and GSK3 is a downstream substrate of AKT that AKT inhibits rather than directly promoting GLUT4 translocation.