How does insulin regulate glucose uptake in skeletal muscle and adipose tissue?

• A. Insulin activates AMPK to translocate GLUT2 to surface.
• B. Insulin activates PI3K-AKT causing GLUT4 translocation; exercise via AMPK also can enhance GLUT4 translocation.
• C. Insulin inhibits GLUT4 translocation to slow glucose uptake.
• D. Glucose uptake occurs independently of insulin in skeletal muscle.

Answer: (B)

Glucose uptake in skeletal muscle and adipose tissue mainly depends on mobilizing GLUT4 transporters to the cell surface in response to insulin. When insulin binds its receptor, a signaling cascade activates PI3K and then AKT. Activated AKT phosphorylates targets such as AS160/TBC1D4, which relieves brakes on Rab GTPases and triggers GLUT4-containing vesicles to move to and fuse with the plasma membrane. The result is more GLUT4 at the surface and increased glucose entry from the blood into these tissues.

Exercise or muscle contraction can also boost GLUT4 translocation, but through a different route: AMPK activation. This insulin-independent pathway helps explain why glucose uptake rises during and after exercise even when insulin levels are not high.

GLUT2 is not the transporter involved in this insulin-stimulated process in muscle and fat, which is why choices invoking GLUT2 or claiming glucose uptake is insulin-independent in these tissues don’t fit.