Insulin receptor signalling activates PI3K/Akt pathway. Which immediate downstream substrate of Akt is phosphorylated to allow GLUT4 vesicle fusion with the plasma membrane in adipocytes?

• A IRS-1
• B GSK-3β
• C mTORC1
• D AS160 (TBC1D4) ✓

Explanation

AS160 (Akt substrate of 160 kDa, also called TBC1D4) is a Rab-GAP protein phosphorylated by Akt upon insulin stimulation. In the unphosphorylated state, AS160 keeps Rab proteins in the GDP-bound inactive form, retaining GLUT4 vesicles intracellularly. Akt phosphorylation of AS160 inactivates its GAP activity, allowing Rab proteins to remain GTP-bound and facilitating GLUT4 vesicle translocation and fusion with the plasma membrane. IRS-1 is upstream of PI3K. GSK-3β phosphorylation by Akt promotes glycogen synthesis. mTORC1 is involved in protein synthesis, not GLUT4 trafficking.

Reference: Harper's Illustrated Biochemistry, 32nd ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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