Insulin receptor signaling activates IRS-1 → PI3K → PIP3 → PDK1 → Akt pathway. Which downstream effect of Akt is responsible for acute GLUT4 translocation to the plasma membrane in muscle?

• A Phosphorylation and inactivation of GSK-3
• B Phosphorylation and inactivation of AS160 (TBC1D4) ✓
• C Activation of mTORC1 and S6 kinase
• D Phosphorylation of FOXO transcription factors

Explanation

GLUT4 vesicle trafficking to the plasma membrane is primarily regulated by Akt-mediated phosphorylation of AS160 (Akt substrate of 160 kDa, also called TBC1D4), a GTPase-activating protein (GAP) for Rab GTPases. In the basal state, AS160 keeps Rab proteins in the GDP-inactive form, retaining GLUT4 vesicles intracellularly. Akt phosphorylates and inactivates AS160, allowing Rab GTPases to become GTP-bound and active, enabling GLUT4 vesicle exocytosis. GSK-3 inactivation (option A) promotes glycogen synthesis; mTORC1 (option C) regulates protein synthesis; FOXO phosphorylation (option D) inhibits gluconeogenic gene transcription.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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