Insulin exerts its anabolic effects primarily through which intracellular signalling cascade that ultimately activates glycogen synthase and inhibits glycogen synthase kinase-3 (GSK-3)?

• A Adenylyl cyclase → cAMP → PKA → phosphorylation of CREB
• B Receptor tyrosine kinase → IRS-1 → PI3K → Akt (PKB) → GSK-3 phosphorylation (inactivation) ✓
• C JAK2 → STAT5 → transcription of anabolic genes
• D PLC → DAG → PKC → activation of MAP kinase

Explanation

Insulin receptor is a receptor tyrosine kinase (RTK). On insulin binding, auto-phosphorylation activates IRS-1/IRS-2 → PI3K → PIP3 → PDK1 → Akt (PKB). Akt phosphorylates and thereby inactivates GSK-3; inactive GSK-3 cannot phosphorylate glycogen synthase, leaving glycogen synthase in its active (dephosphorylated) form, promoting glycogen synthesis. Akt also promotes GLUT4 translocation. The cAMP/PKA and JAK/STAT pathways are used by glucagon and growth hormone respectively.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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