Metformin's primary mechanism of action in reducing hepatic glucose production involves activation of which enzyme?

• A Pyruvate kinase, shunting glucose toward glycolysis
• B Glycogen synthase, promoting hepatic glycogen storage and reducing glucose output
• C AMP-activated protein kinase (AMPK), which inhibits PEPCK and G6Pase transcription and reduces gluconeogenesis ✓
• D Glucokinase, trapping glucose as glucose-6-phosphate in hepatocytes

Explanation

Metformin inhibits mitochondrial complex I in hepatocytes, raising the AMP:ATP ratio and activating AMPK. Activated AMPK phosphorylates and inhibits the transcriptional coactivator TORC2, reducing expression of PEPCK and glucose-6-phosphatase — the key gluconeogenic enzymes. The net effect is suppressed hepatic glucose output. Metformin also increases peripheral insulin sensitivity and reduces intestinal glucose absorption. It does not stimulate insulin secretion, hence no hypoglycaemia risk.

Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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