Which molecular event explains the insulin secretagogue action of sulfonylureas?
- A Closure of ATP-sensitive potassium channels on the pancreatic beta cell membrane ✓
- B Activation of hepatic AMP kinase, reducing gluconeogenesis
- C Inhibition of renal sodium-glucose cotransporter 2
- D Agonism of glucagon-like peptide-1 receptors on beta cells
Correct answer: A. Closure of ATP-sensitive potassium channels on the pancreatic beta cell membrane
Explanation
Sulfonylureas bind SUR1, a subunit of the beta-cell ATP-sensitive potassium channel, closing the channel. The resulting membrane depolarisation opens voltage-gated calcium channels, calcium enters, and preformed insulin granules are released. This mechanism is insulin-independent of ambient glucose, which explains both their efficacy and their propensity to cause hypoglycaemia. Option B describes metformin and option D describes incretin-based drugs such as sitagliptin and semaglutide.
Reference: Katzung's Basic and Clinical Pharmacology, 16th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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