Glucose-stimulated insulin secretion (GSIS) from the pancreatic β-cell involves closure of ATP-sensitive K⁺ (KATP) channels. The KATP channel is a hetero-octameric complex. Which subunit is targeted by sulfonylurea drugs, and which subunit contains the pore?

• A Kir6.2 is targeted by sulfonylureas; SUR1 contains the pore
• B SUR2A is the target in β-cells; Kir6.1 contains the pore
• C GluT2 (glucose transporter) is targeted; the pore is formed by SUR1 alone
• D SUR1 (sulfonylurea receptor 1) is targeted by sulfonylureas; Kir6.2 contains the pore ✓

Explanation

The β-cell KATP channel is an octamer: 4 Kir6.2 inwardly-rectifying K⁺ pore-forming subunits + 4 SUR1 (ABCC8) regulatory subunits. Sulfonylureas (glibenclamide, glipizide) bind to the SUR1 subunit, closing the channel independently of ATP, causing membrane depolarization → L-type Ca²⁺ channel opening → Ca²⁺ entry → insulin exocytosis. Activating Kir6.2 mutations cause permanent neonatal diabetes (diazoxide-treatable); inactivating mutations cause congenital hyperinsulinism. SUR2A/Kir6.1 or Kir6.2 variants are expressed in cardiac/vascular smooth muscle.

Reference: Guyton & Hall, Textbook of Medical Physiology, 14th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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