Sulfonylureas such as gliclazide stimulate insulin secretion from pancreatic beta cells by which primary molecular mechanism?

• A Closure of ATP-sensitive potassium channels, causing membrane depolarization ✓
• B Activation of glucagon-like peptide-1 receptors on the beta cell
• C Inhibition of potassium channels opened by cyclic AMP
• D Direct opening of voltage-gated calcium channels

Explanation

Sulfonylureas bind the SUR1 subunit of the beta-cell ATP-sensitive K channel, closing it. The resulting depolarization opens voltage-gated calcium channels, calcium influx triggers exocytosis of insulin. This action is independent of ambient glucose concentration, which explains their hypoglycemia risk. Option B describes incretin-based drugs, and option D reverses the actual sequence since calcium entry follows depolarization rather than being a direct drug effect.

Reference: Katzung Basic and Clinical Pharmacology, 15th ed.

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