Sulfonylureas such as gliclazide increase insulin secretion by which molecular action on the beta cell?

• A Prolonging the half-life of endogenous GLP-1
• B Opening voltage-gated calcium channels directly, independent of membrane potential
• C Inhibiting glucagon secretion from adjacent alpha cells
• D Binding SUR1 and closing the ATP-sensitive potassium channel, causing membrane depolarization ✓

Explanation

Sulfonylureas bind the SUR1 subunit of the beta cell KATP channel. Channel closure depolarizes the membrane, opens voltage-dependent calcium channels, and triggers insulin granule exocytosis. Because this action is independent of ambient glucose, sulfonylureas can cause hypoglycemia, unlike incretin-based drugs. Option A describes DPP-4 inhibitors, and option D versus direct calcium channel opening distinguishes sulfonylureas from meglitinides only in binding site, not in final pathway.

Reference: Goodman and Gilman's The Pharmacological Basis of Therapeutics, 14th ed.

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