Sulfonylureas lower blood glucose by what mechanism, and what is a major adverse effect?

• A. Stimulate glucagon release; Diarrhea
• B. Bind to KATP channels on pancreatic beta cells, causing depolarization and insulin release; Hypoglycemia and weight gain
• C. Increase insulin sensitivity in muscle; Edema
• D. Inhibit hepatic gluconeogenesis; Nausea

Answer: (B)

Sulfonylureas lower blood glucose by acting on pancreatic beta cells. They bind to the sulfonylurea receptor part of the KATP channel, causing the channel to close. This leads to membrane depolarization, opening voltage-gated calcium channels, and a rise in intracellular calcium that triggers exocytosis of insulin granules. The result is increased insulin release, helping lower blood glucose, but it relies on functional beta cells and can cause hypoglycemia, often with weight gain from the extra insulin. In contrast, drugs that stimulate glucagon release would raise glucose, those that increase insulin sensitivity act in muscle or fat, and those that inhibit hepatic gluconeogenesis (like metformin) work through different pathways.