A 63-year-old female presents to clinic for a diabetes follow-up. She has been taking metformin for 3 years now, but her blood sugars have not been well controlled over the past year. Her average morning fasting blood sugar is 165 mg/dL, and her 2-h postprandial is 205 mg/dL. Glimepiride is added to her regimen. What is the mechanism of action of glimepiride?
(A) Decreased glucagon release
(B) Increased insulin release
(C) Increased insulin sensitivity in peripheral tissues
(D) Inhibits hepatic gluconeogenesis
(E) Inhibits intestinal brush border enzymes
The Correct Answer and Explanation is :
The correct answer is (B) Increased insulin release.
Explanation:
Glimepiride is a second-generation sulfonylurea, a class of drugs used to treat type 2 diabetes. The mechanism of action of glimepiride primarily involves increasing insulin release from pancreatic beta cells.
Sulfonylureas, like glimepiride, bind to specific receptors on the ATP-sensitive potassium channels (K_ATP channels) located on the surface of pancreatic beta cells. This binding leads to closure of these channels, which causes depolarization of the cell membrane. The depolarization opens voltage-gated calcium channels, allowing calcium to enter the beta cells. The increase in intracellular calcium triggers the release of insulin from the beta cells into the bloodstream.
This mechanism helps lower blood glucose levels by promoting insulin secretion, which facilitates the uptake of glucose by various tissues (e.g., muscle, fat) and the suppression of hepatic glucose production.
Why the other choices are incorrect:
- (A) Decreased glucagon release: While some medications, such as GLP-1 receptor agonists, can reduce glucagon secretion, sulfonylureas primarily work by increasing insulin release rather than directly inhibiting glucagon release.
- (C) Increased insulin sensitivity in peripheral tissues: Drugs like metformin or thiazolidinediones (TZDs) improve insulin sensitivity in peripheral tissues. However, glimepiride does not affect insulin sensitivity directly; it works by increasing insulin secretion from the pancreas.
- (D) Inhibits hepatic gluconeogenesis: Metformin is known to reduce hepatic gluconeogenesis, but glimepiride does not have this action. Glimepiride primarily increases insulin release, and its effect is more focused on insulin secretion than on glucose production.
- (E) Inhibits intestinal brush border enzymes: This mechanism describes alpha-glucosidase inhibitors, such as acarbose, which inhibit carbohydrate digestion in the intestines. Glimepiride does not have this effect.
Thus, glimepiride’s primary mechanism is increased insulin release, making option (B) the correct answer.