What is the primary mechanism of action of thiazolidinediones?

• A. Increase insulin secretion
• B. Decrease gluconeogenesis
• C. Decrease insulin resistance
• D. Delay carbohydrate absorption

Answer: (C)

Thiazolidinediones act as activators of the PPAR-gamma receptor, which is a nuclear transcription factor found in fat, muscle, and liver. When PPAR-gamma is activated, it changes the expression of genes that enhance how tissues respond to insulin. The result is increased glucose uptake in muscle and adipose tissue and reduced hepatic glucose production, leading to lower blood glucose without increasing insulin secretion. This makes the primary mechanism decreasing insulin resistance.

They do not directly boost insulin secretion from the pancreas, which is why options describing increased insulin release aren’t the driving action. They also don’t directly block carbohydrate absorption from the gut, and while improving insulin sensitivity can lessen hepatic glucose output, the defining effect is improved insulin action in target tissues rather than a direct suppression of gluconeogenesis.