Which drug acts on PPAR gamma receptors?
**Core Concept**
The peroxisome proliferator-activated receptor gamma (PPAR gamma) is a nuclear receptor that plays a crucial role in regulating glucose and lipid metabolism. Activation of PPAR gamma leads to the expression of genes involved in glucose uptake, lipid synthesis, and adipogenesis.
**Why the Correct Answer is Right**
Pioglitazone is a thiazolidinedione (TZD) that acts as an agonist at PPAR gamma receptors. By binding to PPAR gamma, pioglitazone enhances the transcription of genes involved in glucose uptake, such as glucose transporter type 4 (GLUT4), leading to improved insulin sensitivity and glycemic control in type 2 diabetes mellitus. This results in increased glucose uptake in adipose tissue and skeletal muscle.
**Why Each Wrong Option is Incorrect**
**Option A:** Metformin is a biguanide that acts by inhibiting mitochondrial respiratory chain complex 1, leading to decreased hepatic glucose production and increased insulin sensitivity, but it does not act on PPAR gamma receptors.
**Option B:** Rosiglitazone is another thiazolidinedione that also acts on PPAR gamma receptors, but it was withdrawn from the market due to increased cardiovascular risk, making pioglitazone a safer alternative.
**Option C:** Sitagliptin is a dipeptidyl peptidase-4 (DPP-4) inhibitor that enhances the levels of incretin hormones, leading to increased insulin secretion and decreased glucagon levels, but it does not act on PPAR gamma receptors.
**Clinical Pearl / High-Yield Fact**
Thiazolidinediones, including pioglitazone, may cause fluid retention and increased risk of heart failure, especially in patients with pre-existing heart failure or edema.
**Correct Answer: C. Pioglitazone**