Thiazolidinediones (glitazones) such as pioglitazone cause peripheral insulin sensitisation but are associated with fluid retention and heart failure. The molecular target of pioglitazone is:
- A Peroxisome proliferator-activated receptor gamma (PPAR-gamma) — a nuclear receptor regulating adipogenesis and insulin-sensitising gene expression ✓
- B Adenylyl cyclase, increasing cAMP and activating PKA in adipose tissue
- C Glucagon receptor, suppressing hepatic glucose output via reduced glucagon signalling
- D Insulin receptor tyrosine kinase, acting as an allosteric enhancer of insulin binding
Explanation
Pioglitazone binds to PPAR-gamma, a nuclear receptor highly expressed in adipose tissue and macrophages. Activated PPAR-gamma forms a heterodimer with RXR and binds to peroxisome proliferator response elements (PPREs), inducing transcription of insulin-sensitising genes (e.g., GLUT4, adiponectin, fatty acid binding proteins) and promoting adipocyte differentiation. This redistributes lipid from visceral to subcutaneous depots and improves insulin signalling in peripheral tissues. Fluid retention occurs due to PPAR-gamma activation of collecting duct ENaC expression. Rosiglitazone (another TZD) was restricted due to cardiovascular safety concerns.
Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.