Pioglitazone, a thiazolidinedione, reduces insulin resistance primarily by acting as a full agonist at which nuclear receptor?

• A Liver X receptor α (LXRα), increasing ABCA1-mediated cholesterol efflux
• B Farnesoid X receptor (FXR), reducing hepatic gluconeogenesis
• C Pregnane X receptor (PXR), inducing hepatic glucose transporter expression
• D Peroxisome proliferator-activated receptor γ (PPARγ), promoting adipocyte differentiation and fatty acid storage ✓

Explanation

Thiazolidinediones are PPARγ agonists. PPARγ is a nuclear transcription factor highly expressed in adipose tissue; its activation promotes differentiation of preadipocytes into mature adipocytes, increases expression of GLUT4 and fatty acid uptake genes, and redistributes lipid from visceral to peripheral adipose tissue. The net result is reduced circulating free fatty acids, improved hepatic and peripheral insulin sensitivity, and improved glycaemic control. PPARγ agonism also alters adipokine profiles (increases adiponectin). The other listed receptors are not targets of thiazolidinediones.

Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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