Pioglitazone is a PPAR-gamma agonist. Its mechanism of improving insulin sensitivity involves which molecular event?

• A Direct activation of insulin receptor kinase domain enhancing downstream IRS-1 phosphorylation
• B Transcriptional upregulation of GLUT4 and adiponectin, improving glucose uptake and fatty acid metabolism ✓
• C Inhibition of glycogen phosphorylase reducing hepatic glucose output
• D Stimulation of pancreatic beta cells increasing insulin secretion in a glucose-independent manner

Explanation

Pioglitazone binds PPAR-gamma (peroxisome proliferator-activated receptor gamma) in adipocytes, adipose tissue, and muscle. This nuclear receptor complex with RXR transcriptionally upregulates multiple genes: GLUT4 (improving glucose uptake), adiponectin (improving fatty acid oxidation and hepatic insulin sensitivity), and reduces fatty acid flux to liver and muscle. It does not directly activate the insulin receptor, inhibit glycogen phosphorylase (which is metformin's secondary mechanism), or stimulate beta cells.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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