Pioglitazone is a PPAR-gamma agonist. Which of the following best explains its mechanism of insulin sensitisation?
- A It increases GLUT-4 translocation to the plasma membrane in muscle by directly phosphorylating the insulin receptor substrate (IRS-1)
- B It acts as a nuclear receptor agonist, upregulating genes for adiponectin, GLUT-4, and fatty acid binding proteins, promoting fat redistribution from visceral to subcutaneous depots ✓
- C It inhibits hepatic gluconeogenesis via AMPK activation, similar to metformin
- D It stimulates glucagon-like peptide-1 secretion from intestinal L-cells, indirectly improving beta-cell function
Correct answer: B. It acts as a nuclear receptor agonist, upregulating genes for adiponectin, GLUT-4, and fatty acid binding proteins, promoting fat redistribution from visceral to subcutaneous depots
Explanation
Pioglitazone activates PPAR-gamma nuclear receptors predominantly in adipose tissue, upregulating genes encoding adiponectin (which increases muscle fatty acid oxidation and glucose uptake), GLUT-4, fatty acid binding proteins, and lipoprotein lipase. It redistributes fat from metabolically harmful visceral depots to subcutaneous depots. Unlike metformin, it does not act via AMPK, and unlike GLP-1 agonists, it does not affect incretin secretion.
Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.