Expression and functional activity of PPARγ in pancreatic β cells

摘要: Rosiglitazone is an agonist of peroxisome proliferator activated receptor-γ (PPARγ) and ameliorates insulin resistance in type II diabetes. In addition, it may also promote increased pancreatic β-cell viability, although not known whether this effect mediated by a direct action on the β cell. We have investigated possibility. Semiquantitative real-time reverse transcription–polymerase chain reaction analysis (Taqman®) revealed that freshly isolated rat islets clonal line, BRIN-BD11, express PPARγ, as well PPARα PPARδ. The levels expression PPARγ were estimated reference to adipose tissue found represent approximately 60% (islets) 30% (BRIN-BD11) visceral tissue. Western blotting confirmed presence immunoreactive (and human) BRIN-BD11 cells. Transfection cells with PPARγ-sensitive luciferase reporter construct was used evaluate functional competence endogenous PPARγ. Luciferase activity modestly putative ligand, 15-deoxy-Δ12,14 prostaglandin J2 (15dPGJ2). caused activation but required concentrations drug (50–100 μM) are beyond expected therapeutic range. This suggests relatively insensitive rosiglitazone cells. Exposure lipotoxic effector, palmitate, marked loss viability. attenuated treatment either actinomycin D or cycloheximide suggesting pathway programmed cell death involved. failed protect from toxic actions palmitate at up 50 μM. Similar results obtained range other agonists. Taken together, present data suggest that, least under vitro conditions, thiazolidinediones do exert protective effects against fatty acid-mediated cytotoxicity cells. British Journal Pharmacology (2004) 142, 1162–1170. doi:10.1038/sj.bjp.0705844