FIG. 7.

Inhibition of NF-κB–mediated cytotoxic pathway and restoration of glucose-stimulated insulin secretion by resveratrol and Ad-SIRT1 in rat islets. Rat islets (30) were treated with IL-1β and IFN-γ with or without a 3-h pretreatment with resveratrol. DNA binding of NF-κB (A) was then determined 1 h later, and nitrite production and iNOS mRNA and protein expressions (B) were determined 24 h later. Rat islets (50) were infected with 1 × 10⁹ pfu Ad-SIRT1 or Ad-lacZ for 12 h and exposed to IL-1β and IFN-γ for 24 h. C: Islets extracts prepared 24 h after viral infection were subjected to Western blot analysis with anti-SIRT1 antibody. D: The effects of overexpressed SIRT1 on IL-1B–and IFN-γ–induced nitrite production, iNOS mRNA expression, and protein expression were determined. Rat islets (10) were treated with IL-1β and IFN-γ with or without a 3-h pretreatment with resveratrol or Ad-SIRT1 infection. E: After 24 h of incubation, glucose-stimulated insulin secretion was quantified. F: Islet viability was analyzed by microscopic analysis after staining with acridine orange and propidium iodide as described in research design and methods. Viable islets were counted manually and represented as percentage viability. Results of triplicate samples are expressed as the mean ± SE. **P < 0.01 vs. untreated control; ##P < 0.01 vs. IL-1β + IFN-γ.