Resveratrol prevents interleukin-1 beta-induced dysfunction of pancreatic beta-cells

Objective: Interleukin-1 beta (IL-1 beta) plays an important role in the development of type 1 and type 2 diabetes mellitus. Resveratrol, a polyphenol, is known to have a wide range of pharmacological properties in vitro. In this research, we examined the effects of resveratrol on IL-1 beta-induced beta-cell dysfunction. Methods: We first evaluated the effect of resveratrol on nitric oxide (NO) formation in RINm5F cells stimulated with IL-1 beta using the Griess method. Next, we performed transient transfection and reporter assays to measure the transcriptional activity of peroxisome proliferator-activated receptor-gamma (PPAR-gamma). We also used Western blotting analysis to assess the effect of resveratrol on inducible nitric oxide synthase (iNOS) expression and nuclear factor-kappa B (NF-kappa B) translocation to the nuclei in cells treated with IL-1 beta. In addition, we assessed the transcriptional activity of NF-kappa B using an electrophoretic mobility shift assay (EMSA). Finally, we evaluated the effect of resveratrol on IL-1 beta-induced inhibition of glucose-stimulated insulin secretion in freshly isolated rat pancreatic islets. Results: Resveratrol significantly suppressed IL-1 beta-induced NO production, a finding that correlated well with reduced levels of iNOS mRNA and protein. The molecular mechanism by which resveratrol inhibited iNOS gene expression appeared to involve increased PPAR-gamma activity, which resulted in the inhibition of NF-kappa B activation. Further analysis showed that resveratrol could prevent IL-1 beta-induced inhibition of glucose-stimulated insulin secretion in rat islets. Conclusion: In this study, we demonstrated that resveratrol could protect against pancreatic beta-cell dysfunction caused by IL-1 beta.