Resveratrol prevents interleukin-1β-induced dysfunction of pancreatic β-cells
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Graphical Abstract
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Abstract
Objective: Interleukin-1β (IL-1β) 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-1β-induced β-cell dysfunction. Methods: We first evalu-ated the effect of resveratrol on nitric oxide (NO) formation in RINm5F cells stimulated with IL-1β using the Griess method. Next, we performed transient transfection and reporter assays to measure the transcriptional activ-ity of peroxisome proliferator-activated receptor-γ (PPAR-γ). We also used Western blotting analysis to assess the effect of resveratrol on inducible nitric oxide synthase (iNOS) expression and nuclear factor-κB (NF-κB) translo-cation to the nuclei in cells treated with IL-1β. In addition, we assessed the transcriptional activity of NF-κB using an electrophoretic mobility shift assay (EMSA). Finally, we evaluated the effect of resveratrol on IL-1β–induced inhibition of glucose-stimulated insulin secretion in freshly isolated rat pancreatic islets. Results: Resveratrol significantly suppressed IL-1β-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-γ activity, which resulted in the inhibition of NF-κB activation. Further analysis showed that resveratrol could prevent IL-1β-induced inhibition of glucose-stimulated insulin secretion in rat islets. Con-clusion: In this study, we demonstrated that resveratrol could protect against pancreatic β-cell dysfunction caused by IL-1β.
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