摘要
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-inducedβ-cell dysfunction.Methods：We first evaluated the effect of resveratrol on nitric oxide（NO）formation in RINm5F cells stimulated with IL-1βusing the Griess method.Next,we performed transient transfection and reporter assays to measure the transcriptional activity 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）translocation 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-γactivity,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.Conclusion：In this study,we demonstrated that resveratrol could protect against pancreaticβ-cell dysfunction caused by IL-1β.
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-inducedβ-cell dysfunction.Methods：We first evaluated the effect of resveratrol on nitric oxide（NO）formation in RINm5F cells stimulated with IL-1βusing the Griess method.Next,we performed transient transfection and reporter assays to measure the transcriptional activity 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）translocation 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-γactivity,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.Conclusion：In this study,we demonstrated that resveratrol could protect against pancreaticβ-cell dysfunction caused by IL-1β.
基金
supported by grants from the National Natural Science Foundation of China(No.30370676 and No.30771041)
the Special Funds for Major State Basic Research Program of China(973Program,No.2006CB503908)
