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

作　　者：Fang Chen Xiaohua Zhou Yan Lin Changwen Jing Tao Yang Yong Ji Yujie Sun Xiao Han 

机构地区：[1]Key Laboratory of Human Functional Genomics of Jiangsu Province,Clinical Diabetes Centre of Jiangsu Province,Nanjing Medical University,Nanjing 210029,Jiangsu Province,China [2]Department of Endocrinology,Jiangsu Diabetes Center,the First Affiliated Hospital,Nanjing Medical University,Nanjing2 10029,Jiangsu Province,China [3]Atherosclerosis Research Centre,Nanjing Medical University,Nanjing 210029,Jiangsu Province,China

出　　处：《The Journal of Biomedical Research》2010年第5期381-388,共8页生物医学研究杂志（英文版）

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)

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.

关 键 词：resveratrol interleukin-1β peroxisome proliferator-activated receptor-γ nitric oxide nuclear factor-κB. 

分 类 号：Q78[生物学—分子生物学] TS262.6[轻工技术与工程—发酵工程]