Telomeres are proteineDNA complex structure at the ends of chromosomes,which are involved in genomic stability(Blackburn,2010).In most human cells,telomere erosion with each round of cell division eventually limits cell proliferation and tissue renewal,thereby impacting age-dependent pathologies(Lundblad,2012).Leukocyte telomere length(LTL)
Elevated uric acid causes direct injury to pancreaticβ-cells.In this study,we examined the effects of luteolin,an important antioxidant,on uric acid-inducedβ-cell dysfunction.We first evaluated the effect of luteolin on nitric oxide(NO)formation in uric acid-stimulated Min6 cells using the Griess method.Next,we performed transient transfection and reporter assays to measure transcriptional activity of nuclear factor(NF)-κB.Western blotting assays were also performed to assess the effect of luteolin on the expression of MafA and inducible NO synthase(iNOS)in uric acid-treated cells.Finally,we evaluated the effect of luteolin on uric acid-induced inhibition of glucose-stimulated insulin secretion(GSIS)in Min6 cells and freshly isolated mouse pancreatic islets.We found that luteolin significantly inhibited uric acid-induced NO production,which was well correlated with reduced expression of iNOS mRNA and protein.Furthermore,decreased activity of NF-κB was implicated in inhibition by luteolin of increased iNOS expression induced by uric acid.Besides,luteolin significantly increased MafA expression in Min6cells exposed to uric acid,which was reversed by overexpression of iNOS.Moreover,luteolin prevented uric acidinduced inhibition of GSIS in both Min6 cells and mouse islets.In conclusion,luteolin protects pancreaticβ-cells from uric acid-induced dysfunction and may confer benefit on the protection of pancreaticβ-cells in hyperuricemiaassociated diabetes.
Ying DingXuhui ShiXuanyu ShuaiYuemei XuYun LiuXiubin LiangDong WeiDongming Su
