Luteolin prevents uric acid-induced pancreatic β-cell dysfunction  

作　　者：Ying Ding Xuhui Shi Xuanyu Shuai Yuemei Xu Yun Liu Xiubin Liang Dong Wei Dongming Su 

机构地区：[1]Center of Metabolic Disease Research,Nanjing Medical University [2]Department of Endocrinology,the Second People's Hospital of Chengdu [3]Center of Cellular Therapy,the Second Affiliated Hospital of Nanjing Medical University

出　　处：《The Journal of Biomedical Research》2014年第4期292-298,共7页生物医学研究杂志（英文版）

基　　金：supported by the National Basic Research Program ofChina(2011CB504000,Program 973);the National Natural ScienceFoundation of China(81070656,81171589);the Colleges andUniversities in Jiangsu Province Plans to Graduate Research andInnovation(No.CXZZ12_0562)and Grant(No.100011)from the HealthDepartment of Sichuan Province to D.W

摘　　要：Elevated uric acid causes direct injury to pancreatic β-cells. In this study, we examined the effects of luteolin, an important antioxidant, on uric acid-induced β-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 acidinduced 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 Min6 cells 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 pancreatic β-cells from uric acid-induced dysfunction and may confer benefit on the protection of pancreatic β-cells in hyperuricemiaassociated diabetes.Elevated uric acid causes direct injury to pancreatic β-cells. In this study, we examined the effects of luteolin, an important antioxidant, on uric acid-induced β-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 acidinduced 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 Min6 cells 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 pancreatic β-cells from uric acid-induced dysfunction and may confer benefit on the protection of pancreatic β-cells in hyperuricemiaassociated diabetes.

关 键 词：LUTEOLIN uric acid nitric oxide nuclear factor （NF）-κB MAFA 

分 类 号：R285[医药卫生—中药学]