title: Luteolin prevents uric acid-induced pancreatic β-cell dysfunction.
abstract: 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 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 Min6 cells exposed to uric acid, which was reversed by overexpression of iNOS. Moreover, luteolin prevented uric acid-induced 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 hyperuricemia-associated diabetes.
authors: Center of Metabolic Disease Research, Nanjing Medical University, Nanjing, Jiangsu 210029, China.
authors: Ying
authors: Y
authors: Ding
authors: Center of Metabolic Disease Research, Nanjing Medical University, Nanjing, Jiangsu 210029, China.
authors: Xuhui
authors: X
authors: Shi
authors: Center of Metabolic Disease Research, Nanjing Medical University, Nanjing, Jiangsu 210029, China.
authors: Xuanyu
authors: X
authors: Shuai
authors: Center of Metabolic Disease Research, Nanjing Medical University, Nanjing, Jiangsu 210029, China.
authors: Yuemei
authors: Y
authors: Xu
authors: Center of Metabolic Disease Research, Nanjing Medical University, Nanjing, Jiangsu 210029, China.
authors: Yun
authors: Y
authors: Liu
authors: Center of Metabolic Disease Research, Nanjing Medical University, Nanjing, Jiangsu 210029, China.
authors: Xiubin
authors: X
authors: Liang
authors: Department of Endocrinology, the Second People's Hospital of Chengdu, Sichuan 610017, China.
authors: Dong
authors: D
authors: Wei
authors: Center of Metabolic Disease Research, Nanjing Medical University, Nanjing, Jiangsu 210029, China. ; Center of Cellular Therapy, the Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, China.
authors: Dongming
authors: D
authors: Su
keywords: MafA; luteolin; nitric oxide; nuclear factor (NF)-κB; uric acid