Luteolin prevents uric acid-induced pancreatic b-cell dysfunction

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

doi:10.7555/JBR.28.20130170

Volume 28 Issue 4

Jul. 2014

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Ying Ding, Xuhui Shi, Xuanyu Shuai, Yuemei Xu, Yun Liu, Xiubin Liang, Dong Wei, Dongming Su. Luteolin prevents uric acid-induced pancreatic b-cell dysfunction[J]. The Journal of Biomedical Research, 2014, 28(4): 292-298. doi: 10.7555/JBR.28.20130170

Citation:

Ying Ding, Xuhui Shi, Xuanyu Shuai, Yuemei Xu, Yun Liu, Xiubin Liang, Dong Wei, Dongming Su. Luteolin prevents uric acid-induced pancreatic b-cell dysfunction[J]. The Journal of Biomedical Research, 2014, 28(4): 292-298. doi: 10.7555/JBR.28.20130170

Citation:

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Luteolin prevents uric acid-induced pancreatic b-cell dysfunction

doi: 10.7555/JBR.28.20130170

1.
Center of Metabolic Disease Research, Nanjing Medical University, Nanjing, Jiangsu 210029, China
2.
Center of Metabolic Disease Research, Nanjing Medical University, Nanjing, Jiangsu 210030, China
3.
Center of Metabolic Disease Research, Nanjing Medical University, Nanjing, Jiangsu 210031, China
4.
Center of Metabolic Disease Research, Nanjing Medical University, Nanjing, Jiangsu 210032, China
5.
Center of Metabolic Disease Research, Nanjing Medical University, Nanjing, Jiangsu 210033, China
6.
Center of Metabolic Disease Research, Nanjing Medical University, Nanjing, Jiangsu 210034, China
7.
Department of Endocrinology, the Second People9 s Hospital of Chengdu, Sichuan 610017, China
8.
Center of Metabolic Disease Research, Nanjing Medical University, Nanjing, Jiangsu 210036, China
9.
Center of Cellular Therapy, the Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, China

Funds:

This study was supported by the National Basic Research Program of China (2011CB504000, Program 973), the National Natural Science Foundation of China (81070656, 81171589), the Colleges and Universities in Jiangsu Province Plans to Graduate Research and Innovation (No.CXZZ12_0562) and Grant (No.100011) from the Health Department of Sichuan Province to D.W.

Received: 2013-10-23
Issue Date: 2014-07-28

Abstract

Abstract

Elevated uric acid causes direct injury to pancreatic b-cells. In this study, we examined the effects of luteolin, an important antioxidant, on uric acid-induced b-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)-kB. 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-kB 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 b-cells from uric acid-induced dysfunction and may confer benefit on the protection of pancreatic b-cells in hyperuricemiaassociated diabetes.
- luteolin,
- uric acid,
- nitric oxide,
- nuclear factor (NF)-kB,
- MafA