Dimerumic acid protects pancreas damage and elevates insulin production in methylglyoxal-treated pancreatic RINm5F cells

作者：Lee Bao Hong; Hsu Wei Hsuan; Hsu Ya Wen; Pan Tzu Ming^*

来源：Journal of Functional Foods, 2013, 5(2): 642-650.

DOI：10.1016/j.jff.2012.12.007

• Dimerumic acid (DMA)
• Pancreatic RINm5F cells
• Methylglyoxal (MG)
• Nuclear factor-erythroid2-related factor 2 (Nrf2)
• Insulin

The effects of dimerumic acid (DMA) on apoptosis prevention and insulin production in the glucose metabolite methylglyoxal (MG)-treated pancreatic RINm5F cells were evaluated. MG was found to induce apoptotic signal molecules mediated by oxidative stress in RINm5F cells, including caspase-3 and caspas-9, resulting in cell death and decreasing insulin production. In addition, DMA elevated insulin synthesis via up-regulating mammalian homologue of avian MafA/L-Maf (Maf-A) and pancreatic-duodenal homeobox-1 (PDX-1) and inhibited MG-mediated CCAAT/enhancer binding proteins-beta (C/EBP beta) expression, which is a negative regulator for insulin production. Nuclear factor-erythroid2-related factor 2 (Nrf2) is essential for antioxidant responsive element (ARE)-mediated induction. Results indicated that nuclear translocation of Nrf2 was promoted by DMA in MG-treated RINm5F cells to increase heme oxygenase-1 (HO-1) and glutamate-cysteine ligase (GCL) expressions. We confirmed that DMA protected PDX-1, Maf-A, and insulin production against MG-induced oxidative stress mediating by Nrf2 in Nrf2-knockdown RINm5F cells. These results suggest that DMA exerts antioxidative ability to attenuate MG-induced pancreatic cell damage and elevates insulin level to improve diabetes.

• 出版日期2013-4