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

Bao Hong Lee, Wei Hsuan Hsu, Ya Wen Hsu, Tzu Ming Pan

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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-β (C/EBPβ) 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.

Original languageEnglish
Pages (from-to)642-650
Number of pages9
JournalJournal of Functional Foods
Issue number2
Publication statusPublished - 2013 Apr 1


All Science Journal Classification (ASJC) codes

  • Food Science
  • Medicine (miscellaneous)
  • Nutrition and Dietetics

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