Resveratrol upregulates Nrf2 expression to attenuate methylglyoxal-induced insulin resistance in Hep G2 cells.
Oxidative stress can result in insulin resistance, a primary cause of type-2 diabetes. Methylglyoxal (MG), a highly reactive dicarbonyl metabolite generated during glucose metabolism, has also been confirmed to cause pancreatic injury and induce inflammation, thereby resulting in insulin resistance. Recently, resveratrol has been reported to exert antioxidant properties, protecting cells from the generation of reactive oxygen species (ROS). The aim of this study was to evaluate resveratrol activation of nuclear factor erythroid 2-related factor 2 (Nrf2) to attenuate MG-induced insulin resistance in Hep G2 cells. Therefore, the molecular signaling events affecting resveratrol-mediated heme oxygenase-1 (HO-1) and glyoxalase expression levels were further investigated in this study. Our findings indicated that resveratrol activated the extracellular signal-regulated kinase (ERK) pathway but not the p38 or c-Jun N-terminal kinase (JNK) pathways, subsequently leading to Nrf2 nuclear translocation and elevation of HO-1 and glyoxalase expression levels. Moreover, resveratrol significantly elevated glucose uptake and protected against MG-induced insulin resistance in Hep G2 cells. In contrast, depletion of Nrf2 by small interfering RNA (si-RNA) resulted in the abrogation of HO-1 and glyoxalase expression in the MG-treated resveratrol group in Hep G2 cells. Administration of an appropriate chemopreventive agent, such as resveratrol, may be an alternative strategy for protecting against MG-induced diabetes.
Department of Horticulture and Landscape Architecture, National Taiwan University, Taipei 10617, Taiwan, Republic of China.
An-Sheng
AS
Cheng
Yu-Hsiang
YH
Cheng
Chiu-Hsia
CH
Chiou
Tsu-Liang
TL
Chang
D048049:Extracellular Signal-Regulated MAP Kinases / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D051547:Heme Oxygenase-1 / Q000235:genetics; D056945:Hep G2 Cells; D006801:Humans; D006943:Hyperglycemia / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D007333:Insulin Resistance; D051267:NF-E2-Related Factor 2 / Q000235:genetics* / Q000378:metabolism; D011765:Pyruvaldehyde / Q000009:adverse effects; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects*
D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D013267:Stilbenes; D011765:Pyruvaldehyde; D051547:Heme Oxygenase-1; D048049:Extracellular Signal-Regulated MAP Kinases; D000077185:Resveratrol