Resveratrol protects RINm5F pancreatic cells from methylglyoxal-induced apoptosis

The effects of resveratrol on the prevention of apoptosis as well as insulin production are unclear. To examine the effects, we treated insulin-secreting beta cells with methylglyoxal (MG), a metabolite known to induce apoptosis and diabetes in the presence or absence of resveratrol. The MG treatment induced the expression of apoptotic signaling molecules and decreased insulin production. Pretreatment with resveratrol resulted in an increase in insulin synthesis via upregulation of peroxisome proliferator-activated receptor gamma (PPARgamma) and pancreatic-duodenal homeobox-1 (PDX-1). Resveratrol also inhibited MG-mediated expression of CCAAT/enhancer-binding protein beta (C/EBPbeta), a negative regulator of insulin production. Moreover, resveratrol strongly activated the expression of nuclear factor erythroid 2-related factor 2 (Nrf2), which resulted in the attenuation of oxidative stress. These results suggest that resveratrol can attenuate MG-induced oxidative stress in pancreatic cells and increase insulin levels.