The contribution of fructose and nitric oxide to oxidative stress in hamster islet tumor (HIT) cells through the inactivation of glutathione peroxidase

Reducing sugars, such as glucose and fructose, are known to play a role in the initiation of apoptosis in pancreatic beta-cells. The data collected in this study show that fructose increases H2O2 levels and lipid peroxidation of hamster islet tumor (HIT) cells, which originated from hamster pancreat ic beta-cells. In an attempt to clarify the mechanism of this oxidative str ess, we were able to show that glutathione peroxidase (GPx) is inactivated by fructose, and that mRNA expression of GPx is suppressed by fructose. Nit ric oxide (NO) is also known to bring about apoptosis. The presence of NO i ncreases intracellular peroxide levels in HIT cells as judged by flow cytom etric analysis. These data suggest that fructose and nitric oxide suppress the activity or expression of GPx, and, as a result, permit an increase in intracellular peroxides or lipid peroxidation. This represents a major cont ribution to the main mechanism of apoptosis by fructose and NO.