Nutrient regulation of β cells NADPH - oxidase activity

In the presence of high glucose concentration (16.7 mM), pancreatic islets show increased activities of superoxide dismutase (SOD) and glutathione peroxidase (GSHPx). This activation may be a result of reactive oxygen species (ROS) stimulation, which is generated during glucose metabolism. NAD(P)H oxidase is mainly responsible for ROS production by phagocytic cells but its isoforms have been found in various other tissues. We have recently shown that PMA -an activator of protein kinase C (PKC)increases the ROS formation by pancreatic β cells in the presence or absence of glucose or palmitate. DPI (diphenylene iodonium), an inhibitor of NAD(P)H oxidase, decreases glucoseand palmitate-induced ROS production by isolated pancreatic islets. Supporting these observations, the expression of the p47PHOX and p67PHOX NAD(P)H oxidase subunits was demonstrated by Western blotting and three NAD(P)H oxidase components were found in pancreatic islets by RTPCR analysis: gp91PHOX, p22PHOX and p47PHOX. Immunohistochemical experiments showed that p47PHOX subunit is mainly found in insulin-producing cells. Glucose stimulation of ROS production by pancreatic islets occurs through a PKC-dependent activation of NAD(P)H oxidase and this effect is potentiated by palmitate. Therefore, activation of NAD(P)H oxidase in pancreatic islets may be involved in the pathogenesis of type II diabetes.