| First Author | Lee JW | Year | 2011 |
| Journal | Endocrinology | Volume | 152 |
| Issue | 3 | Pages | 793-803 |
| PubMed ID | 21248143 | Mgi Jnum | J:173877 |
| Mgi Id | MGI:5050477 | Doi | 10.1210/en.2010-0606 |
| Citation | Lee JW, et al. (2011) G6PD up-regulation promotes pancreatic beta-cell dysfunction. Endocrinology 152(3):793-803 |
| abstractText | Increased reactive oxygen species (ROS) induce pancreatic beta-cell dysfunction during progressive type 2 diabetes. Glucose-6-phosphate dehydrogenase (G6PD) is a reduced nicotinamide adenine dinucleotide phosphate-producing enzyme that plays a key role in cellular reduction/oxidation regulation. We have investigated whether variations in G6PD contribute to beta-cell dysfunction through regulation of ROS accumulation and beta-cell gene expression. When the level of G6PD expression in pancreatic islets was examined in several diabetic animal models, such as db/db mice and OLEFT rats, G6PD expression was evidently up-regulated in pancreatic islets in diabetic animals. To investigate the effect of G6PD on beta-cell dysfunction, we assessed the levels of cellular ROS, glucose-stimulated insulin secretion and beta-cell apoptosis in G6PD-overexpressing pancreatic beta-cells. In INS-1 cells, G6PD overexpression augmented ROS accumulation associated with increased expression of prooxidative enzymes, such as inducible nitric oxide synthase and reduced nicotinamide adenine dinucleotide phosphate oxidase. G6PD up-regulation also caused decrease in glucose-stimulated insulin secretion in INS-1 cells and primary pancreatic islets. Moreover, elevated G6PD expression led to beta-cell apoptosis, concomitant with the increase in proapoptotic gene expression. On the contrary, suppression of G6PD with small interference RNA attenuated palmitate-induced beta-cell apoptosis. Together, these data suggest that up-regulation of G6PD in pancreatic beta-cells would induce beta-cell dysregulation through ROS accumulation in the development of type 2 diabetes. |
