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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2011-2-22
pubmed:abstractText
Increased reactive oxygen species (ROS) induce pancreatic ?-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 ?-cell dysfunction through regulation of ROS accumulation and ?-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 ?-cell dysfunction, we assessed the levels of cellular ROS, glucose-stimulated insulin secretion and ?-cell apoptosis in G6PD-overexpressing pancreatic ?-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 ?-cell apoptosis, concomitant with the increase in proapoptotic gene expression. On the contrary, suppression of G6PD with small interference RNA attenuated palmitate-induced ?-cell apoptosis. Together, these data suggest that up-regulation of G6PD in pancreatic ?-cells would induce ?-cell dysregulation through ROS accumulation in the development of type 2 diabetes.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
1945-7170
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
152
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
793-803
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
G6PD up-regulation promotes pancreatic beta-cell dysfunction.
pubmed:affiliation
Department of Biological Sciences, Seoul National University, San 56-1, Sillim-Dong, Kwanak-Gu, Seoul 151-742, Korea.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't