Source:http://linkedlifedata.com/resource/pubmed/id/21248143
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
3
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pubmed:dateCreated |
2011-2-22
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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.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
AIM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Glucose,
http://linkedlifedata.com/resource/pubmed/chemical/Glucosephosphate Dehydrogenase,
http://linkedlifedata.com/resource/pubmed/chemical/Insulin,
http://linkedlifedata.com/resource/pubmed/chemical/Palmitates,
http://linkedlifedata.com/resource/pubmed/chemical/Reactive Oxygen Species
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
1945-7170
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pubmed:author | |
pubmed:issnType |
Electronic
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pubmed:volume |
152
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
793-803
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pubmed:dateRevised |
2011-11-17
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pubmed:meshHeading |
pubmed-meshheading:21248143-Animals,
pubmed-meshheading:21248143-Apoptosis,
pubmed-meshheading:21248143-Cell Line, Tumor,
pubmed-meshheading:21248143-Gene Expression Regulation, Enzymologic,
pubmed-meshheading:21248143-Glucose,
pubmed-meshheading:21248143-Glucosephosphate Dehydrogenase,
pubmed-meshheading:21248143-Insulin,
pubmed-meshheading:21248143-Insulin-Secreting Cells,
pubmed-meshheading:21248143-Mice,
pubmed-meshheading:21248143-Mice, Inbred NOD,
pubmed-meshheading:21248143-Palmitates,
pubmed-meshheading:21248143-Rats,
pubmed-meshheading:21248143-Rats, Sprague-Dawley,
pubmed-meshheading:21248143-Reactive Oxygen Species,
pubmed-meshheading:21248143-Up-Regulation
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pubmed:year |
2011
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pubmed:articleTitle |
G6PD up-regulation promotes pancreatic beta-cell dysfunction.
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pubmed:affiliation |
Department of Biological Sciences, Seoul National University, San 56-1, Sillim-Dong, Kwanak-Gu, Seoul 151-742, Korea.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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