| pubmed-article:19230846 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:19230846 | lifeskim:mentions | umls-concept:C0332307 | lld:lifeskim |
| pubmed-article:19230846 | lifeskim:mentions | umls-concept:C2700303 | lld:lifeskim |
| pubmed-article:19230846 | lifeskim:mentions | umls-concept:C1882726 | lld:lifeskim |
| pubmed-article:19230846 | lifeskim:mentions | umls-concept:C0017757 | lld:lifeskim |
| pubmed-article:19230846 | lifeskim:mentions | umls-concept:C0038836 | lld:lifeskim |
| pubmed-article:19230846 | lifeskim:mentions | umls-concept:C0068355 | lld:lifeskim |
| pubmed-article:19230846 | lifeskim:mentions | umls-concept:C0282625 | lld:lifeskim |
| pubmed-article:19230846 | lifeskim:mentions | umls-concept:C1879547 | lld:lifeskim |
| pubmed-article:19230846 | pubmed:issue | 3 | lld:pubmed |
| pubmed-article:19230846 | pubmed:dateCreated | 2009-6-22 | lld:pubmed |
| pubmed-article:19230846 | pubmed:abstractText | Glucose metabolism through the glycolysis and hexosamine pathway has been shown to be altered in type 2 diabetes. However, the fate of glucose through the pentose phosphate pathway (PPP) is currently unclear. In this study, we determined whether the activity of glucose-6-phosphate dehydrogenase (G6PD), the rate-limiting enzyme in the PPP, is modulated in the liver of Zucker obese fa/fa rats (9-11 weeks of age). We found that G6PD expression and activity, NADPH levels, and 6-phosphogluconate generation were significantly increased in the liver of fa/fa rats. Inhibition of PI3 kinase and Src kinases decreased (p < 0.05) G6PD activity in the fa/fa but not in the lean rat liver, suggesting that G6PD activity is regulated by PI3/Src kinase signaling pathways. G6PD-derived NADPH increased (p < 0.05) superoxide anion levels by 70-90% in fa/fa vs lean rat liver, which was inhibited by the NADPH oxidase inhibitor gp91(ds-tat) (50 microM) and G6PD inhibitors 6-aminonicotinamide (1 mM) and dehydroepiandrosterone (100 microM), therefore indicating that elevated G6PD activity may be responsible for mediating superoxide generation. Interestingly, we also found a positive correlation between liver hypertrophy/increased G6PD activity (r2 = 0.77; p = 0.0009) and liver hypertrophy/superoxide production (r2 = 0.51; p = 0.0091) in fa/fa rats. Increased G6PD and NADPH oxidase expression and activity, in young hyperglycemic and hyperinsulinemic rats before the development of diabetes, seems to be a contributing factor in the induction of oxidative stress. Because inhibition of G6PD activity decreases oxidative stress, we conclude that G6PD behaves as a pro-oxidant in the fa/fa rat liver in type 2 diabetes. | lld:pubmed |
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| pubmed-article:19230846 | pubmed:language | eng | lld:pubmed |
| pubmed-article:19230846 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:19230846 | pubmed:citationSubset | IM | lld:pubmed |
| pubmed-article:19230846 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
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| pubmed-article:19230846 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:19230846 | pubmed:month | Aug | lld:pubmed |
| pubmed-article:19230846 | pubmed:issn | 1873-4596 | lld:pubmed |
| pubmed-article:19230846 | pubmed:author | pubmed-author:GupteSachin... | lld:pubmed |
| pubmed-article:19230846 | pubmed:author | pubmed-author:WolinMichael... | lld:pubmed |
| pubmed-article:19230846 | pubmed:author | pubmed-author:GupteRakhee... | lld:pubmed |
| pubmed-article:19230846 | pubmed:author | pubmed-author:FloydBeverly... | lld:pubmed |
| pubmed-article:19230846 | pubmed:author | pubmed-author:UngvariZoltan... | lld:pubmed |
| pubmed-article:19230846 | pubmed:author | pubmed-author:GeorgeShimran... | lld:pubmed |
| pubmed-article:19230846 | pubmed:author | pubmed-author:KozickyMarkM | lld:pubmed |
| pubmed-article:19230846 | pubmed:author | pubmed-author:NeitoVanessaV | lld:pubmed |
