Journal
DIABETES
Volume 61, Issue 7, Pages 1838-1847Publisher
AMER DIABETES ASSOC
DOI: 10.2337/db11-1241
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Funding
- Fundacao de Amparo a Pesquisa do Estado de Sao Paulo [2008/57560-0]
- Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)
- CNPq
- Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) [08/57560-0] Funding Source: FAPESP
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The current study investigated the potential of green tea (GT) to improve uncoupling of endothelial nitric oxide synthase (eNOS) in diabetic conditions. In rats with streptozotocin-induced diabetes, nitric oxide (NO) bioavailability was reduced by uncoupling eNOS, characterized by a reduction in tetrahydrobiopterin (BH4) levels and a decrease in the eNOS dimer-to-monomer ratio. GT treatment ameliorated these abnormalities. Moreover, immortalized human mesangial cells (ihMCs) exposed to high glucose (HG) levels exhibited a rise in reactive oxygen species (ROS) and a decline in NO levels, which were reversed with GT. BH4 and the activity of guanosine triphosphate cyclohydrolase I decreased in ihMCs exposed to HG and was normalized by GT. Exogenous administration of BH4 in ihMCs reversed the HG-induced rise in ROS and the decline in NO production. However, coadministration of GT with BH4 did not result in a further reduction in ROS production, suggesting that reduced ROS with GT was indeed secondary to uncoupled eNOS. In summary, GT reversed the diabetes-induced reduction of BH4 levels, ameliorating uncoupling eNOS, and thus increasing NO bioavailability and reducing oxidative stress, two abnormalities that are involved in the pathogenesis of diabetic nephropathy. Diabetes 61:1838-1847, 2012
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