{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T18:20:51Z","timestamp":1785522051105,"version":"3.56.0"},"reference-count":41,"publisher":"American Diabetes Association","issue":"7","license":[{"start":{"date-parts":[[2021,8,27]],"date-time":"2021-08-27T00:00:00Z","timestamp":1630022400000},"content-version":"vor","delay-in-days":3360,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/3.0\/"}],"content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2012,7,1]]},"abstract":"<jats:sec>\n                  <jats:title\/>\n                  <jats:p>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.<\/jats:p>\n               <\/jats:sec>","DOI":"10.2337\/db11-1241","type":"journal-article","created":{"date-parts":[[2012,5,15]],"date-time":"2012-05-15T06:29:45Z","timestamp":1337063385000},"page":"1838-1847","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":65,"title":["Uncoupling Endothelial Nitric Oxide Synthase Is Ameliorated by Green Tea in Experimental Diabetes by Re-establishing Tetrahydrobiopterin Levels"],"prefix":"10.2337","volume":"61","author":[{"given":"Aline M.","family":"Faria","sequence":"first","affiliation":[{"name":"Renal Pathophysiology Laboratory, Investigation on Diabetes Complications, Faculty of Medical Sciences, State University of Campinas (Unicamp), 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