ArticleJournal of the American Society of Nephrology : JASN2013
Maintenance of endothelial guanosine triphosphate cyclohydrolase I ameliorates diabetic nephropathy.
Article in Journal of the American Society of Nephrology : JASN, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 34 citations in OpenAlex.
- Oxidative stress and the role of redox signalling in chronic kidney disease.Nature reviews. Nephrology · 2024Review
- Suppression of GCH1 Sensitizes Ovarian Cancer and Breast Cancer to PARP Inhibitor.Journal of oncology · 2023Article
- Tetrahydrobiopterin (BHBiomedicines · 2022Article
- Metformin in cardiovascular diabetology: a focused review of its impact on endothelial function.Theranostics · 2021Review
- Transcriptome-Based Network Analysis Reveals Hirudin Potentiates Anti-Renal Fibrosis Efficacy in UUO Rats.Frontiers in pharmacology · 2021Article
- A hybrid approach reveals the allosteric regulation of GTP cyclohydrolase I.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Glomerular Endothelial Cells as Instigators of Glomerular Sclerotic Diseases.Frontiers in pharmacology · 2020Review
- Endothelial cell-specific overexpression of endothelial nitric oxide synthase in Ins2Akita mice exacerbates diabetic nephropathy.Journal of diabetes and its complications · 2019Article
- The Warburg Effect in Diabetic Kidney Disease.Seminars in nephrology · 2018Review
- Cinacalcet-mediated activation of the CaMKKβ-LKB1-AMPK pathway attenuates diabetic nephropathy in db/db mice by modulation of apoptosis and autophagy.Cell death & disease · 2018Article
- Glomerular Endothelial Cell Stress and Cross-Talk With Podocytes in Early [corrected] Diabetic Kidney Disease.Frontiers in medicine · 2018Review
- Klotho attenuates renal hypertrophy and glomerular injury in Ins2Akita diabetic mice.Clinical and experimental nephrology · 2016Article
- Mass Spectrometry Imaging Reveals Elevated Glomerular ATP/AMP in Diabetes/obesity and Identifies Sphingomyelin as a Possible Mediator.EBioMedicine · 2016Article
- Nitric oxide in the normal kidney and in patients with diabetic nephropathy.Journal of nephrology · 2015Review
- Glomerular endothelial cell injury and cross talk in diabetic kidney disease.American journal of physiology. Renal physiology · 2015Review
- The altered renal and hepatic expression of solute carrier transporters (SLCs) in type 1 diabetic mice.PloS one · 2015Article
- Principles of targeting endothelial cell metabolism to treat angiogenesis and endothelial cell dysfunction in disease.EMBO molecular medicine · 2014Review
- The role of the glomerular endothelium in albumin handling.Nature reviews. Nephrology · 2013Review
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 3 countries.
Funding
Abstract
In diabetes, endothelial nitric oxide synthase (eNOS) produces superoxide anion rather than nitric oxide, referred to as "eNOS uncoupling," which may contribute to endothelial dysfunction, albuminuria, and diabetic nephropathy. Reduced levels of endothelium-derived tetrahydrobiopterin (BH4), an essential cofactor for eNOS, promote eNOS uncoupling. Accelerated degradation of guanosine triphosphate cyclohydrolase I (GTPCH I), the rate-limiting enzyme in BH4 biosynthesis, also occurs in diabetes, suggesting that GTPCH I may have a role in diabetic microvascular disease. Here, we crossed endothelium-dominant GTPCH I transgenic mice with Ins2(+/Akita) diabetic mice and found that endothelial overexpression of GTPCH I led to higher levels of intrarenal BH4 and lower levels of urinary albumin and reactive oxygen species compared with diabetic control mice. Furthermore, GTPCH I overexpression attenuated the hyperpermeability of macromolecules observed in diabetic control mice. In addition, we treated Ins2(+/Akita) mice with metformin, which activates AMP-activated protein kinase (AMPK) and thereby slows the degradation of GTPCH I; despite blood glucose levels that were similar to untreated mice, those treated with metformin had significantly less albuminuria. Similarly, in vitro, treating human glomerular endothelial cells with AMPK activators attenuated glucose-induced reductions in phospho-AMPK, GTPCH I, and coupled eNOS. Taken together, these data suggest that maintenance of endothelial GTPCH I expression and the resulting improvement in BH4 biosynthesis ameliorate diabetic nephropathy.
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