ArticleThe Biochemical journal2000
Impaired nitric oxide production in coronary endothelial cells of the spontaneously diabetic BB rat is due to tetrahydrobiopterin deficiency.
Article in The Biochemical journal, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers.
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Who cites it
69 citing papers in PubMed, 177 citations in OpenAlex.
- The Effects of Nitrate on Brown Fat Fraction and Activation in Older Adults With Type 2 Diabetes: A Randomised, Double-Blind and Placebo-Controlled Crossover Trial.European journal of sport science · 2026Trial
- Pharmacologic and pharmacokinetic profile of repifermin (KGF-2) in monkeys and comparative pharmacokinetics in humans.AAPS pharmSci · 2002Trial
- The status of studies on the mechanism of microcirculatory dysfunction in the process of diabetic kidney injury.Diabetology & metabolic syndrome · 2025Review
- Preliminary screening of biomarkers and drug candidates in a mouse model of β-thalassemia based on quasi-targeted metabolomics.Frontiers in physiology · 2024Article
- Different effects of medications for hypertension on renal function between patients with and without diabetes mellitus undergoing percutaneous coronary intervention: a retrospective single-center cohort study.BMC cardiovascular disorders · 2023Article
- Endothelial dysfunction due to eNOS uncoupling: molecular mechanisms as potential therapeutic targets.Cellular & molecular biology letters · 2023Article
- Dietary supplementation with 0.4% L-arginine between days 14 and 30 of gestation enhances NO and polyamine syntheses and water transport in porcine placentae.Journal of animal science and biotechnology · 2022Article
- Naringenin upregulates GTPCH1/eNOS to ameliorate high glucose-induced retinal endothelial cell injury.Experimental and therapeutic medicine · 2022Article
- Hydroxyproline in animal metabolism, nutrition, and cell signaling.Amino acids · 2022Review
- Oxidative Stress, GTPCH1, and Endothelial Nitric Oxide Synthase Uncoupling in Hypertension.Antioxidants & redox signaling · 2021Review
- 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
- The effect of hyperglycemia on neurovascular coupling and cerebrovascular patterning in zebrafish.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2020Article
- Vascular endothelial dysfunction, a major mediator in diabetic cardiomyopathy.Acta pharmacologica Sinica · 2019Review
- Specialized Pro-resolving Lipid Mediators: Modulation of Diabetes-Associated Cardio-, Reno-, and Retino-Vascular Complications.Frontiers in pharmacology · 2018Review
- Tetrahydrobiopterin activates brown adipose tissue and regulates systemic energy metabolism.JCI insight · 2017Article
- Effects of Diabetes on Salivary Gland Protein Expression of Tetrahydrobiopterin and Nitric Oxide Synthesis and Function.Journal of periodontology · 2016Article
- Mildly compromised tetrahydrobiopterin cofactor biosynthesis due to Pts variants leads to unusual body fat distribution and abdominal obesity in mice.Journal of inherited metabolic disease · 2016Article
- M2 Macrophage Polarization Mediates Anti-inflammatory Effects of Endothelial Nitric Oxide Signaling.Diabetes · 2015Article
- Erythropoietin prevents endothelial dysfunction in GTP-cyclohydrolase I-deficient hph1 mice.Journal of cardiovascular pharmacology · 2014Article
- Regulation of obesity and insulin resistance by nitric oxide.Free radical biology & medicine · 2014Review
9 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Endothelial cells (EC) from diabetic BioBreeding (BB) rats have an impaired ability to produce NO. This deficiency is not due to a defect in the constitutive isoform of NO synthase in EC (ecNOS) or alterations in intracellular calcium, calmodulin, NADPH or arginine levels. Instead, ecNOS cannot produce sufficient NO because of a deficiency in tetrahydrobiopterin (BH(4)), a cofactor necessary for enzyme activity. EC from diabetic rats exhibited only 12% of the BH(4) levels found in EC from normal animals or diabetes-prone animals which did not develop disease. As a result, NO synthesis by EC of diabetic rats was only 18% of that for normal animals. Increasing BH(4) levels with sepiapterin increased NO production, suggesting that BH(4) deficiency is a metabolic basis for impaired endothelial NO synthesis in diabetic BB rats. This deficiency is due to decreased activity of GTP-cyclohydrolase I, the first and rate-limiting enzyme in the de novo biosynthesis of BH(4). GTP-cyclohydrolase activity was low because of a decreased expression of the protein in the diabetic cells.
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