ArticleAmerican journal of physiology. Renal physiology2014
Diabetic nephropathy is resistant to oral L-arginine or L-citrulline supplementation.
Article in American journal of physiology. Renal physiology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 36 citations in OpenAlex.
- L-Citrulline: Novel Pharmacotherapy to Improve Outcomes in Infants and Children at Risk of Systemic or Pulmonary Vascular Disease.Pharmaceuticals (Basel, Switzerland) · 2026Review
- ERRα-NOS2-mediated citrulline metabolism attenuates tubular epithelial cell senescence in diabetic kidney disease.Redox biology · 2026Article
- Diabetic nephropathy: Role of nitric oxide.Nitric oxide : biology and chemistry · 2025Review
- Sex- and Dose-Dependent Effect of L-Citrulline on Body Weight and Food Intake in Obese Type 2 Diabetic Rats.International journal of endocrinology and metabolism · 2025Article
- Identification of potential biomarkers for diabetic nephropathy via UPLC-MS/MS-based metabolomics.Frontiers in endocrinology · 2025Article
- Article
- Molecular mechanisms underlying the role of hypoxia-inducible factor-1 α in metabolic reprogramming in renal fibrosis.Frontiers in endocrinology · 2022Review
- Watermelon and L-Citrulline in Cardio-Metabolic Health: Review of the Evidence 2000-2020.Current atherosclerosis reports · 2021Review
- Homoarginine ameliorates diabetic nephropathy independent of nitric oxide synthase-3.Physiological reports · 2021Article
- Selective inhibition of arginase-2 in endothelial cells but not proximal tubules reduces renal fibrosis.JCI insight · 2020Article
- Enhancing kidney DDAH-1 expression by adenovirus delivery reduces ADMA and ameliorates diabetic nephropathy.American journal of physiology. Renal physiology · 2020Article
- Detrimental Effects of Chronic L-Arginine Rich Food on Aging Kidney.Frontiers in pharmacology · 2020Article
- Review
- l-Homoarginine supplementation prevents diabetic kidney damage.Physiological reports · 2019Article
- Analysis of serum metabolomics among biopsy-proven diabetic nephropathy, type 2 diabetes mellitus and healthy controls.RSC advances · 2019Article
- Iron Overload Damages the Endothelial MitochondriaOxidative medicine and cellular longevity · 2019Article
- Arginase: A Multifaceted Enzyme Important in Health and Disease.Physiological reviews · 2018Review
- Distinct roles of arginases 1 and 2 in diabetic nephropathy.American journal of physiology. Renal physiology · 2017Article
- Ablation of Arginase II Spares Arginine and Abolishes the Arginine Requirement for Growth in Male Mice.The Journal of nutrition · 2017Article
- Arginase-2 mediates renal ischemia-reperfusion injury.American journal of physiology. Renal physiology · 2017Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Our recent publication showed that pharmacological blockade of arginases confers kidney protection in diabetic nephropathy via a nitric oxide (NO) synthase (NOS)3-dependent mechanism. Arginase competes with endothelial NOS (eNOS) for the common substrate L-arginine. Lack of L-arginine results in reduced NO production and eNOS uncoupling, which lead to endothelial dysfunction. Therefore, we hypothesized that L-arginine or L-citrulline supplementation would ameliorate diabetic nephropathy. DBA mice injected with multiple low doses of vehicle or streptozotocin (50 mg/kg ip for 5 days) were provided drinking water with or without L-arginine (1.5%, 6.05 g·kg(-1)·day(-1)) or L-citrulline (1.66%, 5.73 g·kg(-1)·day(-1)) for 9 wk. Nonsupplemented diabetic mice showed significant increases in albuminuria, blood urea nitrogen, glomerular histopathological changes, kidney macrophage recruitment, kidney TNF-α and fibronectin mRNA expression, kidney arginase activity, kidney arginase-2 protein expression, and urinary oxidative stress along with a significant reduction of nephrin and eNOS protein expression and kidney nitrite + nitrate compared with normal mice after 9 wk of diabetes. Surprisingly, L-arginine or L-citrulline supplementation in diabetic mice did not affect any of these parameters despite greatly increasing kidney and plasma arginine levels. These findings demonstrate that chronic L-arginine or L-citrulline supplementation does not prevent or reduce renal injury in a model of type 1 diabetes.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.