ArticleThe Journal of clinical investigation2016
Urea impairs β cell glycolysis and insulin secretion in chronic kidney disease.
Article in The Journal of clinical investigation, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 84 papers.
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Who cites it
84 citing papers in PubMed, 161 citations in OpenAlex.
- Trial
- Association of blood urea nitrogen to high-density lipoprotein ratio with all-cause and cardiovascular mortality in individuals with mildly reduced eGFR.Clinics (Sao Paulo, Brazil) · 2026Article
- Blood urea nitrogen to serum albumin ratio, systemic inflammation response index and diabetic macrovascular complications in Chinese inpatients: a cross-sectional analysis.Journal of health, population, and nutrition · 2026Article
- Association Between Impaired Fasting Glucose and Adverse Outcomes in Patients Treated With Peritoneal Dialysis: A Retrospective Study From Southern China.Endocrinology, diabetes & metabolism · 2026Observational
- Liver-pancreas communication in disease and drug development.Acta pharmaceutica Sinica. B · 2026Review
- Urea, TMAO, betaine and other osmolytes as endogenous diuretics in heart failure and hypertension.Heart failure reviews · 2025Review
- Probiotics restore enteric HDL3 secretion and improve prognosis in patients with end-stage renal disease.iMeta · 2025Article
- Cetobacterium somerae-derived argininosuccinic acid promotes intestinal and liver ureagenesis to alleviate ammonia intoxication.Microbiome · 2025Article
- Measurement of Insulin Resistance in Cats With Chronic Kidney Disease.Veterinary medicine and science · 2025Article
- Analysis of patient characteristics and safety of insulin glargine U300 use in 21 359 patients with type-2 diabetes and chronic kidney disease: DPV registry study.Diabetes, obesity & metabolism · 2025Article
- Increased blood urea nitrogen levels and compromised peripheral nerve function in patients with type 2 diabetes.World journal of diabetes · 2025Article
- Integrating the new pharmacological standard of care with traditional nutritional interventions in non-dialysis CKD.Journal of nephrology · 2025Review
- Prediction of First-Onset Cerebral Infarction Risk in Patients with Acute Myocardial Infarction: A Retrospective Cohort Study.International journal of general medicine · 2025Article
- Association between blood urea nitrogen to albumin ratio and diabetic retinopathy: insights from the US National Health and Nutrition Examination Survey.International journal of ophthalmology · 2025Article
- Association Between Blood Urea Nitrogen/Albumin and the Incidence as Well as Progression of Type 2 Diabetes.Nutrients · 2024Article
- Risk factors and prediction model for acute ischemic stroke after off-pump coronary artery bypass grafting based on Bayesian network.BMC medical informatics and decision making · 2024Article
- Interaction of proteinuria and diabetes on the risk of cardiovascular events: a prospective cohort CKD-ROUTE study.BMC public health · 2024Article
- Serum urea concentration and risk of 16 site-specific cancers, overall cancer, and cancer mortality in individuals with metabolic syndrome: a cohort study.BMC medicine · 2024Article
- Challenges of Glycemic Control in People With Diabetes and Advanced Kidney Disease and the Potential of Automated Insulin Delivery.Journal of diabetes science and technology · 2024Review
- Drugs with a negative impact on cognitive functions (part 3): antibacterial agents in patients with chronic kidney disease.Clinical kidney journal · 2024Review
24 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
Abstract
Disorders of glucose homeostasis are common in chronic kidney disease (CKD) and are associated with increased mortality, but the mechanisms of impaired insulin secretion in this disease remain unclear. Here, we tested the hypothesis that defective insulin secretion in CKD is caused by a direct effect of urea on pancreatic β cells. In a murine model in which CKD is induced by 5/6 nephrectomy (CKD mice), we observed defects in glucose-stimulated insulin secretion in vivo and in isolated islets. Similarly, insulin secretion was impaired in normal mouse and human islets that were cultured with disease-relevant concentrations of urea and in islets from normal mice treated orally with urea for 3 weeks. In CKD mouse islets as well as urea-exposed normal islets, we observed an increase in oxidative stress and protein O-GlcNAcylation. Protein O-GlcNAcylation was also observed in pancreatic sections from CKD patients. Impairment of insulin secretion in both CKD mouse and urea-exposed islets was associated with reduced glucose utilization and activity of phosphofructokinase 1 (PFK-1), which could be reversed by inhibiting O-GlcNAcylation. Inhibition of O-GlcNAcylation also restored insulin secretion in both mouse models. These results suggest that insulin secretory defects associated with CKD arise from elevated circulating levels of urea that increase islet protein O-GlcNAcylation and impair glycolysis.
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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 OpenQuestion graph.