ArticlePloS one2013
Hyperuricemia causes pancreatic β-cell death and dysfunction through NF-κB signaling pathway.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers, 1 of them a synthesis that pooled it.
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Who cites it
52 citing papers in PubMed, 1 synthesis or guideline pooled it, 105 citations in OpenAlex.
- Uric acid lowering improves insulin sensitivity and lowers blood pressure: a meta-analysis of randomized parallel-controlled clinical trials.African health sciences · 2021Pooled it
- Consumption of sucrose-sweetened soft drinks increases plasma levels of uric acid in overweight and obese subjects: a 6-month randomised controlled trial.European journal of clinical nutrition · 2015Trial
- Neuregulin 4-dependent MAPK amplification mediates urate-induced β-cell dysfunction.Journal of diabetes investigation · 2026Article
- Serum Uric Acid as a Biomarker for Incident Type 2 Diabetes Mellitus: A 6-Year Cohort Study in Qatar.Metabolites · 2026Article
- A positive linear association between uric acid and the risk of gestational diabetes mellitus: a single-center retrospective study.Frontiers in endocrinology · 2026Article
- Diabetes mediates the association between uric acid to high-density lipoprotein cholesterol ratio and abdominal aortic calcification: a cross-sectional study.Scientific reports · 2025Article
- ZHX3 interacts with CEBPB to repress hepatic gluconeogenic gene expression and uric acid secretion.PNAS nexus · 2025Article
- CRISPR/Cas9 Mediated Deletion of the Uox Gene Generates a Mouse Model of Hyperuricemia with Multiple Complications.Journal of cardiovascular translational research · 2024Article
- Association of serum uric acid with hypertriglyceridemia in children and adolescents: a cross-sectional study.Lipids in health and disease · 2024Article
- Serum Uric Acid Associates with Systemic Complement C3 Activation in Severe ANCA-Associated Renal Vasculitides.International journal of molecular sciences · 2024Article
- Insufficient compensatory pancreatic β-cells function might be closely associated with hyperuricemia in U.S. adults: evidence from the National Health and Nutrition Examination Survey.BMC public health · 2024Article
- Rational design of a genome-based insulated system inBioengineering & translational medicine · 2023Article
- The Management of Diabetes with Hyperuricemia: Can We Hit Two Birds with One Stone?Journal of inflammation research · 2023Review
- Serum uric acid and risk of diabetic neuropathy: a genetic correlation and mendelian randomization study.Frontiers in endocrinology · 2023Article
- Prevalence and associated factors of hyperuricemia among Chinese patients with diabetes: a cross-sectional study.Therapeutic advances in endocrinology and metabolism · 2023Article
- Serum uric acid/creatinine ratio and free androgen index are synergistically associated with increased risk of polycystic ovary syndrome in obese women.BMC endocrine disorders · 2022Article
- The Influence of Serum Uric Acid on the Brain and Cognitive Dysfunction.Frontiers in psychiatry · 2022Review
- The protective role of serum uric acid against premature membrane rupture in gestational diabetes: a cross-sectional study.BMC endocrine disorders · 2021Article
- Lower threshold to NFκB activity sensitizes murine β-cells to streptozotocin.The Journal of endocrinology · 2021Article
- Uric acid-induced pancreatic β-cell dysfunction.BMC endocrine disorders · 2021Review
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Accumulating clinical evidence suggests that hyperuricemia is associated with an increased risk of type 2 diabetes. However, it is still unclear whether elevated levels of uric acid can cause direct injury of pancreatic β-cells. In this study, we examined the effects of uric acid on β-cell viability and function. Uric acid solution or normal saline was administered intraperitoneally to mice daily for 4 weeks. Uric acid-treated mice exhibited significantly impaired glucose tolerance and lower insulin levels in response to glucose challenge than did control mice. However, there were no significant differences in insulin sensitivity between the two groups. In comparison to the islets in control mice, the islets in the uric acid-treated mice were markedly smaller in size and contained less insulin. Treatment of β-cells in vitro with uric acid activated the NF-κB signaling pathway through IκBα phosphorylation, resulting in upregulated inducible nitric oxide synthase (iNOS) expression and excessive nitric oxide (NO) production. Uric acid treatment also increased apoptosis and downregulated Bcl-2 expression in Min6 cells. In addition, a reduction in insulin secretion under glucose challenge was observed in the uric acid-treated mouse islets. These deleterious effects of uric acid on pancreatic β-cells were attenuated by benzbromarone, an inhibitor of uric acid transporters, NOS inhibitor L-NMMA, and Bay 11-7082, an NF-κB inhibitor. Further investigation indicated that uric acid suppressed levels of MafA protein through enhancing its degradation. Collectively, our data suggested that an elevated level of uric acid causes β-cell injury via the NF-κB-iNOS-NO signaling axis.
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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.