ArticleFrontiers in immunology2022
Hyperuricemia contributes to glucose intolerance of hepatic inflammatory macrophages and impairs the insulin signaling pathway
Article in Frontiers in immunology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 1 of them a synthesis that pooled it.
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Who cites it
24 citing papers in PubMed, 1 synthesis or guideline pooled it, 23 citations in OpenAlex.
- The link between hyperuricemia and diabetes: insights from a quantitative analysis of scientific literature.Frontiers in endocrinology · 2024Pooled it
- Neuregulin 4-dependent MAPK amplification mediates urate-induced β-cell dysfunction.Journal of diabetes investigation · 2026Article
- Review
- Serum uric acid and the trajectory of cardiometabolic multimorbidity: a prospective study conducted with data from the UK Biobank.Nutrition journal · 2026Article
- Clostridium butyricum and its metabolites regulate macrophage polarization through miR-146a to antagonize gouty arthritis.Journal of advanced research · 2026Article
- Retinol Binding Protein 4 and Uric Acid as Risk Factors for Insulin Resistance in Type 2 Diabetes Mellitus.Journal of diabetes research · 2026Article
- Therapeutic potential of traditional Chinese medicine for hyperuricemia: mechanistic insights and clinical prospects.Frontiers in pharmacology · 2026Review
- Association between uric acid and non-alcoholic fatty liver disease in patients with hypertension.PloS one · 2026Article
- Advances in post-translational and epigenetic modification of hyperuricemia-to-gout progression: mechanisms and therapeutic targets.Frontiers in cell and developmental biology · 2026Review
- Comparative associations of immune-inflammatory, immune-lipid, and metabolic composite indices with hyperuricemia among Chinese adults with glycemic abnormalities: a health examination-based cross-sectional study.Frontiers in endocrinology · 2026Observational
- Firsekibart for the Treatment of Gout Complicated by Type 2 Diabetes Mellitus: A Real-World Case Series.Journal of inflammation research · 2026Article
- The interplay between NLRP3 inflammasome and metabolic signals in gouty arthritis.Frontiers in immunology · 2026Review
- Hyperuricemia was associated with metabolic response against brain injury instead of metabolism syndrome in Tibet: a cross-sectional analysis.Frontiers in endocrinology · 2026Article
- The association between the uric acid to high-density lipoprotein cholesterol ratio (UHR) index and obesity in postmenopausal women: a cross-sectional analysis based on the NHANES.Lipids in health and disease · 2025Article
- Triglyceride-glucose Index and Mortality in a Large Regional-based Italian Database (URRAH Project).The Journal of clinical endocrinology and metabolism · 2025Article
- Hyperuricemia-induced complications: dysfunctional macrophages serve as a potential bridge.Frontiers in immunology · 2025Review
- The Role of Beta-Hydroxybutyrate in Mitigating the Inflammatory and Metabolic Consequences of Uric Acid.Metabolites · 2024Article
- Highland Barley Alleviates High-Fat Diet-Induced Obesity and Liver Injury Through the IRS2/PI3K/AKT Signaling Pathway in Rats.Nutrients · 2024Article
- Integrating myocardial metabolic imaging and stress myocardial contrast echocardiography to improve the diagnosis of coronary microvascular diseases in rabbits.Quantitative imaging in medicine and surgery · 2024Article
- Integrin αM promotes macrophage alternative M2 polarization in hyperuricemia-related chronic kidney disease.MedComm · 2024Article
Corrections and comments
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Authors and funding
18 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Aim: Numerous reports have demonstrated the key importance of macrophage-elicited metabolic inflammation in insulin resistance (IR). Our previous studies confirmed that hyperuricemia or high uric acid (HUA) treatment induced an IR state in several peripheral tissues to promote the development of type 2 diabetes mellitus (T2DM). However, the effect of HUA on glucose uptake and the insulin sensitivity of macrophages and its mechanism is unclear. Methods: To assess systemic IR, we generated hyperuricemic mice by urate oxidase knockout (UOX-KO). Then, glucose/insulin tolerance, the tissue uptake of 18F-fluorodeoxyglucose, body composition, and energy balance were assessed. Glucose uptake of circulating infiltrated macrophages in the liver was evaluated by glucose transporter type 4 (GLUT-4) staining. Insulin sensitivity and the insulin signaling pathway of macrophages were demonstrated using the 2-NBDG kit, immunoblotting, and immunofluorescence assays. The immunoprecipitation assay and LC-MS analysis were used to determine insulin receptor substrate 2 (IRS2) levels and its interacting protein enrichment under HUA conditions. Results: Compared to WT mice (10 weeks old), serum uric acid levels were higher in UOX-KO mice (WT, 182.3 ± 5.091 μM versus KO, 421.9 ± 45.47 μM). Hyperuricemic mice with metabolic disorders and systemic IR showed inflammatory macrophage recruitment and increased levels of circulating proinflammatory cytokines. HUA inhibited the nuclear translocation of GLUT-4 in hepatic macrophages, restrained insulin-induced glucose uptake and glucose tolerance, and blocked insulin IRS2/PI3K/AKT signaling. Meanwhile, HUA mediated the IRS2 protein degradation pathway and activated AMPK/mTOR in macrophages. LC-MS analysis showed that ubiquitination degradation could be involved in IRS2 and its interacting proteins to contribute to IR under HUA conditions. Conclusion: The data suggest that HUA-induced glucose intolerance in hepatic macrophages contributed to insulin resistance and impaired the insulin signaling pathway
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