ArticleNature metabolism2020
Glucose-dependent partitioning of arginine to the urea cycle protects β-cells from inflammation.
Article in Nature metabolism, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers, 2 of them syntheses that pooled it.
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Who cites it
38 citing papers in PubMed, 2 syntheses or guidelines pooled it, 62 citations in OpenAlex.
- Cross-Study Meta-Analysis of Blood Transcriptomes in Type 2 Diabetes.International journal of molecular sciences · 2025Pooled it
- Genetic liability of gut microbiota for idiopathic pulmonary fibrosis and lung function: a two-sample Mendelian randomization study.Frontiers in cellular and infection microbiology · 2024Pooled it
- Associations between arginine metabolism and gestational diabetes mellitus: an exploratory longitudinal study using widely targeted metabolomics.BMC pregnancy and childbirth · 2026Article
- Differential metabolomic prediction of outcomes in HFpEF and HFrEF: a prospective international multi-ethnic cohort study.Cardiovascular research · 2026Article
- Liver-pancreas communication in disease and drug development.Acta pharmaceutica Sinica. B · 2026Review
- Urea cycle modulation by combined SGLT2 inhibitors and metformin.BMC medicine · 2026Article
- [Therapeutic efficacy of ASS1 combined with LOLA in the treatment of hyperammonemia in mice].Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2025Article
- The Physiological Roles and Pathological Implications of Urea Transporters in the Cardiovascular System.Biomedicines · 2025Review
- Cetobacterium somerae-derived argininosuccinic acid promotes intestinal and liver ureagenesis to alleviate ammonia intoxication.Microbiome · 2025Article
- Renalase inhibition defends against acute and chronic β cell stress by regulating cell metabolism.Molecular metabolism · 2025Article
- Pyruvate Carboxylase as a Moonlighting Metabolic Enzyme Protects β-Cell From Senescence.Journal of diabetes · 2025Article
- Temporal dynamics of macrophage transcriptional profiles during zebrafish wound healing.Frontiers in immunology · 2025Article
- Serum Metabolomic Signatures of Dyslipidemia in Narcolepsy Type 1: A Multi-Center Cross-Sectional Study.Nature and science of sleep · 2025Article
- Sepsis-induced changes in pyruvate metabolism: insights and potential therapeutic approaches.EMBO molecular medicine · 2024Review
- The mitochondrial enzyme pyruvate carboxylase restricts pancreatic β-cell senescence by blocking p53 activation.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Glucokinase (GCK) in diabetes: from molecular mechanisms to disease pathogenesis.Cellular & molecular biology letters · 2024Review
- LDHB contributes to the regulation of lactate levels and basal insulin secretion in human pancreatic β cells.Cell reports · 2024Article
- Unraveling the role of the mitochondrial one-carbon pathway in undifferentiated thyroid cancer by multi-omics analyses.Nature communications · 2024Article
- Mitochondrial bioenergetics, metabolism, and beyond in pancreatic β-cells and diabetes.Frontiers in molecular biosciences · 2024Review
- β Cell Stress and Endocrine Function During T1D: What Is Next to Discover?Endocrinology · 2023Article
Corrections and comments
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Authors and funding
22 authors at 7 institutions in 2 countries.
Funding
Abstract
Chronic inflammation is linked to diverse disease processes, but the intrinsic mechanisms that determine cellular sensitivity to inflammation are incompletely understood. Here, we show the contribution of glucose metabolism to inflammation-induced changes in the survival of pancreatic islet β-cells. Using metabolomic, biochemical and functional analyses, we investigate the protective versus non-protective effects of glucose in the presence of pro-inflammatory cytokines. When protective, glucose metabolism augments anaplerotic input into the TCA cycle via pyruvate carboxylase (PC) activity, leading to increased aspartate levels. This metabolic mechanism supports the argininosuccinate shunt, which fuels ureagenesis from arginine and conversely diminishes arginine utilization for production of nitric oxide (NO), a chief mediator of inflammatory cytotoxicity. Activation of the PC-urea cycle axis is sufficient to suppress NO synthesis and shield cells from death in the context of inflammation and other stress paradigms. Overall, these studies uncover a previously unappreciated link between glucose metabolism and arginine-utilizing pathways via PC-directed ureagenesis as a protective mechanism.
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Registered trials
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.