ArticleDiabetes2011
Elevated glucose represses liver glucokinase and induces its regulatory protein to safeguard hepatic phosphate homeostasis.
Article in Diabetes, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 67 citations in OpenAlex.
- Factors influencing the initial glycemic efficacy of dorzagliatin, a novel glucokinase activator, in type 2 diabetes.Endocrine · 2025Article
- Conserved glucokinase regulation in zebrafish confirms therapeutic utility for pharmacologic modulation in diabetes.Communications biology · 2024Article
- Precision-cut liver slices as an ex vivo model to assess impaired hepatic glucose production.Communications biology · 2024Article
- Nuclear receptor corepressors non-canonically drive glucocorticoid receptor-dependent activation of hepatic gluconeogenesis.Nature metabolism · 2024Article
- Comprehensive genetic study of the insulin resistance marker TG:HDL-C in the UK Biobank.Nature genetics · 2024Article
- ChREBP is activated by reductive stress and mediates GCKR-associated metabolic traits.Cell metabolism · 2024Article
- The GCKR-P446L gene variant predisposes to raised blood cholesterol and lower blood glucose in the P446L mouse-a model for GCKR rs1260326.Molecular metabolism · 2023Article
- Autologous blood transfusion impedes glycolysis in macrophages to inhibit red blood cell injury in type 2 diabetes through PI3K/Akt/PKM2 signaling axis.Acta diabetologica · 2023Article
- Hexokinase-linked glycolytic overload and unscheduled glycolysis in hyperglycemia-induced pathogenesis of insulin resistance, beta-cell glucotoxicity, and diabetic vascular complications.Frontiers in endocrinology · 2023Article
- Article
- Association between glucokinase regulator gene polymorphisms and serum uric acid levels in Taiwanese adolescents.Scientific reports · 2022Article
- Article
- Synthesis, predictions of drug-likeness, and pharmacokinetic properties of some chiral thioureas as potent enzyme inhibition agents.Turkish journal of chemistry · 2022Article
- Genetic and Metabolic Determinants of Plasma Levels of ANGPTL8.The Journal of clinical endocrinology and metabolism · 2021Article
- The Metformin Mechanism on Gluconeogenesis and AMPK Activation: The Metabolite Perspective.International journal of molecular sciences · 2020Review
- Review
- Metformin lowers glucose 6-phosphate in hepatocytes by activation of glycolysis downstream of glucose phosphorylation.The Journal of biological chemistry · 2020Article
- The Protective Role of the Carbohydrate Response Element Binding Protein in the Liver: The Metabolite Perspective.Frontiers in endocrinology · 2020Review
- Low metformin causes a more oxidized mitochondrial NADH/NAD redox state in hepatocytes and inhibits gluconeogenesis by a redox-independent mechanism.The Journal of biological chemistry · 2019Article
- Functional Variant in the GCKR Gene Affects Lactate Levels Differentially in the Fasting State and During Hyperglycemia.Scientific reports · 2018Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 3 countries.
Funding
Abstract
objectiveThe induction of hepatic glucose 6-phosphatase (G6pc) by glucose presents a paradox of glucose-induced glucose intolerance. We tested whether glucose regulation of liver gene expression is geared toward intracellular homeostasis. RESEARCH DESIGN AND
methodsThe effect of glucose-induced accumulation of phosphorylated intermediates on expression of glucokinase (Gck) and its regulator Gckr was determined in hepatocytes. Cell ATP and uric acid production were measured as indices of cell phosphate homeostasis.
resultsAccumulation of phosphorylated intermediates in hepatocytes incubated at elevated glucose induced rapid and inverse changes in Gck (repression) and Gckr (induction) mRNA concomitantly with induction of G6pc, but had slower effects on the Gckr-to-Gck protein ratio. Dynamic metabolic labeling in mice and liver proteome analysis confirmed that Gckr and Gck are low-turnover proteins. Involvement of Max-like protein X in glucose-mediated Gck-repression was confirmed by chromatin immunoprecipitation analysis. Elevation of the Gck-to-Gckr ratio in hepatocytes was associated with glucose-dependent ATP depletion and elevated urate production confirming compromised phosphate homeostasis.
conclusionsThe lowering by glucose of the Gck-to-Gckr ratio provides a potential explanation for the impaired hepatic glucose uptake in diabetes. Elevated uric acid production at an elevated Gck-to-Gckr ratio supports a role for glucose regulation of gene expression in hepatic phosphate homeostasis.
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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.