ArticleDiabetes2013
Glucose-6-phosphate-mediated activation of liver glycogen synthase plays a key role in hepatic glycogen synthesis.
Article in Diabetes, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
55 citing papers in PubMed, 105 citations in OpenAlex.
- Acute AKT signaling increases glucose phosphorylation and contribution to glycogen in hepatocytes.iScience · 2026Article
- Metabolic and Signaling Dysregulation in a Cellular Model of Hepatic Insulin Resistance.Current issues in molecular biology · 2026Article
- Structures of human glucose-6-phosphate transporter reveal reciprocal antiport mechanism driving glucose-6-phosphate and inorganic phosphate exchange.Nature communications · 2025Article
- Hepatocyte Piezo1 regulates glycogen metabolism via the FGF21-STAT3 pathway.Cellular and molecular life sciences : CMLS · 2025Article
- Molecular mechanisms of metabolic dysfunction-associated steatotic liver disease (MASLD): functional analysis of glucose and fructose metabolism pathways.Clinical science (London, England : 1979) · 2025Review
- Article
- Effects of Dietary Rumen-Protected Glucose and Rumen-Protected Taurine Levels on Growth Performance, Serum Biochemical Indicators, and Liver Health in Yaks.Animals : an open access journal from MDPI · 2025Article
- Integrative analysis of the 3D genome and epigenome in mouse embryonic tissues.Nature structural & molecular biology · 2025Article
- Intergenerational metabolic toxicity of perfluorooctanesulfonic acid exposure in adult offspring rats: a multi-omics approach.Frontiers in endocrinology · 2025Article
- Duration of morning hyperinsulinemia determines hepatic glucose uptake and glycogen storage later in the day.American journal of physiology. Endocrinology and metabolism · 2024Article
- Time and dose selective glucose metabolism for glucose homeostasis and energy conversion in the liver.NPJ systems biology and applications · 2024Article
- Duration of Morning Hyperinsulinemia Determines Hepatic Glucose Uptake and Glycogen Storage Later in the Day.bioRxiv : the preprint server for biology · 2024Article
- Integration of metabolic flux with hepatic glucagon signaling and gene expression profiles in the conscious dog.American journal of physiology. Endocrinology and metabolism · 2024Article
- The Role of Acyl-CoA Synthetase 1 in Bioactive Lipid Accumulation and the Development of Hepatic Insulin Resistance.Nutrients · 2024Article
- Trans-omic analysis reveals opposite metabolic dysregulation between feeding and fasting in liver associated with obesity.iScience · 2024Article
- mTORC1 controls murine postprandial hepatic glycogen synthesis via Ppp1r3b.The Journal of clinical investigation · 2024Article
- Revving the engine: PKB/AKT as a key regulator of cellular glucose metabolism.Frontiers in physiology · 2023Review
- 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
- Mechanism of glycogen synthase inactivation and interaction with glycogenin.Nature communications · 2022Article
- Hepatic Mitochondrial Dysfunction and Risk of Liver Disease in an Ovine Model of "PCOS Males".Biomedicines · 2022Article
Corrections and comments
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Authors and funding
15 authors at 4 institutions in 2 countries.
Funding
Abstract
The liver responds to an increase in blood glucose levels in the postprandial state by uptake of glucose and conversion to glycogen. Liver glycogen synthase (GYS2), a key enzyme in glycogen synthesis, is controlled by a complex interplay between the allosteric activator glucose-6-phosphate (G6P) and reversible phosphorylation through glycogen synthase kinase-3 and the glycogen-associated form of protein phosphatase 1. Here, we initially performed mutagenesis analysis and identified a key residue (Arg(582)) required for activation of GYS2 by G6P. We then used GYS2 Arg(582)Ala knockin (+/R582A) mice in which G6P-mediated GYS2 activation had been profoundly impaired (60-70%), while sparing regulation through reversible phosphorylation. R582A mutant-expressing hepatocytes showed significantly reduced glycogen synthesis with glucose and insulin or glucokinase activator, which resulted in channeling glucose/G6P toward glycolysis and lipid synthesis. GYS2(+/R582A) mice were modestly glucose intolerant and displayed significantly reduced glycogen accumulation with feeding or glucose load in vivo. These data show that G6P-mediated activation of GYS2 plays a key role in controlling glycogen synthesis and hepatic glucose-G6P flux control and thus whole-body glucose 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.