ArticlePloS one2010
Hypoxia promotes glycogen accumulation through hypoxia inducible factor (HIF)-mediated induction of glycogen synthase 1.
Article in PloS one, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 131 papers.
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Who cites it
131 citing papers in PubMed, 274 citations in OpenAlex.
- Trial
- Alpha-ketoglutarate enhances adipose-derived stem cells survival in wound healing by hypoxia-inducible factor 1-alpha-mediated redox homeostasis and glycogen-dependent bioenergetics.World journal of stem cells · 2026Article
- Nanoplatform-Mediated Remodeling of the Immune Microenvironment in Renal Cell Carcinoma.International journal of nanomedicine · 2026Review
- Exercise modality-dependent mitochondrial respiratory capacity in satellite cells and conditioned serum-induced responses in cultured myotubes.Experimental physiology · 2026Article
- INHAND: Non-proliferative and proliferative lesions of fish - Chapter 6. Fish hepatobiliary.Journal of toxicologic pathology · 2026Article
- Catabolic rewiring in cancer impacts dietary interventions.Communications biology · 2025Review
- Role of oxygen sensing and hypoxia-inducible factors in orchestrating innate immune responses.Nature immunology · 2025Review
- Disulfidptosis mechanisms and therapeutic implications in cancer metabolic reprogramming and future perspectives.Discover oncology · 2025Review
- Combined effects of mechanical overload and high-intensity interval training on skeletal muscle hypertrophy in male mice.Physiological reports · 2025Article
- TSG6 affects anti cancer drug resistance and angiogenesis in 3D spheroid model of canine mammary gland tumor cells.Scientific reports · 2025Article
- Oxidative Stress and Inflammation in Hypoxemic Respiratory Diseases and Their Comorbidities: Molecular Insights and Diagnostic Advances in Chronic Obstructive Pulmonary Disease and Sleep Apnea.Antioxidants (Basel, Switzerland) · 2025Review
- Identification and characterization of microRNAs in the liver of yak (Bos grunniens) associated with energy deficiency at high-altitude.Animal bioscience · 2025Article
- Unveiling GBE1 as a hypoxia-related prognostic gene with significant impact on immune cell infiltration in HER2-enriched breast cancer.Discover oncology · 2025Article
- Glycogen synthase is required for heat shock-mediated autophagy induction in neuronal cells.Biology open · 2025Article
- Cardiomyocytes in Hypoxia: Cellular Responses and Implications for Cell-Based Cardiac Regenerative Therapies.Bioengineering (Basel, Switzerland) · 2025Review
- Differential expression of HIF-1α and its hypoxia-related inducers in the spleens of plateau yaks and plain yellow cattle.Histology and histopathology · 2025Article
- Hypoxia and activation of hypoxia inducible factor alpha as influencers of inflammatory helper T cells in autoimmune disease - a link between cancer and autoimmunity.Frontiers in immunology · 2025Review
- Whole-genome sequencing of copy number variation analysis in Ethiopian cattle reveals adaptations to diverse environments.BMC genomics · 2024Article
- Hypoxia-Induced Differences in the Expression of Pyruvate Dehydrogenase Kinase 1-Related Factors in the Renal Tissues and Renal Interstitial Fibroblast-like Cells of Yak (Bos Grunniens).Animals : an open access journal from MDPI · 2024Article
- Advancing Human iPSC-Derived Cardiomyocyte Hypoxia Resistance for Cardiac Regenerative Therapies through a Systematic Assessment of In Vitro Conditioning.International journal of molecular sciences · 2024Article
71 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
13 authors at 6 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
When oxygen becomes limiting, cells reduce mitochondrial respiration and increase ATP production through anaerobic fermentation of glucose. The Hypoxia Inducible Factors (HIFs) play a key role in this metabolic shift by regulating the transcription of key enzymes of glucose metabolism. Here we show that oxygen regulates the expression of the muscle glycogen synthase (GYS1). Hypoxic GYS1 induction requires HIF activity and a Hypoxia Response Element within its promoter. GYS1 gene induction correlated with a significant increase in glycogen synthase activity and glycogen accumulation in cells exposed to hypoxia. Significantly, knockdown of either HIF1alpha or GYS1 attenuated hypoxia-induced glycogen accumulation, while GYS1 overexpression was sufficient to mimic this effect. Altogether, these results indicate that GYS1 regulation by HIF plays a central role in the hypoxic accumulation of glycogen. Importantly, we found that hypoxia also upregulates the expression of UTP:glucose-1-phosphate urydylyltransferase (UGP2) and 1,4-alpha glucan branching enzyme (GBE1), two enzymes involved in the biosynthesis of glycogen. Therefore, hypoxia regulates almost all the enzymes involved in glycogen metabolism in a coordinated fashion, leading to its accumulation. Finally, we demonstrated that abrogation of glycogen synthesis, by knock-down of GYS1 expression, impairs hypoxic preconditioning, suggesting a physiological role for the glycogen accumulated during chronic hypoxia. In summary, our results uncover a novel effect of hypoxia on glucose metabolism, further supporting the central importance of metabolic reprogramming in the cellular adaptation to hypoxia.
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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.