ArticleDiabetes2012
Glucotoxicity induces glucose-6-phosphatase catalytic unit expression by acting on the interaction of HIF-1α with CREB-binding protein.
Article in Diabetes, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 47 citations in OpenAlex.
- Crosstalk between the aryl hydrocarbon receptor and hypoxia-inducible factor 1α pathways in human islet models.Islets · 2025Article
- Identifying G6PC3 as a Potential Key Molecule in Hypoxic Glucose Metabolism of Glioblastoma Derived from the Depiction ofBioMed research international · 2024Article
- MiR-494 induces metabolic changes through G6pc targeting and modulates sorafenib response in hepatocellular carcinoma.Journal of experimental & clinical cancer research : CR · 2023Article
- Effects of Amino Acids Supplementation on Lipid and Glucose Metabolism in HepG2 Cells.Nutrients · 2022Article
- Pomegranate peel anthocyanins prevent diet-induced obesity and insulin resistance in association with modulation of the gut microbiota in mice.European journal of nutrition · 2022Article
- Crosstalk of hepatocyte nuclear factor 4a and glucocorticoid receptor in the regulation of lipid metabolism in mice fed a high-fat-high-sugar diet.Lipids in health and disease · 2022Article
- The transcriptional corepressor CtBP2 serves as a metabolite sensor orchestrating hepatic glucose and lipid homeostasis.Nature communications · 2021Article
- Glucose-6-phosphatase Expression-Mediated [Molecular imaging and biology · 2019Article
- Experimental Applications ofMolecules and cells · 2019Article
- Differential Impact of Flavonoids on Redox Modulation, Bioenergetics, and Cell Signaling in Normal and Tumor Cells: A Comprehensive Review.Antioxidants & redox signaling · 2018Review
- MCU-knockdown attenuates high glucose-induced inflammation through regulating MAPKs/NF-κB pathways and ROS production in HepG2 cells.PloS one · 2018Article
- Exposure to an acute hypoxic stimulus during early life affects the expression of glucose metabolism-related genes at first-feeding in trout.Scientific reports · 2017Article
- The brain metabolic activity after resuscitation with liposome-encapsulated hemoglobin in a rat model of hypovolemic shock.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2015Article
- Glucose-6-phosphatase is a key metabolic regulator of glioblastoma invasion.Molecular cancer research : MCR · 2014Article
- Impaired hypoxia-inducible factor (HIF) regulation by hyperglycemia.Journal of molecular medicine (Berlin, Germany) · 2014Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The activation of glucose-6-phosphatase (G6Pase), a key enzyme of endogenous glucose production, is correlated with type 2 diabetes. Type 2 diabetes is characterized by sustained hyperglycemia leading to glucotoxicity. We investigated whether glucotoxicity mechanisms control the expression of the G6Pase catalytic unit (G6pc). We deciphered the transcriptional regulatory mechanisms of the G6pc promoter by glucotoxicity in a hepatoma cell line then in primary hepatocytes and in the liver of diabetic mice. High glucose exposure induced the production of reactive oxygen species (ROS) and, in parallel, induced G6pc promoter activity. In hepatocytes, glucose induced G6pc gene expression and glucose release. The decrease of ROS concentrations by antioxidants eliminated all the glucose-inductive effects. The induction of G6pc promoter activity by glucose was eliminated in the presence of small interfering RNA, targeting either the hypoxia-inducible factor (HIF)-1α or the CREB-binding protein (CBP). Glucose increased the interaction of HIF-1α with CBP and the recruitment of HIF-1 on the G6pc promoter. The same mechanism might occur in hyperglycemic mice. We deciphered a new regulatory mechanism induced by glucotoxicity. This mechanism leading to the induction of HIF-1 transcriptional activity may contribute to the increase of hepatic glucose production during type 2 diabetes.
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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.