ArticleScientific reports2018
PHD3 regulates glucose metabolism by suppressing stress-induced signalling and optimising gluconeogenesis and insulin signalling in hepatocytes.
Article in Scientific reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.
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Who cites it
17 citing papers in PubMed, 1 synthesis or guideline pooled it, 23 citations in OpenAlex.
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- Dynamic Regulation of HIF1α and Oxygen-Sensing Factors in Cyclic Bovine Corpus Luteum and During LPS Challenge.Animals : an open access journal from MDPI · 2025Article
- miR-34a is a tumor suppressor in zebrafish and its expression levels impact metabolism, hematopoiesis and DNA damage.PLoS genetics · 2024Article
- Inflammatory signaling pathways in the treatment of Alzheimer's disease with inhibitors, natural products and metabolites (Review).International journal of molecular medicine · 2023Review
- Proline hydroxylation of CREB-regulated transcriptional coactivator 2 controls hepatic glucose metabolism.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Anti-inflammatory therapy of atherosclerosis: focusing on IKKβ.Journal of inflammation (London, England) · 2023Review
- Will We Unlock the Benefit of Metformin for Patients with Lung Cancer? Lessons from Current Evidence and New Hypotheses.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Modelling liver cancer microenvironment using a novel 3D culture system.Scientific reports · 2022Article
- Mitochondrial metabolic reprogramming by SIRT3 regulation ameliorates drug resistance in renal cell carcinoma.PloS one · 2022Article
- Isoform-specific Roles of Prolyl Hydroxylases in the Regulation of Pancreatic β-Cell Function.Endocrinology · 2022Article
- Coordinated pyruvate kinase activity is crucial for metabolic adaptation and cell survival during mitochondrial dysfunction.Human molecular genetics · 2021Article
- Prolyl-4-hydroxylase 3 maintains β cell glucose metabolism during fatty acid excess in mice.JCI insight · 2021Article
- Identification ofFrontiers in pharmacology · 2021Article
- Article
- Inhibition of prolyl hydroxylases increases hepatic insulin and decreases glucagon sensitivity by an HIF-2α-dependent mechanism.Molecular metabolism · 2020Article
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Authors and funding
16 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Glucagon-mediated gene transcription in the liver is critical for maintaining glucose homeostasis. Promoting the induction of gluconeogenic genes and blocking that of insulin receptor substrate (Irs)2 in hepatocytes contributes to the pathogenesis of type 2 diabetes. However, the molecular mechanism by which glucagon signalling regulates hepatocyte metabolism is not fully understood. We previously showed that a fasting-inducible signalling module consisting of general control non-repressed protein 5, co-regulator cAMP response element-binding protein binding protein/p300-interacting transactivator with Glu/Asp-rich carboxy-terminal domain 2, and protein kinase A is required for glucagon-induced transcription of gluconeogenic genes. The present study aimed to identify the downstream effectors of this module in hepatocytes by examining glucagon-induced potential target genes. One of these genes was prolyl hydroxylase domain (PHD)3, which suppressed stress signalling through inhibition of the IκB kinase-nuclear factor-κB pathway in a proline hydroxylase-independent manner to maintain insulin signalling. PHD3 was also required for peroxisome proliferator-activated receptor γ coactivator 1α-induced gluconeogenesis, which was dependent on proline hydroxylase activity, suggesting that PHD3 regulates metabolism in response to glucagon as well as insulin. These findings demonstrate that glucagon-inducible PHD3 regulates glucose metabolism by suppressing stress signalling and optimising gluconeogenesis and insulin signalling in hepatocytes.
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