ArticleThe Journal of biological chemistry2009
FoxO1 and HNF-4 are involved in regulation of hepatic glucokinase gene expression by resveratrol.
Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers, 1 of them a synthesis that pooled it.
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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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
35 citing papers in PubMed, 1 synthesis or guideline pooled it, 76 citations in OpenAlex.
- Evidence of traditional Chinese medicine for treating type 2 diabetes mellitus: from molecular mechanisms to clinical efficacy.Pharmaceutical biology · 2024Pooled it
- Resveratrol supplementation improves lipid and glucose metabolism in high-fat diet-fed blunt snout bream.Fish physiology and biochemistry · 2018Trial
- Insect Lipids: Structure, Classification and Function.Advances in experimental medicine and biology · 2026Review
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- Serum Transferrin Predicts New-Onset Type 2 Diabetes in Koreans: A 4-Year Retrospective Longitudinal Study.Endocrinology and metabolism (Seoul, Korea) · 2020Article
- Resveratrol long-term treatment differentiates INS-1E beta-cell towards improved glucose response and insulin secretion.Pflugers Archiv : European journal of physiology · 2019Article
- Hallmarks of Aging in the Liver.Computational and structural biotechnology journal · 2019Review
- Natural products, an important resource for discovery of multitarget drugs and functional food for regulation of hepatic glucose metabolism.Drug design, development and therapy · 2018Review
- Selective Inhibition of FOXO1 Activator/Repressor Balance Modulates Hepatic Glucose Handling.Cell · 2017Article
- FOXO transcription factors protect against the diet-induced fatty liver disease.Scientific reports · 2017Article
- Integrated Regulation of Hepatic Lipid and Glucose Metabolism by Adipose Triacylglycerol Lipase and FoxO Proteins.Cell reports · 2016Article
- Article
- Role of transcription factor acetylation in the regulation of metabolic homeostasis.Protein & cell · 2015Review
- Transcriptional Factors Mediating Retinoic Acid Signals in the Control of Energy Metabolism.International journal of molecular sciences · 2015Review
- A mutant allele encoding DNA binding-deficient FoxO1 differentially regulates hepatic glucose and lipid metabolism.Diabetes · 2015Article
- Linking diet to acne metabolomics, inflammation, and comedogenesis: an update.Clinical, cosmetic and investigational dermatology · 2015Review
- Hepatic glucose sensing and integrative pathways in the liver.Cellular and molecular life sciences : CMLS · 2014Review
- GSK3β-dependent phosphorylation alters DNA binding, transactivity and half-life of the transcription factor USF2.PloS one · 2014Article
- Article
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 3 countries.
Funding
Abstract
Resveratrol, a polyphenol derived from grapes, exerts important effects on glucose and lipid metabolism, yet detailed mechanisms mediating these effects remain unknown. The liver plays a central role in energy homeostasis, and glucokinase (GK) is a key enzyme involved in glucose utilization. Resveratrol activates SIRT1 (sirtuin 1), which promotes deacetylation of the forkhead transcription factor FoxO1. Previously, we reported that FoxO1 can suppress and that HNF-4 can stimulate GK expression in the liver. Here, we examined the role of FoxO1 and HNF-4 in mediating resveratrol effects on liver GK expression. Resveratrol suppressed hepatic GK expression in vivo and in isolated hepatocytes, and knocking down FoxO1 with shRNAs disrupted this effect. Reporter gene, gel shift, supershift assay, and chromatin immunoprecipitation studies show that FoxO1 binds to the GK promoter and that the interplay between FoxO1 and HNF-4 within the GK promoter is essential for mediating the effects of resveratrol. Resveratrol promotes deacetylation of FoxO1 and enhances its recruitment to the FoxO-binding element. Conversely, resveratrol suppresses recruitment of HNF-4 to its binding site, and knockdown of FoxO1 blocks this effect of resveratrol. Coprecipitation and chromatin immunoprecipitation studies show that resveratrol enhances interaction between FoxO1 and HNF-4, reduces binding of HNF-4 to its own site, and promotes its recruitment to the FoxO site in a FoxO1-dependent manner. These results provide the first evidence that resveratrol represses GK expression via FoxO1 and that the interaction between FoxO1 and HNF-4 contributes to these effects of resveratrol.
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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.