ArticlePloS one2013
Deletion of hepatic FoxO1/3/4 genes in mice significantly impacts on glucose metabolism through downregulation of gluconeogenesis and upregulation of glycolysis.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
66 citing papers in PubMed, 110 citations in OpenAlex.
- FoxO transcription factors coordinate the urea cycle and gluconeogenesis by controllingiScience · 2026Article
- Hepatic Glucocorticoid Receptor Action and Glucose Homeostasis.Endocrine reviews · 2026Review
- FOXO: a key target in regulating aging and age-related diseases.Biogerontology · 2026Review
- Autophagy in the liver.Autophagy reports · 2026Review
- Inter-Organ Crosstalk and Regulatory Mechanisms of Skeletal Muscle-Derived Extracellular Vesicles in Systemic Metabolic Homeostasis.Journal of cellular and molecular medicine · 2025Review
- Decoding androgen excess in polycystic ovary syndrome: Roles of insulin resistance and other key intraovarian and systemic factors.World journal of diabetes · 2025Review
- Transcriptome and Metabolome Analyses Reveal High-Altitude Adaptation in the Qinghai Toad-Headed LizardBiology · 2025Article
- Coordinated Regulation of Renal Glucose Reabsorption and Gluconeogenesis by mTORC2 and Potassium.Journal of the American Society of Nephrology : JASN · 2025Article
- Identification and Functional Analysis of Key microRNAs in the Early Extrauterine Environmental Adaptation of Piglets.International journal of molecular sciences · 2025Article
- Insulin resistance and its association with coronary heart disease: insights from bioinformatics analysis.Frontiers in endocrinology · 2025Article
- PI3KR1 and AKT1 in largemouth bass (Micropterus salmoides): molecular cloning, characterization, and its involvement in the alleviation of hepatic glycogen deposition caused by insulin inclusion in vitro.Fish physiology and biochemistry · 2024Article
- The Molecular Mechanism of Farnesoid X Receptor Alleviating Glucose Intolerance in Turbot (Cells · 2024Article
- Emerging role of sirtuins in non‑small cell lung cancer (Review).Oncology reports · 2024Review
- Cryptocaryone induces apoptosis in human hepatocellular carcinoma cells by inhibiting aerobic glycolysis through Akt and c-Src signaling pathways.Journal of food and drug analysis · 2023Article
- GB1a Activates SIRT6 to Regulate Lipid Metabolism in Mouse Primary Hepatocytes.International journal of molecular sciences · 2023Article
- FoxO1 as a tissue-specific therapeutic target for type 2 diabetes.Frontiers in endocrinology · 2023Review
- Hepatic FoxOs link insulin signaling with plasma lipoprotein metabolism through an apolipoprotein M/sphingosine-1-phosphate pathway.The Journal of clinical investigation · 2022Article
- A Study of the Protective Effect of Bushen Huoxue Prescription on Cerebral Microvascular Endothelia Based on Proteomics and Bioinformatics.Evidence-based complementary and alternative medicine : eCAM · 2022Article
- Long noncoding RNA matrilineal expression gene 3 inhibits hepatocellular carcinoma progression by targeting microRNA-5195-3p and regulating the expression of forkhead box O1.Bioengineered · 2021Article
- Role of FoxO transcription factors in aging and age-related metabolic and neurodegenerative diseases.Cell & bioscience · 2021Review
6 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Forkhead transcription factors FoxO1/3/4 have pleiotrophic functions including anti-oxidative stress and metabolism. With regard to glucose metabolism, most studies have been focused on FoxO1. To further investigate their hepatic functions, we generated liver-specific FoxO1/3/4 knockout mice (LTKO) and examined their collective impacts on glucose homeostasis under physiological and pathological conditions. As compared to wild-type mice, LTKO mice had lower blood glucose levels under both fasting and non-fasting conditions and they manifested better glucose and pyruvate tolerance on regular chow diet. After challenged by a high-fat diet, wild-type mice developed type 2 diabetes, but LTKO mice remained euglycemic and insulin-sensitive. To understand the underlying mechanisms, we examined the roles of SIRT6 (Sirtuin 6) and Gck (glucokinase) in the FoxO-mediated glucose metabolism. Interestingly, ectopic expression of SIRT6 in the liver only reduced gluconeogenesis in wild-type but not LTKO mice whereas knockdown of Gck caused glucose intolerance in both wild-type and LTKO mice. The data suggest that both decreased gluconeogenesis and increased glycolysis may contribute to the overall glucose phenotype in the LTKO mice. Collectively, FoxO1/3/4 transcription factors play important roles in hepatic glucose homeostasis.
Indexed as
Identifiers
What OpenQuestion holds
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.