ArticleDiabetes2011
FoxO6 integrates insulin signaling with gluconeogenesis in the liver.
Article in Diabetes, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers.
What it found
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Who cites it
76 citing papers in PubMed, 134 citations in OpenAlex.
- Expression of FOXO6 is Associated With Oxidative Stress Level and Predicts the Prognosis in Hepatocellular Cancer: A Comparative Study.Medicine · 2016Trial
- Study on the expression changes of hepatic Gluconeogenesis-related proteins induced by insulin Overdose-related liver injury.Forensic toxicology · 2026Article
- Comparative Transcriptome Analysis of the Abdominal Ganglion Reveals Molecular Networks and Key Genes Underlying Thermal Tolerance in Red Swamp Crayfish (Animals : an open access journal from MDPI · 2026Article
- FOXO transcription factors in Alzheimer's Disease: balancing neuroprotection and neuronal degeneration.Molecular biology reports · 2026Review
- Admixture-driven structural variation diversity and its functional implications.National science review · 2026Article
- Functional properties of skeletal myotube-derived extracellular vesicles based on microRNA profiles: a comparative analysis with mesenchymal stem cell-derived extracellular vesicles.Scientific reports · 2026Article
- FOXO: a key target in regulating aging and age-related diseases.Biogerontology · 2026Review
- Multi-Ancestry Transcriptome-Wide Association Studies of Cognitive Function, White Matter Hyperintensity, and Alzheimer's Disease.International journal of molecular sciences · 2025Article
- Characteristics of different lipid droplet-mitochondrial contacts patterns during lipid droplet metabolism in T2DM-induced MASLD.Scientific reports · 2025Article
- Targeting the FoxJ3/FoxO6 axis suppresses hepatocellular carcinoma growth by inducing cell cycle arrest and apoptosis.American journal of translational research · 2025Article
- Modelling quiescence exit of neural stem cells reveals a FOXG1-FOXO6 axis.Disease models & mechanisms · 2024Article
- Endoplasmic reticulum stress induces hepatic steatosis through interaction between PPARα and FoxO6 in vivo and in vitro.Journal of molecular medicine (Berlin, Germany) · 2024Article
- Forkhead box O proteins: steering the course of stem cell fate.Cell regeneration (London, England) · 2024Review
- Article
- FoxO6-Mediated TXNIP Induces Lipid Accumulation in the Liver through NLRP3 Inflammasome Activation.Endocrinology and metabolism (Seoul, Korea) · 2024Article
- Forkhead box O1 transcription factor; a therapeutic target for diabetic cardiomyopathy.Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques · 2024Review
- Therapeutic Consequences of Targeting the IGF-1/PI3K/AKT/FOXO3 Axis in Sarcopenia: A Narrative Review.Cells · 2023Review
- FOXO family isoforms.Cell death & disease · 2023Review
- Article
- The Pathogenesis of Diabetes.International journal of molecular sciences · 2023Review
16 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
12 authors at 3 institutions in 1 country.
Funding
Abstract
objectiveExcessive endogenous glucose production contributes to fasting hyperglycemia in diabetes. This effect stems from inept insulin suppression of hepatic gluconeogenesis. To understand the underlying mechanisms, we studied the ability of forkhead box O6 (FoxO6) to mediate insulin action on hepatic gluconeogenesis and its contribution to glucose metabolism. RESEARCH DESIGN AND
methodsWe characterized FoxO6 in glucose metabolism in cultured hepatocytes and in rodent models of dietary obesity, insulin resistance, or insulin-deficient diabetes. We determined the effect of FoxO6 on hepatic gluconeogenesis in genetically modified mice with FoxO6 gain- versus loss-of-function and in diabetic db/db mice with selective FoxO6 ablation in the liver.
resultsFoxO6 integrates insulin signaling to hepatic gluconeogenesis. In mice, elevated FoxO6 activity in the liver augments gluconeogenesis, raising fasting blood glucose levels, and hepatic FoxO6 depletion suppresses gluconeogenesis, resulting in fasting hypoglycemia. FoxO6 stimulates gluconeogenesis, which is counteracted by insulin. Insulin inhibits FoxO6 activity via a distinct mechanism by inducing its phosphorylation and disabling its transcriptional activity, without altering its subcellular distribution in hepatocytes. FoxO6 becomes deregulated in the insulin-resistant liver, accounting for its unbridled activity in promoting gluconeogenesis and correlating with the pathogenesis of fasting hyperglycemia in diabetes. These metabolic abnormalities, along with fasting hyperglycemia, are reversible by selective inhibition of hepatic FoxO6 activity in diabetic mice.
conclusionsOur data uncover a FoxO6-dependent pathway by which the liver orchestrates insulin regulation of gluconeogenesis, providing the proof-of-concept that selective FoxO6 inhibition is beneficial for curbing excessive hepatic glucose production and improving glycemic control in diabetes.
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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.