ArticleNature medicine2009
Foxo1 integrates insulin signaling with mitochondrial function in the liver.
Article in Nature medicine, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 191 papers.
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Who cites it
191 citing papers in PubMed, 323 citations in OpenAlex.
- Female-specific reliance on endothelial FoxO1 governs vascular resilience and metabolic adaptation to obesity.Angiogenesis · 2026Article
- FOXO family and neurodegenerative diseases: Mechanisms of action and therapeutic potential.Redox biology · 2026Review
- Optical Redox Imaging of Breast Cancer NADH Redox Status Associated with PGC1α Gene Expression.Academic radiology · 2026Article
- CD73Nature communications · 2026Article
- Ovarian insulin signaling is intact despite systemic insulin resistance in a mouse model of polycystic ovary syndrome.Endocrinology · 2026Article
- Disruption of Hepatic Insulin Signaling Causes Phospholipid Dysregulation in Mice.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Studies of Foxo1 over the Past 25 Years: Mechanisms of Insulin Resistance and Glucose Dysregulation.Cells · 2026Review
- Therapeutic Potential of Flavonoids in Diabetes Mellitus Management: Molecular Insights and the Future Directions for Drug Design.Current drug discovery technologies · 2026Review
- Fructose and follistatin potentiate acute MASLD during complete hepatic insulin resistance.Nature communications · 2025Article
- Vorapaxar enhanced mitochondria-associated ferroptosis primes cancer immunotherapy via targeting FOXO1/HMOX1 axis.Cell reports. Medicine · 2025Article
- Endocannabinoid signaling is a critical link between circadian desynchronization and metabolic dysfunction.bioRxiv : the preprint server for biology · 2025Article
- Mitochondrial quality control in diabetes mellitus and complications: molecular mechanisms and therapeutic strategies.Cell death & disease · 2025Review
- Mitigation of chemotherapy-induced gut dysbiosis and diarrhea by supplementation with heat-killed Bacteroides fragilis.BMC medicine · 2025Article
- Connecting the Dots: Mitochondrial Dysfunction, PCOS, and Insulin Resistance-Insights and Therapeutic Advances.International journal of molecular sciences · 2025Review
- lncRNA TUG1 and kidney diseases.BMC nephrology · 2025Review
- Differential association of selenium exposure with insulin resistance and β-cell function in middle age and older adults.Nutrition & diabetes · 2025Article
- Human liver progenitor-like cells-derived extracellular vesicles promote liver regeneration during acute liver failure.Cell biology and toxicology · 2024Article
- The role of adipose tissue dysfunction in hepatic insulin resistance and T2D.The Journal of endocrinology · 2024Review
- The Foxo1-YAP-Notch1 axis reprograms STING-mediated innate immunity in NASH progression.Experimental & molecular medicine · 2024Article
- Mitochondrial fusion and altered beta-oxidation drive muscle wasting in a Drosophila cachexia model.EMBO reports · 2024Article
131 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
Type 2 diabetes is a complex disease that is marked by the dysfunction of glucose and lipid metabolism. Hepatic insulin resistance is especially pathogenic in type 2 diabetes, as it dysregulates fasting and postprandial glucose tolerance and promotes systemic dyslipidemia and nonalcoholic fatty liver disease. Mitochondrial dysfunction is closely associated with insulin resistance and might contribute to the progression of diabetes. Here we used previously generated mice with hepatic insulin resistance owing to the deletion of the genes encoding insulin receptor substrate-1 (Irs-1) and Irs-2 (referred to here as double-knockout (DKO) mice) to establish the molecular link between dysregulated insulin action and mitochondrial function. The expression of several forkhead box O1 (Foxo1) target genes increased in the DKO liver, including heme oxygenase-1 (Hmox1), which disrupts complex III and IV of the respiratory chain and lowers the NAD(+)/NADH ratio and ATP production. Although peroxisome proliferator-activated receptor-gamma coactivator-1alpha (Ppargc-1alpha) was also upregulated in DKO liver, it was acetylated and failed to promote compensatory mitochondrial biogenesis or function. Deletion of hepatic Foxo1 in DKO liver normalized the expression of Hmox1 and the NAD(+)/NADH ratio, reduced Ppargc-1alpha acetylation and restored mitochondrial oxidative metabolism and biogenesis. Thus, Foxo1 integrates insulin signaling with mitochondrial function, and inhibition of Foxo1 can improve hepatic metabolism during insulin resistance and the metabolic syndrome.
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