ArticleCell metabolism2022
TOX4, an insulin receptor-independent regulator of hepatic glucose production, is activated in diabetic liver.
Article in Cell metabolism, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 27 citations in OpenAlex.
- Intermediate leucine catabolism is associated with longevity and sustained reproduction in grasshoppers.GeroScience · 2026Article
- Epigenetic repression of hepatocyte FoxO1 disrupts local immune homeostasis and promotes liver inflammation.Hepatology (Baltimore, Md.) · 2026Article
- Absence of Thioredoxin Domain Containing 5 Improves Glucose Tolerance and Insulin Sensitivity in Male Mice.International journal of molecular sciences · 2026Article
- Dietary supplementation of Lemna minor improves glycemic regulation in grass carp (Ctenopharyngodon idella).Scientific reports · 2026Article
- Shared genetic architecture between anxiety, depression and erectile dysfunction: a genome-wide cross-trait analysis.Translational andrology and urology · 2025Article
- Genomic medicine in hepatology: mechanisms and liver treatment strategies.Molecular medicine (Cambridge, Mass.) · 2025Review
- Insulin resistance in type 2 diabetes mellitus.Nature reviews. Endocrinology · 2025Review
- TOX4 Inhibition in Chronic Hyperglycemia: Effects on Glycation Stress, Hepatic Protection, Epigenetic Mechanisms, Signaling Pathways, and Beta Cell Dynamics.Current drug metabolism · 2025Review
- The role of adipose tissue dysfunction in hepatic insulin resistance and T2D.The Journal of endocrinology · 2024Review
- Activation of the insulin receptor by insulin-like growth factor 2.Nature communications · 2024Article
- Myofiber-type-dependent 'boulder' or 'multitudinous pebble' formations across distinct amylopectinoses.Acta neuropathologica · 2024Article
- Maternal nutrient metabolism in the liver during pregnancy.Frontiers in endocrinology · 2024Review
- Mulberry leaf ameliorate STZ induced diabetic rat by regulating hepatic glycometabolism and fatty acid β-oxidation.Frontiers in pharmacology · 2024Article
- Hepatic retinaldehyde deficiency is involved in diabetes deterioration by enhancing PCK1- and G6PC-mediated gluconeogenesis.Acta pharmaceutica Sinica. B · 2023Article
- The E3 ubiquitin ligase NEDD4-1 protects against acetaminophen-induced liver injury by targeting VDAC1 for degradation.Acta pharmaceutica Sinica. B · 2023Article
- Hepatic Sam68 Regulates Systemic Glucose Homeostasis and Insulin Sensitivity.International journal of molecular sciences · 2022Article
- Estradiol (E2) Improves Glucose-Stimulated Insulin Secretion and Stabilizes GDM Progression in a Prediabetic Mouse Model.International journal of molecular sciences · 2022Article
- Parathyroid hormone alleviates non-alcoholic liver steatosisFrontiers in endocrinology · 2022Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
Increased hepatic glucose production (HGP) contributes to hyperglycemia in type 2 diabetes. Hormonal regulation of this process is primarily, but not exclusively, mediated by the AKT-FoxO1 pathway. Here, we show that cAMP and dexamethasone regulate the high-mobility group superfamily member TOX4 to mediate HGP, independent of the insulin receptor/FoxO1 pathway. TOX4 inhibition decreases glucose production in primary hepatocytes and liver and increases glucose tolerance. Combined genetic ablation of TOX4 and FoxO1 in liver has additive effects on glucose tolerance and gluconeogenesis. Moreover, TOX4 ablation fails to reverse the metabolic derangement brought by insulin receptor knockout. TOX4 expression is increased in livers of patients with steatosis and diabetes and in diet-induced obese and db/db mice. In the latter two murine models, knockdown Tox4 decreases glycemia and improves glucose tolerance. We conclude that TOX4 is an insulin receptor-independent regulator of HGP and a candidate contributor to the pathophysiology of diabetes.
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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.