ArticleDiabetes2021
Heme Oxygenase-1 Regulates Ferrous Iron and Foxo1 in Control of Hepatic Gluconeogenesis.
Article in Diabetes, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 27 citations in OpenAlex.
- Moderate iron restriction improves metabolism via epigenetic regulation of GDF15.The Journal of nutritional biochemistry · 2026Article
- Hepatic Gluconeogenesis and the Antidepressant Effects of Exercise: A Narrative Review.Metabolites · 2026Review
- Febuxostat Improves MASLD in Male Rats: Roles of XOR Inhibition and Associated JNK/NRF2/HO-1 Pathway Changes.International journal of molecular sciences · 2026Article
- Studies of Foxo1 over the Past 25 Years: Mechanisms of Insulin Resistance and Glucose Dysregulation.Cells · 2026Review
- FOXO1 phosphorylation as a context-dependent molecular switch in cancer: from mechanisms to precision therapy.World journal of surgical oncology · 2025Review
- CHIP mediates glucagon action on hepatic glucose production via regulating Smad3 ubiquitination.Diabetes, obesity & metabolism · 2025Article
- Heme oxygenase, biliverdin reductase, and bilirubin pathways regulate oxidative stress and insulin resistance: a focus on diabetes and therapeutics.Clinical science (London, England : 1979) · 2025Review
- Autophagy inhibitor-sensitized artificially activated neutrophils against hepatocellular carcinoma.Theranostics · 2025Article
- Article
- [Research progress on the mechanism of action of heme oxygenase-1 regulating ferroptosis in non-alcoholic fatty liver disease].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2024Review
- Regulation of Macronutrients in Insulin Resistance and Glucose Homeostasis during Type 2 Diabetes Mellitus.Nutrients · 2023Review
- Transcription Factor Forkhead Box O1 Mediates Transforming Growth Factor-β1-Induced Apoptosis in Hepatocytes.The American journal of pathology · 2023Article
- Reciprocal Regulation of Hepatic TGF-β1 and Foxo1 Controls Gluconeogenesis and Energy Expenditure.Diabetes · 2023Article
- KSHV hijacks FoxO1 to promote cell proliferation and cellular transformation by antagonizing oxidative stress.Journal of medical virology · 2023Article
- Iron and the Pathophysiology of Diabetes.Annual review of physiology · 2023Review
- Prenylated indole-terpenoids with antidiabetic activities fromFrontiers in microbiology · 2023Article
- Pea protein hydrolysate reduces blood glucose in high-fat diet and streptozotocin-induced diabetic mice.Frontiers in nutrition · 2023Article
- Enhanced sciatic nerve regeneration by relieving iron-overloading and organelle stress with the nanofibrous P(MMD-co-LA)/DFO conduits.Materials today. Bio · 2022Article
- FoxO transcription factors in mitochondrial homeostasis.The Biochemical journal · 2022Article
- Activation of Nrf2 signaling: A key molecular mechanism of protection against cardiovascular diseases by natural products.Frontiers in pharmacology · 2022Review
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
The liver is a key player for maintaining glucose homeostasis. Excessive hepatic glucose production is considered to be a key for the onset of type 2 diabetes. The primary function of heme oxygenase-1 (HO1) is to catalyze the degradation of heme into biliverdin, ferrous iron, and carbon monoxide. Previous studies have demonstrated that the degradation of heme by HO1 in the liver results in mitochondrial dysfunction and drives insulin resistance. In this study, by overexpressing HO1 in hepatocytes and mice, we showed that HO1 promotes gluconeogenesis in a Foxo1-dependent manner. Importantly, HO1 overexpression increased the generation of ferrous iron in the liver, which further activates nuclear factor-κB and phosphorylates Foxo1 at Ser273 to enhance gluconeogenesis. We further assessed the role of HO1 in insulin-resistant liver-specific knockout of IRS1 and IRS2 genes (L-DKO) mice, which exhibit upregulation of HO1 in the liver and hepatic ferrous iron overload. HO1 knockdown by shRNA or treatment of iron chelator rescued the aberrant gluconeogenesis in L-DKO mice. In addition, we found that systemic iron overload promotes gluconeogenesis by activating the hepatic protein kinase A→Foxo1 axis. Thus, our results demonstrate the role of HO1 in regulating hepatic iron status and Foxo1 to control gluconeogenesis and blood glucose.
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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.