ArticleJournal of molecular medicine (Berlin, Germany)2017
Uncoupled iron homeostasis in type 2 diabetes mellitus.
Article in Journal of molecular medicine (Berlin, Germany), 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers, 1 of them a synthesis that pooled it.
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Who cites it
39 citing papers in PubMed, 1 synthesis or guideline pooled it, 62 citations in OpenAlex.
- Ferroptosis and ferritinophagy in diabetes complications.Molecular metabolism · 2022Pooled it
- Crosstalk between autophagy and ferroptosis in diabetes.Genes & diseases · 2026Review
- Deciphering the Iron Metabolism and Ferroptosis in Diabetic Wound Healing.Current diabetes reviews · 2026Review
- Association of serum zinc concentration with multiple surrogates of insulin resistance in a population-based study.Scientific reports · 2025Article
- Natural Products as Modulators of Iron Metabolism and Ferroptosis in Diabetes and Its Complications.Nutrients · 2025Review
- Inhibition of HMOX1 alleviates diabetic cardiomyopathy by targeting ferroptosis.Acta biochimica et biophysica Sinica · 2025Article
- The link between ferroptosis and autophagy in myocardial ischemia/reperfusion injury: new directions for therapy.Journal of cardiovascular translational research · 2025Review
- Iron overload is closely associated with metabolic dysfunction-associated fatty liver disease in type 2 diabetes.Obesity (Silver Spring, Md.) · 2025Article
- Causal Associations of Iron Status With the Renal Function and Diabetic Nephropathy in Patients With Diabetes Mellitus: A Two-Sample Mendelian Randomization Study.Journal of diabetes research · 2025Article
- Phospholipids and peroxisomes in ferroptosis: the therapeutic target of acupuncture regulating vascular cognitive impairment and dementia.Frontiers in aging neuroscience · 2025Review
- The role of metal ion metabolism in the pathogenesis of diabetes and associated complications.Frontiers in endocrinology · 2025Review
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- Mitophagy-related regulated cell death: molecular mechanisms and disease implications.Cell death & disease · 2024Review
- Ferritinophagy: A novel insight into the double-edged sword in ferritinophagy-ferroptosis axis and human diseases.Cell proliferation · 2024Review
- Association of Blast Exposure in Military Breaching with Intestinal Permeability Blood Biomarkers Associated with Leaky Gut.International journal of molecular sciences · 2024Article
- Iron Chelator Deferoxamine Alleviates Progression of Diabetic Nephropathy by Relieving Inflammation and Fibrosis in Rats.Biomolecules · 2023Article
- Excessive iron inhibits insulin secretion via perturbing transcriptional regulation of SYT7 by OGG1.Cellular and molecular life sciences : CMLS · 2023Article
- Consensus Statement on the definition and classification of metabolic hyperferritinaemia.Nature reviews. Endocrinology · 2023Review
- Defective NCOA4-dependent ferroptosis in senescent fibroblasts retards diabetic wound healing.Cell death discovery · 2023Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Diabetes mellitus is frequently associated with iron overload conditions, such as primary and secondary hemochromatosis. Conversely, patients affected by type 2 diabetes mellitus (T2DM) show elevated ferritin levels, a biomarker for increased body iron stores. Despite these documented associations between dysregulated iron metabolism and T2DM, the underlying mechanisms are poorly understood. Here, we show that T2DM patients have reduced serum levels of hepcidin, the iron-regulated hormone that maintains systemic iron homeostasis. Consistent with this finding, we also observed an increase in circulating iron and ferritin levels. Our analysis of db/db mice demonstrates that this model recapitulates the systemic alterations observed in patients. Interestingly, db/db mice show an overall hepatic iron deficiency despite unaltered expression of ferritin and the iron importer TfR1. In addition, the liver correctly senses increased circulating iron levels by activating the BMP/SMAD signaling pathway even though hepcidin expression is decreased. We show that increased AKT phosphorylation may override active BMP/SMAD signaling and decrease hepcidin expression in 10-week old db/db mice. We conclude that the metabolic alterations occurring in T2DM impact on the regulation of iron homeostasis on multiple levels. As a result, metabolic perturbations induce an "iron resistance" phenotype, whereby signals that translate increased circulating iron levels into hepcidin production, are dysregulated. KEY MESSAGES: T2DM patients show increased circulating iron levels. T2DM is associated with inappropriately low hepcidin levels. Metabolic alterations in T2DM induce an "iron resistance" phenotype.
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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.