ArticleThe Journal of nutrition2018
Intestinal DMT1 Is Essential for Optimal Assimilation of Dietary Copper in Male and Female Mice with Iron-Deficiency Anemia.
Article in The Journal of nutrition, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 1 of them a synthesis that pooled it.
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Who cites it
24 citing papers in PubMed, 1 synthesis or guideline pooled it, 30 citations in OpenAlex.
- Blood lead concentrations in children with iron deficiency anemia: a systematic review and meta-analysis.Environmental science and pollution research international · 2022Pooled it
- Balancing cellular copper levels via the post-translational regulation of copper transport.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2026Review
- Overlaps in mammalian iron and manganese homeostasis: recent advances.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2026Review
- Metallic Contaminants and Osteoporosis: a Review of the Gut-Bone Axis.Biological trace element research · 2026Review
- High intestinal iron absorption induced by decreased hepcidin leads to imbalance of iron metabolism in aging mice.Biogerontology · 2025Article
- Copper-instigated modulatory cell mortality mechanisms and progress in kidney diseases.Renal failure · 2025Review
- Mammalian copper homeostasis: physiological roles and molecular mechanisms.Physiological reviews · 2025Review
- Copper-Induced Cell Death in Renal Diseases: Molecular Mechanisms and Therapeutic Implications.Drug design, development and therapy · 2025Review
- Gut to brain: essential micronutrient and trace element manganese transport, function and toxicity.Frontiers in physiology · 2025Review
- In vivo silencing of intestinal DMT1 mitigates iron loading in β-thalassemia intermedia (Hbbth3/+) mice.Blood advances · 2024Article
- Metal ions overloading and cell death.Cell biology and toxicology · 2024Review
- The Molecular Mechanisms of Cuproptosis and Small-Molecule Drug Design in Diabetes Mellitus.Molecules (Basel, Switzerland) · 2024Review
- Oral iron therapy: Current concepts and future prospects for improving efficacy and outcomes.British journal of haematology · 2024Review
- Variations in Blood Copper and Possible Mechanisms During Pregnancy.Biological trace element research · 2024Review
- Short-term effects of roxadustat on serum copper and iron changes in a peritoneal dialysis patient.CEN case reports · 2023Article
- Comparison of apical and basolateral Cu treatment for iron-related gene regulation during deferoxamine induced iron deficiency.Genes & nutrition · 2022Article
- Four AAs increase DMT1 abundance in duodenal brush-border membrane vesicles and enhance iron absorption in iron-deprived mice.Blood advances · 2022Article
- Secretion and uptake of copper via a small copper carrier in blood fluid.Metallomics : integrated biometal science · 2022Article
- Chelators for Treatment of Iron and Copper Overload: Shift from Low-Molecular-Weight Compounds to Polymers.Polymers · 2021Review
- Iron, Copper, and Zinc Homeostasis: Physiology, Physiopathology, and Nanomediated Applications.Nanomaterials (Basel, Switzerland) · 2021Review
Corrections and comments
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Authors and funding
9 authors at 1 institution in 2 countries.
Funding
Abstract
Background: Divalent metal-ion transporter 1 (DMT1) may transport copper, but studies to date on this topic have been equivocal. Previously, an ex vivo experiment showed that intestinal copper transport was impaired in Dmt1-mutant Belgrade rats. Objective: In this study, we tested the hypothesis that intestinal DMT1 transports copper in vivo. Methods: Intestine-specific Dmt1 knockout (Dmt1int/int) mice and normal (control) littermates (Dmt1fl/fl) were used. In study 1, intestinal copper absorption was assessed in 7-wk-old mice of both sexes and genotypes by oral-intragastric gavage of 64Cu under normal and iron-deficiency anemia (IDA) conditions. In study 2, both sexes and genotypes of 8-wk-old mice were fed diets with adequate iron concentrations [72 parts per million (ppm)] plus adequate (9 ppm) or excessive (183 ppm) copper concentrations for 4 wk. Iron- and copper-related physiologic variables were subsequently assessed. Results: Study 1 showed that intestinal copper transport was enhanced in normal (∼11% increase in males, 35% in females) and anemic (∼42% increase in males, 35% in females) Dmt1int/int mice. Study 2 showed that, with adequate copper intakes, serum ceruloplasmin (Cp) activity was decreased (by ∼29% in males and 20% in females) and spleens were enlarged (by 3-fold in both sexes) in Dmt1int/int mice. Higher dietary copper increased hepatic copper concentrations (by ∼3.3-fold in males and 1.5-fold in females), restored serum Cp activity, and mitigated the noted splenomegaly in Dmt1int/int mice. Conclusions: Copper homeostasis was disrupted in Dmt1int/int mice, particularly during IDA, despite the noted increases in intestinal copper transport. This was exemplified by the fact that extra dietary copper was required to restore serum Cp activity (a biomarker of copper status) and reduce the severity of the noted splenomegaly (which could reflect changes in erythropoietic demand) in Dmt1int/int mice. Collectively, these observations show that intestinal DMT1 is essential for the assimilation of sufficient quantities of dietary copper to maintain systemic copper homeostasis during IDA.
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