Evidence map›Paper›PMID 30137476›Full record

ArticleThe Journal of nutrition2018

Intestinal DMT1 Is Essential for Optimal Assimilation of Dietary Copper in Male and Female Mice with Iron-Deficiency Anemia.

Xiaoyu Wang, Shireen Rl Flores, Jung-Heun Ha, Caglar Doguer, Regina R Woloshun, Ping Xiang, Astrid Grosche, Sadasivan Vidyasagar, James F Collins

Open access · bronzeAbstract read
In one paragraph

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.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed, 1 pooled it
1.5field-weighted citation impact, top 19% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

24 citing papers in PubMed, 1 synthesis or guideline pooled it, 30 citations in OpenAlex.

  1. Pooled it
  2. 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 · 2026
    Review
  3. Overlaps in mammalian iron and manganese homeostasis: recent advances.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2026
    Review
  4. Review
  5. Article
  6. Review
  7. Review
  8. Review
  9. Review
  10. Article
  11. Metal ions overloading and cell death.Cell biology and toxicology · 2024
    Review
  12. Review
  13. Review
  14. Review
  15. Article
  16. Article
  17. Article
  18. Secretion and uptake of copper via a small copper carrier in blood fluid.Metallomics : integrated biometal science · 2022
    Article
  19. Review
  20. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 1 institution in 2 countries.

Xiaoyu WangDepartments of Food Science and Human Nutrition, University of Florida, Gainesville, FL.
Shireen Rl FloresDepartments of Food Science and Human Nutrition, University of Florida, Gainesville, FL.
Jung-Heun HaDepartments of Food Science and Human Nutrition, University of Florida, Gainesville, FL.
Caglar DoguerDepartments of Food Science and Human Nutrition, University of Florida, Gainesville, FL.
Regina R WoloshunDepartments of Food Science and Human Nutrition, University of Florida, Gainesville, FL.
Ping XiangDepartments of Food Science and Human Nutrition, University of Florida, Gainesville, FL.
Astrid GroscheDepartments of Radiation Oncology, University of Florida, Gainesville, FL.
Sadasivan VidyasagarDepartments of Radiation Oncology, University of Florida, Gainesville, FL.
James F CollinsDepartments of Food Science and Human Nutrition, University of Florida, Gainesville, FL.
University of Florida · US

Funding

Molecular Mechanisms of Intestinal Metal Ion Transport During Iron-DeficiencyR01DK074867 · NIDDK · UNIVERSITY OF FLORIDA · PI COLLINS, JAMES F., VIDYASAGAR, SADASIVAN · 2007 to 2022
$5.1M
Divalent Metal-ion Transporter 1 as a Therapeutic Target to Optimize Intestinal Iron TransportR01DK109717 · NIDDK · UNIVERSITY OF FLORIDA · PI COLLINS, JAMES F. · 2016 to 2020
$2.6M
NIDDK NIH HHS R01 DK074867NIDDK NIH HHS R01 DK109717
6 · The paper itself

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.

Indexed as

Intestinal AbsorptionIron DeficienciesAnemia, Iron-DeficiencyAnimalsBiological AvailabilityCation Transport ProteinsCeruloplasminCopperDietFemaleHomeostasisIntestinesIonsIronLiverMaleCation Transport ProteinsCeruloplasminCopperIonsIronSolute Carrier Family 11, Member 2

Identifiers

PMID30137476
PMCPMC6074787
OpenAlexW2885972611

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

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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.