ArticlePloS one2013
The zinc transporter Zip5 (Slc39a5) regulates intestinal zinc excretion and protects the pancreas against zinc toxicity.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 72 citations in OpenAlex.
- The SLC-ome of membrane transport: from molecular discovery to physiology and clinical applications.Physiological reviews · 2026Review
- Zinc as a master regulator of intracellular organelle homeostasis.Experimental & molecular medicine · 2026Review
- Intestinal Effects of Brewers' Spent Grain Extract In Ovo (Animals : an open access journal from MDPI · 2025Article
- SLC30 (ZnT) and SLC39 (ZIP) zinc transporter families: from gatekeepers of zinc homeostasis to promoters of tumorigenesis and targets for clinical therapy.Frontiers in immunology · 2025Review
- Zinc and its binding proteins: essential roles and therapeutic potential.Archives of toxicology · 2025Review
- Article
- Role of zinc in health and disease.Clinical and experimental medicine · 2024Review
- Zinc proteinate with moderate chelation strength enhances zinc absorption by upregulating the expression of zinc and amino acid transporters in primary cultured duodenal epithelial cells of broiler embryos.Journal of animal science · 2024Article
- The organic zinc with moderate chelation strength enhances the expression of related transporters in the jejunum and ileum of broilers.Poultry science · 2023Article
- Analysis of the Association of Two SNPs in the Promoter Regions of theAnimals : an open access journal from MDPI · 2022Article
- Article
- Review
- Sophisticated expression responses of ZNT1 and MT in response to changes in the expression of ZIPs.Scientific reports · 2022Article
- Zinc: Roles in pancreatic physiology and disease.Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.] · 2020Review
- Maintenance of Intestinal Epithelial Homeostasis by Zinc Transporters.Digestive diseases and sciences · 2019Review
- Identification of a Radiosensitivity Molecular Signature Induced by Enzalutamide in Hormone-sensitive and Hormone-resistant Prostate Cancer Cells.Scientific reports · 2019Article
- The zinc transporter Slc39a5 controls glucose sensing and insulin secretion in pancreatic β-cells via Sirt1- and Pgc-1α-mediated regulation of Glut2.Protein & cell · 2019Article
- Contribution of Zinc and Zinc Transporters in the Pathogenesis of Inflammatory Bowel Diseases.Journal of immunology research · 2019Review
- Altered zinc balance in the Atp7bMetallomics : integrated biometal science · 2018Article
- Differential expression of zinc transporters accompanies the differentiation of C2C12 myoblasts.Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS) · 2018Article
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3 authors at 1 institution in 1 country.
Funding
Abstract
backgroundZIP5 localizes to the baso-lateral membranes of intestinal enterocytes and pancreatic acinar cells and is internalized and degraded coordinately in these cell-types during periods of dietary zinc deficiency. These cell-types are thought to control zinc excretion from the body. The baso-lateral localization and zinc-regulation of ZIP5 in these cells are unique among the 14 members of the Slc39a family and suggest that ZIP5 plays a role in zinc excretion. METHODS/PRINCIPAL
findingsWe created mice with floxed Zip5 genes and deleted this gene in the entire mouse or specifically in enterocytes or acinar cells and then examined the effects on zinc homeostasis. We found that ZIP5 is not essential for growth and viability but total knockout of ZIP5 led to increased zinc in the liver in mice fed a zinc-adequate (ZnA) diet but impaired accumulation of pancreatic zinc in mice fed a zinc-excess (ZnE) diet. Loss-of-function of enterocyte ZIP5, in contrast, led to increased pancreatic zinc in mice fed a ZnA diet and increased abundance of intestinal Zip4 mRNA. Finally, loss-of-function of acinar cell ZIP5 modestly reduced pancreatic zinc in mice fed a ZnA diet but did not impair zinc uptake as measured by the rapid accumulation of (67)zinc. Retention of pancreatic (67)zinc was impaired in these mice but the absence of pancreatic ZIP5 sensitized them to zinc-induced pancreatitis and exacerbated the formation of large cytoplasmic vacuoles containing secretory protein in acinar cells.
conclusionsThese studies demonstrate that ZIP5 participates in the control of zinc excretion in mice. Specifically, they reveal a paramount function of intestinal ZIP5 in zinc excretion but suggest a role for pancreatic ZIP5 in zinc accumulation/retention in acinar cells. ZIP5 functions in acinar cells to protect against zinc-induced acute pancreatitis and attenuate the process of zymophagy. This suggests that it may play a role in autophagy.
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