ArticleThe Journal of biological chemistry2016
Hepatic ZIP14-mediated Zinc Transport Contributes to Endosomal Insulin Receptor Trafficking and Glucose Metabolism.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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.
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.
Who cites it
39 citing papers in PubMed, 59 citations in OpenAlex.
- Zinc accumulation in macrophages exacerbates metabolic dysfunction-associated steatotic liver disease progression.Signal transduction and targeted therapy · 2026Article
- Zinc as a master regulator of intracellular organelle homeostasis.Experimental & molecular medicine · 2026Review
- A full-length single nuclei transcriptomic atlas of human skeletal muscle insulin resistance.bioRxiv : the preprint server for biology · 2026Article
- Zinc, type 2 diabetes, diabetic kidney disease: focus on hypoxia.Frontiers in endocrinology · 2026Review
- Association of serum zinc concentration with multiple surrogates of insulin resistance in a population-based study.Scientific reports · 2025Article
- Regulation of iron metabolism in ferroptosis: From mechanism research to clinical translation.Journal of pharmaceutical analysis · 2025Review
- Zrt-Irt-like Proteins (ZIP) Family Zinc Transporters: Emerging Players in Pancreatic β Cell Function and Insulin Regulation.The Journal of nutrition · 2025Review
- The Role of Solute Carrier Family Transporters in Hepatic Steatosis and Hepatic Fibrosis.Journal of clinical and translational hepatology · 2025Review
- Roles of zinc and zinc transporters in development, progression, and treatment of inflammatory bowel disease (IBD).Frontiers in nutrition · 2025Review
- Pretreatment with aqueousHeliyon · 2024Article
- Hyperactive behaviour of growth differentiation factor- 15 (GDF-15) in conjunction with iron trafficking transporters and suppression of Nrf-2 gene in diabetes and metabolic syndrome.Molecular and cellular biochemistry · 2024Article
- Marginal Maternal Zinc Deficiency Produces Liver Damage and Altered Zinc Transporter Expression in Offspring Male Rats.Biological trace element research · 2024Article
- The impact of solute carrier proteins on disrupting substance regulation in metabolic disorders: insights and clinical applications.Frontiers in pharmacology · 2024Review
- Absence ofAmerican journal of physiology. Endocrinology and metabolism · 2024Article
- Unlocking the brain's zinc code: implications for cognitive function and disease.Frontiers in biophysics · 2024Article
- Metal transporter SLC39A14/ZIP14 modulates regulation between the gut microbiome and host metabolism.American journal of physiology. Gastrointestinal and liver physiology · 2023Article
- Review
- Anemia, Iron Deficiency, and Iron Regulators in Pancreatic Ductal Adenocarcinoma Patients: A Comprehensive Analysis.Current oncology (Toronto, Ont.) · 2023Article
- Modulation of Zinc Transporter Expressions by Additional Zinc in C2C12 Cells Cultured in a High Glucose Environment and in the Presence of Insulin or Interleukin-6.Biological trace element research · 2023Article
- Sucrose-induced hyperglycemia dysregulates intestinal zinc metabolism and integrity: risk factors for chronic diseases.Frontiers in nutrition · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 1 institution in 2 countries.
Funding
Abstract
Zinc influences signaling pathways through controlled targeted zinc transport. Zinc transporter Zip14 KO mice display a phenotype that includes impaired intestinal barrier function with low grade chronic inflammation, hyperinsulinemia, and increased body fat, which are signatures of diet-induced diabetes (type 2 diabetes) and obesity in humans. Hyperglycemia in type 2 diabetes and obesity is caused by insulin resistance. Insulin resistance results in inhibition of glucose uptake by liver and other peripheral tissues, principally adipose and muscle and with concurrently higher hepatic glucose production. Therefore, modulation of hepatic glucose metabolism is an important target for antidiabetic treatment approaches. We demonstrate that during glucose uptake, cell surface abundance of zinc transporter ZIP14 and mediated zinc transport increases. Zinc is distributed to multiple sites in hepatocytes through sequential translocation of ZIP14 from plasma membrane to early and late endosomes. Endosomes from Zip14 KO mice were zinc-deficient because activities of the zinc-dependent insulin-degrading proteases insulin-degrading enzyme and cathepsin D were impaired; hence insulin receptor activity increased. Transient increases in cytosolic zinc levels are concurrent with glucose uptake and suppression of glycogen synthesis. In contrast, Zip14 KO mice exhibited greater hepatic glycogen synthesis and impaired gluconeogenesis and glycolysis related to low cytosolic zinc levels. We can conclude that ZIP14-mediated zinc transport contributes to regulation of endosomal insulin receptor activity and glucose homeostasis in hepatocytes. Therefore, modulation of ZIP14 transport activity presents a new target for management of diabetes and other glucose-related disorders.
Indexed as
Identifiers
What OpenQuestion holds
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.