ArticleThe Journal of biological chemistry2011
Glucose regulates free cytosolic Zn²⁺ concentration, Slc39 (ZiP), and metallothionein gene expression in primary pancreatic islet β-cells.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers, 1 of them a synthesis that pooled it.
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Who cites it
65 citing papers in PubMed, 1 synthesis or guideline pooled it, 115 citations in OpenAlex.
- Expression of the ZIP/SLC39A transporters in β-cells: a systematic review and integration of multiple datasets.BMC genomics · 2017Pooled it
- Article
- The SLC-ome of membrane transport: from molecular discovery to physiology and clinical applications.Physiological reviews · 2026Review
- Zinc Homeostasis and the Risk of Type 2 Diabetes: Complex Role of ZnT8 in Insulin and Glucagon Secretion.Current nutrition reports · 2026Review
- Zinc, type 2 diabetes, diabetic kidney disease: focus on hypoxia.Frontiers in endocrinology · 2026Review
- Persistent Inflammation, Maladaptive Remodeling, and Fibrosis in the Kidney Following Long COVID-like MHV-1 Mouse Model.Diseases (Basel, Switzerland) · 2025Article
- Zrt-Irt-like Proteins (ZIP) Family Zinc Transporters: Emerging Players in Pancreatic β Cell Function and Insulin Regulation.The Journal of nutrition · 2025Review
- Novel impact of metal ion-induced cell death on diabetic cardiomyopathy pathogenesis and therapy.Apoptosis : an international journal on programmed cell death · 2025Review
- ZIP7 contributes to the pathogenesis of diabetic cardiomyopathy by suppressing mitophagy in mouse hearts.Cardiovascular diabetology · 2024Article
- Pancreatic Antioxidative Defense and Heat Shock Proteins Prevent Islet of Langerhans Cell Death After Chronic Oral Exposure to Cadmium LOAEL Dose.Biological trace element research · 2024Article
- Intracellular zinc signaling via Krüppel-like transcription factor 6 promotes HuD expression in pancreatic β cell.Genes & diseases · 2024Article
- From Euglycemia to Recent Onset of Type 2 Diabetes Mellitus: A Proof-of-Concept Study on Circulating microRNA Profiling Reveals Distinct, and Early microRNA Signatures.Diagnostics (Basel, Switzerland) · 2023Article
- Pancreas-Liver-Adipose Axis: Target of Environmental Cadmium Exposure Linked to Metabolic Diseases.Toxics · 2023Review
- Lack of ZnT8 protects pancreatic islets from hypoxia- and cytokine-induced cell death.The Journal of endocrinology · 2022Article
- Zinc Homeostasis in Diabetes Mellitus and Vascular Complications.Biomedicines · 2022Review
- The Allelic Variant A391T of Metal Ion Transporter ZIP8 (SLC39A8) Leads to Hypotension and Enhanced Insulin Resistance.Frontiers in physiology · 2022Article
- Synchrotron fluorescence imaging of individual mouse beta-cells reveals changes in zinc, calcium, and iron in a model of low-grade inflammation.Metallomics : integrated biometal science · 2021Article
- Inside the Insulin Secretory Granule.Metabolites · 2021Review
- Loss of Znt8 function in diabetes mellitus: risk or benefit?Molecular and cellular biochemistry · 2021Review
- HIF-1α Dependent Upregulation of ZIP8, ZIP14, and TRPA1 Modify Intracellular ZnInternational journal of molecular sciences · 2021Article
5 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Zn²⁺ is an important cofactor for insulin biosynthesis and storage in pancreatic β-cells. Correspondingly, polymorphisms in the SLC30A8 gene, encoding the secretory granule Zn²⁺ transporter ZnT8, are associated with type 2 diabetes risk. Using a genetically engineered (FRET)-based sensor (eCALWY-4), we show here that elevated glucose time-dependently increases free cytosolic Zn²⁺ ([Zn²⁺](cyt)) in mouse pancreatic β-cells. These changes become highly significant (853 ± 96 pm versus 452 ± 42 pm, p < 0.001) after 24 h and are associated with increased expression of the Zn²⁺ importer family members Slc39a6, Slc39a7, and Slc39a8, and decreased expression of metallothionein 1 and 2. Arguing that altered expression of the above genes is not due to altered [Zn²⁺](cyt), elevation of extracellular (and intracellular) [Zn²⁺] failed to mimic the effects of high glucose. By contrast, increases in intracellular cAMP prompted by 3-isobutyl-1-methylxanthine and forskolin partially mimicked the effects of glucose on metallothionein, although not ZiP, gene expression. Modulation of intracellular Ca²⁺ and insulin secretion with pharmacological agents (tolbutamide and diazoxide) suggested a possible role for changes in these parameters in the regulation of Slc39a6 and Slc39a7 but not Slc39a8, nor metallothionein expression. In summary, 1) glucose induces increases in [Zn²⁺](cyt), which are then likely to facilitate the processing and/or the storage of insulin and its cocrystallization with Zn²⁺, and 2) these increases are associated with elevated expression of zinc importers. Conversely, a chronic increase in [Zn²⁺](cyt) following sustained hyperglycemia may contribute to β-cell dysfunction and death in some forms of diabetes.
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Registered trials
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