ArticleThe Journal of biological chemistry2015
Characterization of Zinc Influx Transporters (ZIPs) in Pancreatic β Cells: ROLES IN REGULATING CYTOSOLIC ZINC HOMEOSTASIS AND INSULIN SECRETION.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers, 1 of them a synthesis that pooled it.
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Who cites it
46 citing papers in PubMed, 1 synthesis or guideline pooled it, 73 citations in OpenAlex.
- Expression of the ZIP/SLC39A transporters in β-cells: a systematic review and integration of multiple datasets.BMC genomics · 2017Pooled it
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- Zinc, type 2 diabetes, diabetic kidney disease: focus on hypoxia.Frontiers in endocrinology · 2026Review
- Type 2 diabetes mellitus and zinc dysregulation: From basic and epidemiological evidence to interventions.Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS) · 2025Review
- Zrt-Irt-like Proteins (ZIP) Family Zinc Transporters: Emerging Players in Pancreatic β Cell Function and Insulin Regulation.The Journal of nutrition · 2025Review
- Genomics reveals eleven obesity endotypes with distinct biological and phenotypic signatures.medRxiv : the preprint server for health sciences · 2025Article
- Managing cardiovascular events, hyperglycemia, and obesity in type 2 diabetes through microRNA regulation linked to glucagon-like peptide-1 receptor agonists.Diabetology & metabolic syndrome · 2025Review
- 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 Impact on the Function of the Testicle and Epididymis.International journal of molecular sciences · 2024Review
- T-Cell Receptor Sequences Identify Combined Coxsackievirus-International journal of molecular sciences · 2024Article
- Cellular zinc metabolism and zinc signaling: from biological functions to diseases and therapeutic targets.Signal transduction and targeted therapy · 2024Review
- Absence ofAmerican journal of physiology. Endocrinology and metabolism · 2024Article
- Article
- 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
- Preparation and hypoglycemic effects of chromium- and zinc-richWorld journal of diabetes · 2022Article
- Zinc Homeostasis in Diabetes Mellitus and Vascular Complications.Biomedicines · 2022Review
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- The Association between Zinc and Copper Circulating Levels and Cardiometabolic Risk Factors in Adults: A Study of Qatar Biobank Data.Nutrients · 2021Article
- Elevated expression of the adhesion GPCR ADGRL4/ELTD1 promotes endothelial sprouting angiogenesis without activating canonical GPCR signalling.Scientific reports · 2021Article
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Authors and funding
13 authors at 1 institution in 1 country.
Funding
Abstract
Zinc plays an essential role in the regulation of pancreatic β cell function, affecting important processes including insulin biosynthesis, glucose-stimulated insulin secretion, and cell viability. Mutations in the zinc efflux transport protein ZnT8 have been linked with both type 1 and type 2 diabetes, further supporting an important role for zinc in glucose homeostasis. However, very little is known about how cytosolic zinc is controlled by zinc influx transporters (ZIPs). In this study, we examined the β cell and islet ZIP transcriptome and show consistent high expression of ZIP6 (Slc39a6) and ZIP7 (Slc39a7) genes across human and mouse islets and MIN6 β cells. Modulation of ZIP6 and ZIP7 expression significantly altered cytosolic zinc influx in pancreatic β cells, indicating an important role for ZIP6 and ZIP7 in regulating cellular zinc homeostasis. Functionally, this dysregulated cytosolic zinc homeostasis led to impaired insulin secretion. In parallel studies, we identified both ZIP6 and ZIP7 as potential interacting proteins with GLP-1R by a membrane yeast two-hybrid assay. Knock-down of ZIP6 but not ZIP7 in MIN6 β cells impaired the protective effects of GLP-1 on fatty acid-induced cell apoptosis, possibly via reduced activation of the p-ERK pathway. Therefore, our data suggest that ZIP6 and ZIP7 function as two important zinc influx transporters to regulate cytosolic zinc concentrations and insulin secretion in β cells. In particular, ZIP6 is also capable of directly interacting with GLP-1R to facilitate the protective effect of GLP-1 on β cell survival.
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