ArticleThe Journal of biological chemistry2015
The Zinc Transporter Slc30a8/ZnT8 Is Required in a Subpopulation of Pancreatic α-Cells for Hypoglycemia-induced Glucagon 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 39 papers.
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Who cites it
39 citing papers in PubMed, 54 citations in OpenAlex.
- Loss of Slc39a5 in α-cells impairs glucose metabolism by chronically increasing glucagon.Journal of advanced research · 2026Article
- Rethinking Zinc Requirements in Diabetes Mellitus: Comprehensive Review of Experimental and Clinical Studies Evidence.Biological trace element research · 2026Review
- Zinc Homeostasis and the Risk of Type 2 Diabetes: Complex Role of ZnT8 in Insulin and Glucagon Secretion.Current nutrition reports · 2026Review
- Correlative imaging reveals metal dyshomeostasis and altered zinc coordination environments in a pre-clinical Type 2 diabetes model.Metallomics : integrated biometal science · 2026Article
- Complete loss of SLC30A8 in humans improves glucose metabolism and beta cell function.Diabetologia · 2025Article
- Sex-Specific Association Between Serum Zinc Concentration and Risk of Developing Type 2 Diabetes in Individuals with Isolated Impaired Fasting Glucose: A Prospective Cohort.Biological trace element research · 2025Article
- Association of serum zinc concentration with multiple surrogates of insulin resistance in a population-based study.Scientific reports · 2025Article
- Human pancreatic α-cell heterogeneity and trajectory inference analyses reveal SMOC1 as a β-cell dedifferentiation gene.Nature communications · 2025Article
- High Serum Zinc Concentration Accelerates Progression of Isolated Impaired Glucose Tolerance to Type 2 Diabetes: A Cohort Study.Biological trace element research · 2025Article
- Islet hormones at the intersection of glucose and amino acid metabolism.Nature reviews. Endocrinology · 2025Review
- A double knockout for zinc transporter 8 and somatostatin in mice reveals their distinct roles in regulation of insulin secretion and obesity.Genes & nutrition · 2024Article
- Identifying miRNA Signatures Associated with Pancreatic Islet Dysfunction in a FOXA2-Deficient iPSC Model.Stem cell reviews and reports · 2024Article
- Impact of anFrontiers in endocrinology · 2023Article
- Lack of ZnT8 protects pancreatic islets from hypoxia- and cytokine-induced cell death.The Journal of endocrinology · 2022Article
- Loss of Znt8 function in diabetes mellitus: risk or benefit?Molecular and cellular biochemistry · 2021Review
- Mitogen Synergy: An Emerging Route to Boosting Human Beta Cell Proliferation.Frontiers in cell and developmental biology · 2021Review
- Pathways of Glucagon Secretion and Trafficking in the Pancreatic Alpha Cell: Novel Pathways, Proteins, and Targets for Hyperglucagonemia.Frontiers in endocrinology · 2021Review
- Zinc.Advances in food and nutrition research · 2021Review
- A 3D culture platform enables development of zinc-binding prodrugs for targeted proliferation of β cells.Science advances · 2020Article
- ZIGIR, a Granule-Specific ZnCell reports · 2020Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
Abstract
SLC30A8 encodes a zinc transporter ZnT8 largely restricted to pancreatic islet β- and α-cells, and responsible for zinc accumulation into secretory granules. Although common SLC30A8 variants, believed to reduce ZnT8 activity, increase type 2 diabetes risk in humans, rare inactivating mutations are protective. To investigate the role of Slc30a8 in the control of glucagon secretion, Slc30a8 was inactivated selectively in α-cells by crossing mice with alleles floxed at exon 1 to animals expressing Cre recombinase under the pre-proglucagon promoter. Further crossing to Rosa26:tdRFP mice, and sorting of RFP(+): glucagon(+) cells from KO mice, revealed recombination in ∼ 30% of α-cells, of which ∼ 50% were ZnT8-negative (14 ± 1.8% of all α-cells). Although glucose and insulin tolerance were normal, female αZnT8KO mice required lower glucose infusion rates during hypoglycemic clamps and displayed enhanced glucagon release (p < 0.001) versus WT mice. Correspondingly, islets isolated from αZnT8KO mice secreted more glucagon at 1 mm glucose, but not 17 mm glucose, than WT controls (n = 5; p = 0.008). Although the expression of other ZnT family members was unchanged, cytoplasmic (n = 4 mice per genotype; p < 0.0001) and granular (n = 3, p < 0.01) free Zn(2+) levels were significantly lower in KO α-cells versus control cells. In response to low glucose, the amplitude and frequency of intracellular Ca(2+) increases were unchanged in α-cells of αZnT8KO KO mice. ZnT8 is thus important in a subset of α-cells for normal responses to hypoglycemia and acts via Ca(2+)-independent mechanisms.
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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.