ArticleProceedings of the National Academy of Sciences of the United States of America2009
Insulin crystallization depends on zinc transporter ZnT8 expression, but is not required for normal glucose homeostasis in mice.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 180 papers, 2 of them syntheses that pooled it.
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Who cites it
180 citing papers in PubMed, 2 syntheses or guidelines pooled it, 328 citations in OpenAlex.
- Pooled it
- Association between SLC30A8 rs13266634 Polymorphism and Type 2 Diabetes Risk: A Meta-Analysis.Medical science monitor : international medical journal of experimental and clinical research · 2015Pooled it
- Article
- Article
- The SLC-ome of membrane transport: from molecular discovery to physiology and clinical applications.Physiological reviews · 2026Review
- SLC30A8 (ZnT8) at the crossroads of epigenetics and microRNA regulation in type 2 diabetes and nephropathy.World journal of nephrology · 2026Review
- Islet ultrastructure: past achievements and future directions.Diabetologia · 2026Review
- Zinc as a master regulator of intracellular organelle homeostasis.Experimental & molecular medicine · 2026Review
- Zinc Homeostasis and the Risk of Type 2 Diabetes: Complex Role of ZnT8 in Insulin and Glucagon Secretion.Current nutrition reports · 2026Review
- Complete loss of SLC30A8 in humans improves glucose metabolism and beta cell function.Diabetologia · 2025Article
- Association of serum zinc concentration with multiple surrogates of insulin resistance in a population-based study.Scientific reports · 2025Article
- 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
- Demixing of four simultaneously co-expressed phase-separating proteins in the endoplasmic reticulum lumen.Bioscience reports · 2025Article
- Shared transcriptional regulators and network rewiring identify therapeutic targets linking type 2 diabetes mellitus and hypertension.Frontiers in molecular biosciences · 2025Article
- Roles of zinc and zinc transporters in development, progression, and treatment of inflammatory bowel disease (IBD).Frontiers in nutrition · 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
- Understanding the Genetic Landscape of Gestational Diabetes: Insights into the Causes and Consequences of Elevated Glucose Levels in Pregnancy.Metabolites · 2024Review
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- Multiple genetic variants at the SLC30A8 locus affect local super-enhancer activity and influence pancreatic β-cell survival and function.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024Article
- Cellular zinc metabolism and zinc signaling: from biological functions to diseases and therapeutic targets.Signal transduction and targeted therapy · 2024Review
120 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 6 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Zinc co-crystallizes with insulin in dense core secretory granules, but its role in insulin biosynthesis, storage and secretion is unknown. In this study we assessed the role of the zinc transporter ZnT8 using ZnT8-knockout (ZnT8(-/-)) mice. Absence of ZnT8 expression caused loss of zinc release upon stimulation of exocytosis, but normal rates of insulin biosynthesis, normal insulin content and preserved glucose-induced insulin release. Ultrastructurally, mature dense core insulin granules were rare in ZnT8(-/-) beta cells and were replaced by immature, pale insulin "progranules," which were larger than in ZnT8(+/+) islets. When mice were fed a control diet, glucose tolerance and insulin sensitivity were normal. However, after high-fat diet feeding, the ZnT8(-/-) mice became glucose intolerant or diabetic, and islets became less responsive to glucose. Our data show that the ZnT8 transporter is essential for the formation of insulin crystals in beta cells, contributing to the packaging efficiency of stored insulin. Interaction between the ZnT8(-/-) genotype and diet to induce diabetes is a model for further studies of the mechanism of disease of human ZNT8 gene mutations.
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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.