ArticleDiabetes2009
Insulin storage and glucose homeostasis in mice null for the granule zinc transporter ZnT8 and studies of the type 2 diabetes-associated variants.
Article in Diabetes, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 224 papers, 8 of them syntheses that pooled it.
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Who cites it
224 citing papers in PubMed, 8 syntheses or guidelines pooled it.
- Association ofFrontiers in endocrinology · 2023Pooled it
- Association of type 2 diabetes susceptible genes GCKR, SLC30A8, and FTO polymorphisms with gestational diabetes mellitus risk: a meta-analysis.Endocrine · 2018Pooled it
- Pooled it
- Pooled it
- Association of SLC30A8 gene polymorphism with type 2 diabetes, evidence from 46 studies: a meta-analysis.Endocrine · 2016Pooled 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
- Genome-wide trans-ancestry meta-analysis provides insight into the genetic architecture of type 2 diabetes susceptibility.Nature genetics · 2014Pooled it
- Total zinc intake may modify the glucose-raising effect of a zinc transporter (SLC30A8) variant: a 14-cohort meta-analysis.Diabetes · 2011Pooled it
- A modality-aware CRISPR actionability framework for functional prioritization of genome-wide significant type 2 diabetes loci.Molecular genetics and genomics : MGG · 2026Article
- Zinc Homeostasis and the Risk of Type 2 Diabetes: Complex Role of ZnT8 in Insulin and Glucagon Secretion.Current nutrition reports · 2026Review
- A loss of function variant inmedRxiv : the preprint server for health sciences · 2026Article
- Molecular Genetics of β-Cell Compensation in Gestational Diabetes Mellitus: Insights from CDKAL1, SLC30A8 and HHEX.International journal of molecular sciences · 2026Review
- Complete loss of SLC30A8 in humans improves glucose metabolism and beta cell function.Diabetologia · 2025Article
- Effects of rs3802177 G/A polymorphism on SLC30A8 mRNA and hsa-miR-183-5p in Malay women with gestational diabetes mellitus.Scientific reports · 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
- The Islet-1 Interaction Partner Rnf20 Regulates Glucose Homeostasis and Pancreatic β-Cell Identity.Diabetes · 2025Article
- High Serum Zinc Concentration Accelerates Progression of Isolated Impaired Glucose Tolerance to Type 2 Diabetes: A Cohort Study.Biological trace element research · 2025Article
- Zrt-Irt-like Proteins (ZIP) Family Zinc Transporters: Emerging Players in Pancreatic β Cell Function and Insulin Regulation.The Journal of nutrition · 2025Review
- Zinc sulphate attenuates metabolic dysfunctions induced by olanzapine via the reduction of insulin resistance, hepatic oxidative stress, and inflammation in albino rats.BMC pharmacology & toxicology · 2025Article
164 more citing papers are in PubMed but not listed here.
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Authors and funding
33 authors.
Funding
Abstract
objectiveZinc ions are essential for the formation of hexameric insulin and hormone crystallization. A nonsynonymous single nucleotide polymorphism rs13266634 in the SLC30A8 gene, encoding the secretory granule zinc transporter ZnT8, is associated with type 2 diabetes. We describe the effects of deleting the ZnT8 gene in mice and explore the action of the at-risk allele. RESEARCH DESIGN AND
methodsSlc30a8 null mice were generated and backcrossed at least twice onto a C57BL/6J background. Glucose and insulin tolerance were measured by intraperitoneal injection or euglycemic clamp, respectively. Insulin secretion, electrophysiology, imaging, and the generation of adenoviruses encoding the low- (W325) or elevated- (R325) risk ZnT8 alleles were undertaken using standard protocols.
resultsZnT8(-/-) mice displayed age-, sex-, and diet-dependent abnormalities in glucose tolerance, insulin secretion, and body weight. Islets isolated from null mice had reduced granule zinc content and showed age-dependent changes in granule morphology, with markedly fewer dense cores but more rod-like crystals. Glucose-stimulated insulin secretion, granule fusion, and insulin crystal dissolution, assessed by total internal reflection fluorescence microscopy, were unchanged or enhanced in ZnT8(-/-) islets. Insulin processing was normal. Molecular modeling revealed that residue-325 was located at the interface between ZnT8 monomers. Correspondingly, the R325 variant displayed lower apparent Zn(2+) transport activity than W325 ZnT8 by fluorescence-based assay.
conclusionsZnT8 is required for normal insulin crystallization and insulin release in vivo but not, remarkably, in vitro. Defects in the former processes in carriers of the R allele may increase type 2 diabetes risks.
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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.