ReviewDiabetologia2015
SLC30A8 mutations in type 2 diabetes.
Review in Diabetologia, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
62 citing papers in PubMed, 2 syntheses or guidelines pooled it, 109 citations in OpenAlex.
- Genetic Variations as Modifying Factors to Dietary Zinc Requirements-A Systematic Review.Nutrients · 2017Pooled it
- Pooled it
- From Genes to Diets: A Critical Review of Genetic, Nutrigenomic and Epigenetic Mechanisms in Type 2 Diabetes Mellitus.Nutrients · 2026Review
- Article
- A loss of function variant inmedRxiv : the preprint server for health sciences · 2026Article
- Correlative imaging reveals metal dyshomeostasis and altered zinc coordination environments in a pre-clinical Type 2 diabetes model.Metallomics : integrated biometal science · 2026Article
- Zinc and Type 2 Diabetes: A Systematic Review with a Narrative Synthesis of Their Bidirectional Relationship and Clinical Perspectives for Personalized Nutritional Support.Diseases (Basel, Switzerland) · 2025Review
- 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
- Two GWAS Suggestive-SNVs in the Zinc Transporter 8 Gene Synergistically Influence Insulin Resistance in Type 2 Diabetes.International journal of preventive medicine · 2025Article
- 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
- Multiple genetic variants at thebioRxiv : the preprint server for biology · 2023Article
- Zinc and iron dynamics in human islet amyloid polypeptide-induced diabetes mouse model.Scientific reports · 2023Article
- Article
- Impact of anFrontiers in endocrinology · 2023Article
- Lack of ZnT8 protects pancreatic islets from hypoxia- and cytokine-induced cell death.The Journal of endocrinology · 2022Article
- Posttranscriptional Regulation of Insulin Resistance: Implications for Metabolic Diseases.Biomolecules · 2022Review
- Identification of key biomarkers in Angelman syndrome by a multi-cohort analysis.Frontiers in medicine · 2022Article
- Inside the Insulin Secretory Granule.Metabolites · 2021Review
- Pancreatic β cell-selective zinc transporter 8 insufficiency accelerates diabetes associated with islet amyloidosis.JCI insight · 2021Article
2 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
2 authors at 2 institutions in 2 countries.
Funding
Abstract
SLC30A8 encodes the secretory granule-resident and largely endocrine pancreas-restricted zinc transporter ZnT8. Interest in this gene product was sparked amongst diabetologists in 2007 when the first genome-wide association study for type 2 diabetes identified polymorphisms in SLC30A8 as affecting disease risk. Thus, the common polymorphism rs13266634 was associated with lowered beta cell function and a 14% increase in diabetes abundance per risk (C) allele. This non-synonymous variant encodes a tryptophan-to-arginine switch at position 325 in the protein's intracellular carboxy-terminal domain, resulting in reduced zinc transport activity and, consequently, decreased intragranular zinc levels. Whereas insulin secretion from isolated islets is most often increased in mice inactivated for Slc30a8, null animals usually show impaired glucose tolerance and lowered circulating insulin. Since Slc30a8 null animals display little, if any, zinc secretion from islets, the lower plasma insulin levels could be explained by increased hepatic clearance as a result of lowered local zinc levels, or less efficient insulin action on target tissues. Despite the emerging consensus on the role of ZnT8 in glucose homeostasis, a recent genetic study in humans has unexpectedly identified loss-of-function SLC30A8 mutants that are associated with protection from diabetes. Here, we attempt to reconcile these apparently contradictory findings, implicating (1) differing degrees of inhibition of ZnT8 activity in carriers of common variants vs rare loss-of-function forms, (2) effects dependent on age or hypoxic beta cell stress. We propose that these variables conspire to affect both the size and the direction of the effect of SLC30A8 risk alleles in man.
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What OpenQuestion holds
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.