ArticleNature genetics2019
Loss of ZnT8 function protects against diabetes by enhanced insulin secretion.
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Article in Nature genetics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 102 papers, 1 of them a synthesis that pooled it.
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102citing papers in PubMed, 1 pooled it
16.1field-weighted citation impact, top 1% of its field
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Who cites it
102 citing papers in PubMed, 1 synthesis or guideline pooled it, 146 citations in OpenAlex.
- TIGER: The gene expression regulatory variation landscape of human pancreatic islets.Cell reports · 2021Pooled it
- Article
- A functional missense variant iniScience · 2026Article
- A pangenome framework uncovers the role of deletions in repeated evolution of cave-derived traits.Genome research · 2026Article
- The central role of the β-cell in diabetes: from monogenic forms to type 1, type 2, and gestational diabetes.Reviews in endocrine & metabolic disorders · 2026Review
- Loss of Slc39a5 in α-cells impairs glucose metabolism by chronically increasing glucagon.Journal of advanced research · 2026Article
- Pancreatic organoids and organoid-on-a-chip platforms: from disease modeling to precision therapy.Journal of translational medicine · 2026Review
- To β or not to β: think zinc (again)!Cell research · 2026Article
- Zinc accumulation-induced integrated stress response triggers β-cell identity loss.Cell research · 2026Article
- A loss of function variant inmedRxiv : the preprint server for health sciences · 2026Article
- Zinc, type 2 diabetes, diabetic kidney disease: focus on hypoxia.Frontiers in endocrinology · 2026Review
- Molecular Portrait of Autoantigens in Type 1 Diabetes.Biomolecules · 2025Review
- 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
- 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
- High Serum Zinc Concentration Accelerates Progression of Isolated Impaired Glucose Tolerance to Type 2 Diabetes: A Cohort Study.Biological trace element research · 2025Article
- The role of the beta cell in type 2 diabetes: new findings from the last 5 years.Diabetologia · 2025Review
- The SLC-ome of membrane transport: From molecular discovery to physiology and clinical applications.Physiological reviews · 2025Review
- The role of protective genetic variants in modulating epigenetic aging.GeroScience · 2025Article
- Zrt-Irt-like Proteins (ZIP) Family Zinc Transporters: Emerging Players in Pancreatic β Cell Function and Insulin Regulation.The Journal of nutrition · 2025Review
42 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
47 authors at 12 institutions in 5 countries.
Om Prakash Dwivedi *Institute for Molecular Medicine Finland, Helsinki University, Helsinki, Finland.ORCID http://orcid.org/0000-0001-8670-7717
Mikko Lehtovirta *Institute for Molecular Medicine Finland, Helsinki University, Helsinki, Finland.
Benoit Hastoy *Oxford Centre for Diabetes Endocrinology and Metabolism, University of Oxford, Oxford, UK.ORCID http://orcid.org/0000-0003-1244-7857
Vikash ChandraStem Cells and Metabolism Research Program and Biomedicum Stem Cell Centre, Faculty of Medicine, University of Helsinki, Helsinki, Finland.ORCID http://orcid.org/0000-0002-2713-1831
Nicole A J KrentzWellcome Centre for Human Genetics, University of Oxford, Oxford, UK.ORCID http://orcid.org/0000-0003-3622-2652
Sandra KleinerRegeneron Pharmaceuticals, Tarrytown, NY, USA.
Deepak JainDepartment of Experimental Medical Science, Lund University, Lund, Sweden.
Ann-Marie RichardPfizer Inc., Cambridge, MA, USA.
Fernando AbaituaWellcome Centre for Human Genetics, University of Oxford, Oxford, UK.
Nicola L BeerOxford Centre for Diabetes Endocrinology and Metabolism, University of Oxford, Oxford, UK.
Antje GrotzOxford Centre for Diabetes Endocrinology and Metabolism, University of Oxford, Oxford, UK.ORCID http://orcid.org/0000-0002-7736-510X
Rashmi B PrasadLund University Diabetes Centre, Department of Clinical Sciences, Lund University, Skåne University Hospital, Malmö, Sweden.ORCID http://orcid.org/0000-0002-4400-6741
Ola HanssonInstitute for Molecular Medicine Finland, Helsinki University, Helsinki, Finland.ORCID http://orcid.org/0000-0002-7394-7639
Emma AhlqvistLund University Diabetes Centre, Department of Clinical Sciences, Lund University, Skåne University Hospital, Malmö, Sweden.ORCID http://orcid.org/0000-0002-6513-2384
Ulrika KrusLund University Diabetes Centre, Department of Clinical Sciences, Lund University, Skåne University Hospital, Malmö, Sweden.
Isabella ArtnerLund University Diabetes Centre, Department of Clinical Sciences, Lund University, Skåne University Hospital, Malmö, Sweden.ORCID http://orcid.org/0000-0002-2895-5664
Anu SuorantaInstitute for Molecular Medicine Finland, Helsinki University, Helsinki, Finland.
Daniel GomezRegeneron Pharmaceuticals, Tarrytown, NY, USA.
Aris BarasRegeneron Pharmaceuticals, Tarrytown, NY, USA.ORCID http://orcid.org/0000-0002-6830-3396
Benoite ChamponWellcome Centre for Human Genetics, University of Oxford, Oxford, UK.
Anthony J PayneWellcome Centre for Human Genetics, University of Oxford, Oxford, UK.
Daniela MoralliWellcome Centre for Human Genetics, University of Oxford, Oxford, UK.ORCID http://orcid.org/0000-0001-7977-8496
Soren K ThomsenOxford Centre for Diabetes Endocrinology and Metabolism, University of Oxford, Oxford, UK.
Philipp KramerWellcome Centre for Human Genetics, University of Oxford, Oxford, UK.
Ioannis SpiliotisOxford Centre for Diabetes Endocrinology and Metabolism, University of Oxford, Oxford, UK.ORCID http://orcid.org/0000-0003-4171-9612
Reshma RamracheyaOxford Centre for Diabetes Endocrinology and Metabolism, University of Oxford, Oxford, UK.
Pauline ChabosseauSection of Cell Biology, Department of Medicine, Imperial College London, Imperial Centre for Translational and Experimental Medicine, Hammersmith, Hospital, London, UK.
Andria TheodoulouSection of Cell Biology, Department of Medicine, Imperial College London, Imperial Centre for Translational and Experimental Medicine, Hammersmith, Hospital, London, UK.
Rebecca CheungSection of Cell Biology, Department of Medicine, Imperial College London, Imperial Centre for Translational and Experimental Medicine, Hammersmith, Hospital, London, UK.
Martijn van de BuntOxford Centre for Diabetes Endocrinology and Metabolism, University of Oxford, Oxford, UK.
Jason FlannickDepartment of Molecular Biology, Massachusetts General Hospital, Boston, MA, USA.
Maddalena TrombettaDepartment of Medicine, University of Verona and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy.
Enzo BonoraDepartment of Medicine, University of Verona and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy.
Claes B WolheimLund University Diabetes Centre, Department of Clinical Sciences, Lund University, Skåne University Hospital, Malmö, Sweden.
Leena SarelinFolkhälsan Research Center, Helsinki, Finland.
Riccardo C BonadonnaDepartment of Medicine and Surgery, University of Parma School of Medicine and Azienda Ospedaliera Universitaria of Parma, Parma, Italy.
Patrik RorsmanOxford Centre for Diabetes Endocrinology and Metabolism, University of Oxford, Oxford, UK.ORCID http://orcid.org/0000-0001-7578-0767
Benjamin DaviesWellcome Centre for Human Genetics, University of Oxford, Oxford, UK.ORCID http://orcid.org/0000-0003-3623-600X
Julia BrosnanPfizer Inc., Cambridge, MA, USA.
Mark I McCarthyOxford Centre for Diabetes Endocrinology and Metabolism, University of Oxford, Oxford, UK.ORCID http://orcid.org/0000-0002-4393-0510
Timo OtonkoskiStem Cells and Metabolism Research Program and Biomedicum Stem Cell Centre, Faculty of Medicine, University of Helsinki, Helsinki, Finland.ORCID http://orcid.org/0000-0001-9190-2496
Jens O LagerstedtDepartment of Experimental Medical Science, Lund University, Lund, Sweden.
Guy A RutterSection of Cell Biology, Department of Medicine, Imperial College London, Imperial Centre for Translational and Experimental Medicine, Hammersmith, Hospital, London, UK.ORCID http://orcid.org/0000-0001-6360-0343
Jesper GromadaRegeneron Pharmaceuticals, Tarrytown, NY, USA.
Anna L GloynOxford Centre for Diabetes Endocrinology and Metabolism, University of Oxford, Oxford, UK.ORCID http://orcid.org/0000-0003-1205-1844
Tiinamaija TuomiInstitute for Molecular Medicine Finland, Helsinki University, Helsinki, Finland.ORCID http://orcid.org/0000-0002-8306-6202
Leif GroopInstitute for Molecular Medicine Finland, Helsinki University, Helsinki, Finland. Leif.Groop@helsinki.fi.ORCID http://orcid.org/0000-0002-0187-3263
Centre for Human Genetics · GBLund University · SEUniversity of Oxford · GBHammersmith Hospital · GBRegeneron (United States) · USInstitute for Molecular Medicine Finland · FIUniversity of Helsinki · FIPfizer (United States) · USUniversity of Verona · ITBroad Institute · USFolkhälsans Forskningscentrum · FIUniversity of Parma · IT
Funding
Identifying variants causal for Type 2 Diabetes in Major human populationsU01DK085545 · NIDDK · UNIVERSITY OF OXFORD · PI CHAN, JULIANA CN, EBRAHIM, SHAH BRIAN · 2009 to 2013
$2.8MIntegrating genome-scale data to reveal causal mechanisms in type 2 diabetesU01DK105535 · NIDDK · UNIVERSITY OF OXFORD · PI GLOYN, ANNA LOUISE · 2015 to 2019
$1.7MMedical Research Council G0801995Medical Research Council MR/K001981/1Medical Research Council MR/K023667/1Medical Research Council MR/L020149/1Medical Research Council MR/L02036X/1Medical Research Council MR/M012646/1Medical Research Council MR/N00275X/1Medical Research Council MR/N020472/1Medical Research Council MR/R010676/1Medical Research Council MR/R022259/1NIDDK NIH HHS U01 DK085545NIDDK NIH HHS U01 DK105535Wellcome Trust 095101Wellcome Trust 200837Wellcome Trust 200837/Z/16/ZWellcome Trust 203141
Abstract
A rare loss-of-function allele p.Arg138* in SLC30A8 encoding the zinc transporter 8 (ZnT8), which is enriched in Western Finland, protects against type 2 diabetes (T2D). We recruited relatives of the identified carriers and showed that protection was associated with better insulin secretion due to enhanced glucose responsiveness and proinsulin conversion, particularly when compared with individuals matched for the genotype of a common T2D-risk allele in SLC30A8, p.Arg325. In genome-edited human induced pluripotent stem cell (iPSC)-derived β-like cells, we establish that the p.Arg138* allele results in reduced SLC30A8 expression due to haploinsufficiency. In human β cells, loss of SLC30A8 leads to increased glucose responsiveness and reduced K
Indexed as
Insulin SecretionAdolescentAdultAgedDiabetes Mellitus, Type 2FemaleGenotypeGlucoseHumansInduced Pluripotent Stem CellsIslets of LangerhansMaleMiddle AgedYoung AdultZinc Transporter 8GlucoseSLC30A8 protein, humanZinc Transporter 8
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