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Loss of ZnT8 functi...
Loss of ZnT8 function protects against diabetes by enhanced insulin secretion
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- Dwivedi, Om Prakash (author)
- University of Helsinki
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- Lehtovirta, Mikko (author)
- University of Helsinki
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- Hastoy, Benoit (author)
- University of Oxford
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- Chandra, Vikash (author)
- University of Helsinki
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- Krentz, Nicole A. J. (author)
- University of Oxford
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Kleiner, Sandra (author)
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- Jain, Deepak (author)
- Lund University,Lunds universitet,Antigen presentation,Forskargrupper vid Lunds universitet,Medicinsk proteinvetenskap,Antigen Presentation,Lund University Research Groups,Medical Protein Science
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- Richard, Ann-Marie (author)
- Pfizer Inc. US
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- Abaitua, Fernando (author)
- University of Oxford
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- Beer, Nicola L. (author)
- University of Oxford
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Grotz, Antje (author)
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- Prasad, Rashmi B. (author)
- Lund University,Lunds universitet,Translationell muskelforskning,Forskargrupper vid Lunds universitet,Translational Muscle Research,Lund University Research Groups,Skåne University Hospital
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- Hansson, Ola (author)
- Lund University,Lunds universitet,Translationell muskelforskning,Forskargrupper vid Lunds universitet,Translational Muscle Research,Lund University Research Groups,Skåne University Hospital,University of Helsinki
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- Ahlqvist, Emma (author)
- Lund University,Lunds universitet,Translationell muskelforskning,Forskargrupper vid Lunds universitet,Translational Muscle Research,Lund University Research Groups,Skåne University Hospital
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- Krus, Ulrika (author)
- Lund University,Lunds universitet,Diabetes - öpatofysiologi,Forskargrupper vid Lunds universitet,Diabetes - Islet Patophysiology,Lund University Research Groups
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- Artner, Isabella (author)
- Lund University,Lunds universitet,Stamcellscentrum (SCC),Avdelningen för stamcellsforskning,Institutionen för laboratoriemedicin,Medicinska fakulteten,Endokrin Celldifferentiering,Forskargrupper vid Lunds universitet,Stem Cell Center,Division of stem cell research,Department of Laboratory Medicine,Faculty of Medicine,Endocrine Cell Differentiation and Function,Lund University Research Groups,Skåne University Hospital
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Suoranta, Anu (author)
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Gomez, Daniel (author)
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Baras, Aris (author)
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Champon, Benoite (author)
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Payne, Anthony J. (author)
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Moralli, Daniela (author)
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Thomsen, Soren K. (author)
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Kramer, Philipp (author)
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Spiliotis, Ioannis (author)
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Ramracheya, Reshma (author)
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Chabosseau, Pauline (author)
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Theodoulou, Andria (author)
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Cheung, Rebecca (author)
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Van De Bunt, Martijn (author)
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- Flannick, Jason (author)
- Massachusetts General Hospital,Broad Institute
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- Trombetta, Maddalena (author)
- University of Verona
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Bonora, Enzo (author)
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- Wolheim, Claes B. (author)
- Lund University
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- Sarelin, Leena (author)
- Folkhälsan Research Center
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Bonadonna, Riccardo C. (author)
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- Rorsman, Patrik (author)
- University of Oxford
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Davies, Benjamin (author)
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Brosnan, Julia (author)
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Mccarthy, Mark I. (author)
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Otonkoski, Timo (author)
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- Lagerstedt, Jens O. (author)
- Lund University,Lunds universitet,Medicinsk proteinvetenskap,Forskargrupper vid Lunds universitet,Medical Protein Science,Lund University Research Groups
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Rutter, Guy A. (author)
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Gromada, Jesper (author)
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Gloyn, Anna L. (author)
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- Tuomi, Tiinamaija (author)
- Lund University,Lunds universitet,Translationell muskelforskning,Forskargrupper vid Lunds universitet,Translational Muscle Research,Lund University Research Groups
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- Groop, Leif (author)
- Lund University,Lunds universitet,Translationell muskelforskning,Forskargrupper vid Lunds universitet,Translational Muscle Research,Lund University Research Groups,University of Helsinki,Skåne University Hospital
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(creator_code:org_t)
- 2019-11-01
- 2019
- English.
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; , s. 1-22
- Related links:
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http://dx.doi.org/10...
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https://europepmc.or...
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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Abstract
Subject headings
Close
- 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 KATP channel function similar to isolated islets from carriers of the T2D-protective allele p.Trp325. These data position ZnT8 as an appealing target for treatment aimed at maintaining insulin secretion capacity in T2D.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Medical Genetics (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)
Publication and Content Type
- art (subject category)
- ref (subject category)
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- By the author/editor
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Dwivedi, Om Prak ...
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Lehtovirta, Mikk ...
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Hastoy, Benoit
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Chandra, Vikash
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Krentz, Nicole A ...
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Kleiner, Sandra
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show more...
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Jain, Deepak
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Richard, Ann-Mar ...
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Abaitua, Fernand ...
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Beer, Nicola L.
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Grotz, Antje
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Prasad, Rashmi B ...
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Hansson, Ola
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Ahlqvist, Emma
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Krus, Ulrika
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Artner, Isabella
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Suoranta, Anu
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Gomez, Daniel
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Baras, Aris
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Champon, Benoite
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Payne, Anthony J ...
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Moralli, Daniela
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Thomsen, Soren K ...
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Kramer, Philipp
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Spiliotis, Ioann ...
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Ramracheya, Resh ...
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Chabosseau, Paul ...
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Theodoulou, Andr ...
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Cheung, Rebecca
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Van De Bunt, Mar ...
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Flannick, Jason
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Trombetta, Madda ...
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Bonora, Enzo
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Wolheim, Claes B ...
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Sarelin, Leena
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Bonadonna, Ricca ...
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Rorsman, Patrik
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Davies, Benjamin
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Brosnan, Julia
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Mccarthy, Mark I ...
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Otonkoski, Timo
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Lagerstedt, Jens ...
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Rutter, Guy A.
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Gromada, Jesper
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Gloyn, Anna L.
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Tuomi, Tiinamaij ...
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Groop, Leif
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Medical Genetics
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Endocrinology an ...
- Articles in the publication
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Nature Genetics
- By the university
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Lund University