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Leif Groop

Leif Groop

Principal investigator

Leif Groop

Loss of ZnT8 function protects against diabetes by enhanced insulin secretion


  • Om Prakash Dwivedi
  • Mikko Lehtovirta
  • Benoit Hastoy
  • Vikash Chandra
  • Nicole A. J. Krentz
  • Sandra Kleiner
  • Deepak Jain
  • Ann-Marie Richard
  • Fernando Abaitua
  • Nicola L. Beer
  • Antje Grotz
  • Rashmi B. Prasad
  • Ola Hansson
  • Emma Ahlqvist
  • Ulrika Krus
  • Isabella Artner
  • Anu Suoranta
  • Daniel Gomez
  • Aris Baras
  • Benoite Champon
  • Anthony J. Payne
  • Daniela Moralli
  • Soren K. Thomsen
  • Philipp Kramer
  • Ioannis Spiliotis
  • Reshma Ramracheya
  • Pauline Chabosseau
  • Andria Theodoulou
  • Rebecca Cheung
  • Martijn Van De Bunt
  • Jason Flannick
  • Maddalena Trombetta
  • Enzo Bonora
  • Claes B. Wolheim
  • Leena Sarelin
  • Riccardo C. Bonadonna
  • Patrik Rorsman
  • Benjamin Davies
  • Julia Brosnan
  • Mark I. Mccarthy
  • Timo Otonkoski
  • Jens O. Lagerstedt
  • Guy A. Rutter
  • Jesper Gromada
  • Anna L. Gloyn
  • Tiinamaija Tuomi
  • Leif Groop

Summary, in English

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.


  • Antigen Presentation
  • Medical Protein Science
  • EXODIAB: Excellence of Diabetes Research in Sweden
  • Genomics, Diabetes and Endocrinology
  • Diabetes - Islet Patophysiology
  • Endocrine Cell Differentiation and Function
  • StemTherapy: National Initiative on Stem Cells for Regenerative Therapy
  • Stem Cell Center

Publishing year







Nature Genetics

Document type

Journal article


Nature Publishing Group


  • Medical Genetics
  • Endocrinology and Diabetes



Research group

  • Antigen Presentation
  • Medical Protein Science
  • Genomics, Diabetes and Endocrinology
  • Diabetes - Islet Patophysiology
  • Endocrine Cell Differentiation and Function


  • ISSN: 1061-4036