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ludc web

Anna Wendt

Assistant researcher

ludc web

Sox5 regulates beta-cell phenotype and is reduced in type 2 diabetes

Author

  • Annika Axelsson
  • T Mahdi
  • H A Nenonen
  • Tania Singh
  • S Hänzelmann
  • A Wendt
  • Annika Bagge
  • T M Reinbothe
  • J Millstein
  • X Yang
  • B. Zhang
  • E G Gusmao
  • L Shu
  • M Szabat
  • Y Tang
  • Jinling Wang
  • Sofia Salö
  • L Eliasson
  • I Artner
  • M Fex
  • J D Johnson
  • C B Wollheim
  • J M J Derry
  • B Mecham
  • P Spégel
  • H Mulder
  • Ivan G Costa
  • E Zhang
  • A H Rosengren

Summary, in English

Type 2 diabetes (T2D) is characterized by insulin resistance and impaired insulin secretion, but the mechanisms underlying insulin secretion failure are not completely understood. Here, we show that a set of co-expressed genes, which is enriched for genes with islet-selective open chromatin, is associated with T2D. These genes are perturbed in T2D and have a similar expression pattern to that of dedifferentiated islets. We identify Sox5 as a regulator of the module. Sox5 knockdown induces gene expression changes similar to those observed in T2D and diabetic animals and has profound effects on insulin secretion, including reduced depolarization-evoked Ca(2+)-influx and β-cell exocytosis. SOX5 overexpression reverses the expression perturbations observed in a mouse model of T2D, increases the expression of key β-cell genes and improves glucose-stimulated insulin secretion in human islets from donors with T2D. We suggest that human islets in T2D display changes reminiscent of dedifferentiation and highlight SOX5 as a regulator of β-cell phenotype and function.

Department/s

  • Diabetes - Islet Patophysiology
  • Stem Cell Center
  • Diabetes - Islet Cell Exocytosis
  • Diabetes - Molecular Metabolism
  • Celiac Disease and Diabetes Unit
  • Genomics, Diabetes and Endocrinology
  • Centre for Analysis and Synthesis
  • Biochemistry and Structural Biology
  • EXODIAB: Excellence of Diabetes Research in Sweden
  • StemTherapy: National Initiative on Stem Cells for Regenerative Therapy

Publishing year

2017-06-06

Language

English

Pages

15652-15652

Publication/Series

Nature Communications

Volume

8

Document type

Journal article

Publisher

Nature Publishing Group

Topic

  • Endocrinology and Diabetes

Keywords

  • Journal Article

Status

Published

Research group

  • Diabetes - Islet Patophysiology
  • Diabetes - Islet Cell Exocytosis
  • Diabetes - Molecular Metabolism
  • Celiac Disease and Diabetes Unit
  • Genomics, Diabetes and Endocrinology

ISBN/ISSN/Other

  • ISSN: 2041-1723