Your browser has javascript turned off or blocked. This will lead to some parts of our website to not work properly or at all. Turn on javascript for best performance.

The browser you are using is not supported by this website. All versions of Internet Explorer are no longer supported, either by us or Microsoft (read more here: https://www.microsoft.com/en-us/microsoft-365/windows/end-of-ie-support).

Please use a modern browser to fully experience our website, such as the newest versions of Edge, Chrome, Firefox or Safari etc.

Hindrik Mulder

Hindrik Mulder

Principal investigator

Hindrik Mulder

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
  • Diabetes and Celiac Unit
  • Genomics, Diabetes and Endocrinology
  • Centre for Analysis and Synthesis
  • Biochemistry and Structural Biology
  • EXODIAB: Excellence in 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
  • Diabetes and Celiac Unit
  • Genomics, Diabetes and Endocrinology

ISBN/ISSN/Other

  • ISSN: 2041-1723