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.

Ola Hansson

Ola Hansson

Principal investigator

Ola Hansson

Secreted frizzled-related protein 4 reduces insulin secretion and is overexpressed in type 2 diabetes.

Author

  • Taman Mahdi
  • Sonja Hänzelmann
  • S Albert Salehi
  • Sarheed Jabar Muhammed
  • Thomas Reinbothe
  • Yunzhao Tang
  • Annika Axelsson
  • Yuedan Zhou
  • Xingjun Jing
  • Peter Almgren
  • Ulrika Krus
  • Jalal Taneera
  • Anna Blom
  • Valeriya Lyssenko
  • Jonathan Esguerra
  • Ola Hansson
  • Lena Eliasson
  • Jonathan Derry
  • Enming Zhang
  • Claes Wollheim
  • Leif Groop
  • Erik Renström
  • Anders Rosengren

Summary, in English

A plethora of candidate genes have been identified for complex polygenic disorders, but the underlying disease mechanisms remain largely unknown. We explored the pathophysiology of type 2 diabetes (T2D) by analyzing global gene expression in human pancreatic islets. A group of coexpressed genes (module), enriched for interleukin-1-related genes, was associated with T2D and reduced insulin secretion. One of the module genes that was highly overexpressed in islets from T2D patients is SFRP4, which encodes secreted frizzled-related protein 4. SFRP4 expression correlated with inflammatory markers, and its release from islets was stimulated by interleukin-1β. Elevated systemic SFRP4 caused reduced glucose tolerance through decreased islet expression of Ca(2+) channels and suppressed insulin exocytosis. SFRP4 thus provides a link between islet inflammation and impaired insulin secretion. Moreover, the protein was increased in serum from T2D patients several years before the diagnosis, suggesting that SFRP4 could be a potential biomarker for islet dysfunction in T2D.

Department/s

  • Diabetes - Islet Patophysiology
  • Islet cell physiology
  • Genomics, Diabetes and Endocrinology
  • Protein Chemistry, Malmö
  • Diabetes - Islet Cell Exocytosis
  • EXODIAB: Excellence of Diabetes Research in Sweden
  • EpiHealth: Epidemiology for Health

Publishing year

2012

Language

English

Pages

625-633

Publication/Series

Cell Metabolism

Volume

16

Issue

5

Document type

Journal article

Publisher

Cell Press

Topic

  • Cell and Molecular Biology

Status

Published

Research group

  • Diabetes - Islet Patophysiology
  • Islet cell physiology
  • Genomics, Diabetes and Endocrinology
  • Protein Chemistry, Malmö
  • Diabetes - Islet Cell Exocytosis

ISBN/ISSN/Other

  • ISSN: 1550-4131