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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
Publishing year: 2012
Language: English
Pages: 625-633
Publication/Series: Cell Metabolism
Volume: 16
Issue: 5
Document type: Journal article
Publisher: Cell Press

Abstract 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.

Keywords

  • Cell and Molecular Biology

Other

Published
  • Islet patophysiology
  • Islet cell physiology
  • Diabetes and Endocrinology
  • Protein Chemistry, Malmö
  • Islet cell exocytosis
  • ISSN: 1550-4131
Erik Renström
E-mail: erik [dot] renstrom [at] med [dot] lu [dot] se

Deputy head of department

Department of Clinical Sciences, Malmö

+46 40 39 11 57

+46 40 39 11 57

Principal investigator

Islet patophysiology

+46 40 39 11 57

+46 40 39 11 57

20-3-308

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Lund University Diabetes Centre, CRC, SUS Malmö, Entrance 72, House 91:12. SE-205 02 Malmö. Telephone: +46 40 39 10 00