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

Research output: Contribution to journalArticle

Abstract

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.

Details

Authors
  • Taman Mahdi
  • Sonja Hänzelmann
  • Sarheed Jabar Muhammed
  • Thomas Reinbothe
  • Yunzhao Tang
  • Annika Axelsson
  • Yuedan Zhou
  • Xingjun Jing
  • Peter Almgren
  • Ulrika Krus
  • Jalal Taneera
  • Jonathan Derry
Organisations
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Cell and Molecular Biology
Original languageEnglish
Pages (from-to)625-633
JournalCell Metabolism
Volume16
Issue number5
Publication statusPublished - 2012
Publication categoryResearch
Peer-reviewedYes

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Related research output

Mahdi, T., 2013, Islet patophysiology. 138 p.

Research output: ThesisDoctoral Thesis (compilation)

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