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

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 WollheimLeif Groop, Erik Renström, Anders Rosengren

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskriftPeer review

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Sammanfattning

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.
Originalspråkengelska
Sidor (från-till)625-633
TidskriftCell Metabolism
Volym16
Nummer5
DOI
StatusPublished - 2012

Ämnesklassifikation (UKÄ)

  • Cell- och molekylärbiologi

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