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Cell Metab. 2012 Nov 7;16(5):625-33. doi: 10.1016/j.cmet.2012.10.009.

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

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1
Lund University Diabetes Centre, Lund University, 20502 Malmö, Sweden.

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.

PMID:
23140642
DOI:
10.1016/j.cmet.2012.10.009
[Indexed for MEDLINE]
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