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Scientific article
Open access
English

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

Published inCell metabolism, vol. 16, no. 5, p. 625-633
Publication date2012
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.

Keywords
  • Animals
  • Calcium/metabolism
  • Calcium Channels/metabolism
  • Cells, Cultured
  • Diabetes Mellitus, Type 2/metabolism/pathology
  • Exocytosis
  • Gene Expression
  • Glucose/pharmacology
  • Hemoglobin A, Glycosylated/metabolism
  • Humans
  • Insulin/metabolism/secretion
  • Interleukin-1beta/metabolism
  • Islets of Langerhans/cytology/metabolism
  • Mice
  • Proto-Oncogene Proteins/antagonists & inhibitors/genetics/metabolism
  • RNA Interference
  • RNA, Small Interfering/metabolism
  • Signal Transduction
  • Wnt Proteins/metabolism
Citation (ISO format)
MAHDI, Taman et al. Secreted frizzled-related protein 4 reduces insulin secretion and is overexpressed in type 2 diabetes. In: Cell metabolism, 2012, vol. 16, n° 5, p. 625–633. doi: 10.1016/j.cmet.2012.10.009
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Article (Published version)
accessLevelPublic
Identifiers
ISSN of the journal1550-4131
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