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

Summary, in 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.

• 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
• Department/s: Diabetes - Islet Patophysiology; Islet cell physiology; Translational Muscle Research; Protein Chemistry, Malmö; Diabetes - Islet Cell Exocytosis; EXODIAB: Excellence of Diabetes Research in Sweden; EpiHealth: Epidemiology for Health
• Publishing year: 2012
• Language: English
• Pages: 625-633
• Publication/Series: Cell Metabolism
• Volume: 16
• Issue: 5
• Full text: - 8 MB; Download statistics
• Links: http://www.ncbi.nlm.nih.gov/pubmed/23140642?dopt=Abstract; http://dx.doi.org/10.1016/j.cmet.2012.10.009
• Document type: Journal article
• Publisher: Cell Press
• Topic: Cell and Molecular Biology
• Status: Published
• Research group: Diabetes - Islet Patophysiology; Islet cell physiology; Genomics, Diabetes and Endocrinology; Protein Chemistry, Malmö; Diabetes - Islet Cell Exocytosis
• ISBN/ISSN/Other: ISSN: 1550-4131