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.

• Författare: 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
• Avdelning/ar: Diabetes - öpatofysiologi; Islet cell physiology; Translationell Muskel Forskning; Proteinkemi, Malmö; Diabetes - öcellsexocytos; EXODIAB: Excellence of Diabetes Research in Sweden; EpiHealth: Epidemiology for Health
• Publiceringsår: 2012
• Språk: Engelska
• Sidor: 625-633
• Publikation/Tidskrift/Serie: Cell Metabolism
• Volym: 16
• Issue: 5
• Fulltext: - 8 MB; Download statistics
• Länkar: http://www.ncbi.nlm.nih.gov/pubmed/23140642?dopt=Abstract; http://dx.doi.org/10.1016/j.cmet.2012.10.009
• Dokumenttyp: Artikel i tidskrift
• Förlag: Cell Press
• Ämne: Cell and Molecular Biology
• Status: Published
• Forskningsgrupp: Diabetes - Islet Patophysiology; Islet cell physiology; Genomics, Diabetes and Endocrinology; Protein Chemistry, Malmö; Diabetes - Islet Cell Exocytosis
• ISBN/ISSN/Övrigt: ISSN: 1550-4131