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

Mahdi, Taman
Hänzelmann, Sonja
Salehi, Albert
Muhammed, Sarheed J
Reinbothe, Thomas M
Tang, Yunzhao
Axelsson, Annika S
Zhou, Yuedan
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Published in Cell metabolism. 2012, vol. 16, no. 5, p. 625-33
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 AnimalsCalcium/metabolismCalcium Channels/metabolismCells, CulturedDiabetes Mellitus, Type 2/metabolism/pathologyExocytosisGene ExpressionGlucose/pharmacologyHemoglobin A, Glycosylated/metabolismHumansInsulin/metabolism/secretionInterleukin-1beta/metabolismIslets of Langerhans/cytology/metabolismMiceProto-Oncogene Proteins/antagonists & inhibitors/genetics/metabolismRNA InterferenceRNA, Small Interfering/metabolismSignal TransductionWnt Proteins/metabolism
PMID: 23140642
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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. 625-33. doi: 10.1016/j.cmet.2012.10.009 https://archive-ouverte.unige.ch/unige:33352

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Deposited on : 2014-01-16

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