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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 ; Jing, Xingjun ; Almgren, Peter ; Krus, Ulrika ; Taneera, Jalal ; Blom, Anna M. ; Lyssenko, Valeriya ; Esguerra, Jonathan Lou S. ; Hansson, Ola ; Eliasson, Lena ; Derry, Jonathan ; Zhang, Enming ; Wollheim, Claes B. ; Groop, Leif ; Renström, Erik ; Rosengren, Anders H.

Cell metabolism, 2012-11, Vol.16 (5), p.625-633 [Periódico revisado por pares]

United States: Elsevier Inc

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Título:
Secreted Frizzled-Related Protein 4 Reduces Insulin Secretion and Is Overexpressed in Type 2 Diabetes
Autor: Mahdi, Taman ; Hänzelmann, Sonja ; Salehi, Albert ; Muhammed, Sarheed J. ; Reinbothe, Thomas M. ; Tang, Yunzhao ; Axelsson, Annika S. ; Zhou, Yuedan ; Jing, Xingjun ; Almgren, Peter ; Krus, Ulrika ; Taneera, Jalal ; Blom, Anna M. ; Lyssenko, Valeriya ; Esguerra, Jonathan Lou S. ; Hansson, Ola ; Eliasson, Lena ; Derry, Jonathan ; Zhang, Enming ; Wollheim, Claes B. ; Groop, Leif ; Renström, Erik ; Rosengren, Anders H.
Assuntos: Animals ; Basic Medicine ; Calcium - metabolism ; Calcium Channels - metabolism ; Cell and Molecular Biology ; Cell- och molekylärbiologi ; Cells, Cultured ; Diabetes Mellitus, Type 2 - metabolism ; Diabetes Mellitus, Type 2 - pathology ; Exocytosis ; Gene Expression ; Glucose - pharmacology ; Glycated Hemoglobin A - metabolism ; Humans ; Insulin - metabolism ; Insulin Secretion ; Interleukin-1beta - metabolism ; Islets of Langerhans - cytology ; Islets of Langerhans - metabolism ; Medical and Health Sciences ; Medicin och hälsovetenskap ; Medicinska och farmaceutiska grundvetenskaper ; Mice ; Proto-Oncogene Proteins - antagonists & inhibitors ; Proto-Oncogene Proteins - genetics ; Proto-Oncogene Proteins - metabolism ; RNA Interference ; RNA, Small Interfering - metabolism ; Signal Transduction ; Wnt Proteins - metabolism
É parte de: Cell metabolism, 2012-11, Vol.16 (5), p.625-633
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SourceType-Scholarly Journals-1
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Descrição: 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 Ca2+ 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. [Display omitted] ▸ SFRP4 is a hub gene in a T2D-associated gene coexpression module in human islets ▸ SFRP4 reduces glucose-induced insulin secretion through decreased β cell exocytosis ▸ Expression and release of SFRP4 from islets is enhanced by interleukin-1β ▸ SFRP4 is elevated in serum several years before clinical diagnosis of T2D
Editor: United States: Elsevier Inc
Idioma: Inglês

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Secreted Frizzled-Related Protein 4 Reduces Insulin Secretion and Is Overexpressed in Type 2 Diabetes

United States: Elsevier Inc

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