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

Mahdi, Taman LU ; Hänzelmann, Sonja LU ; Salehi, S Albert LU ; Jabar Muhammed, Sarheed LU ; Reinbothe, Thomas LU ; Tang, Yunzhao LU ; Axelsson, Annika LU ; Zhou, Yuedan LU ; Jing, Xingjun and Almgren, Peter LU , et al. (2012) In Cell Metabolism 16(5). p.625-633
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... (More)
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. (Less)
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Contribution to journal
publication status
published
subject
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Cell Metabolism
volume
16
issue
5
pages
625 - 633
publisher
Cell Press
external identifiers
  • wos:000311765700011
  • pmid:23140642
  • scopus:84871426151
ISSN
1550-4131
DOI
10.1016/j.cmet.2012.10.009
language
English
LU publication?
yes
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fabcb2e5-647c-4e56-bc6c-8c0a021764fe (old id 3219063)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/23140642?dopt=Abstract
date added to LUP
2012-12-03 13:37:35
date last changed
2017-10-29 03:17:48
@article{fabcb2e5-647c-4e56-bc6c-8c0a021764fe,
  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.},
  author       = {Mahdi, Taman and Hänzelmann, Sonja and Salehi, S Albert and Jabar Muhammed, Sarheed and Reinbothe, Thomas and Tang, Yunzhao and Axelsson, Annika and Zhou, Yuedan and Jing, Xingjun and Almgren, Peter and Krus, Ulrika and Taneera, Jalal and Blom, Anna and Lyssenko, Valeriya and Esguerra, Jonathan and Hansson, Ola and Eliasson, Lena and Derry, Jonathan and Zhang, Enming and Wollheim, Claes and Groop, Leif and Renström, Erik and Rosengren, Anders},
  issn         = {1550-4131},
  language     = {eng},
  number       = {5},
  pages        = {625--633},
  publisher    = {Cell Press},
  series       = {Cell Metabolism},
  title        = {Secreted frizzled-related protein 4 reduces insulin secretion and is overexpressed in type 2 diabetes.},
  url          = {http://dx.doi.org/10.1016/j.cmet.2012.10.009},
  volume       = {16},
  year         = {2012},
}