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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/3219063
- author
- 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. (More)
- 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
; Almgren, Peter
LU
; Krus, Ulrika
LU
; Taneera, Jalal
LU
; Blom, Anna
LU
; Lyssenko, Valeriya
LU
; Esguerra, Jonathan
LU
; Hansson, Ola
LU
; Eliasson, Lena
LU
; Derry, Jonathan
; Zhang, Enming
LU
; Wollheim, Claes
LU
; Groop, Leif
LU
; Renström, Erik
LU
and Rosengren, Anders
LU
(Less)
- organization
-
- Diabetes - Islet Patophysiology (research group)
- Islet cell physiology (research group)
- Translational Muscle Research (research group)
- Protein Chemistry, Malmö (research group)
- Diabetes - Islet Cell Exocytosis (research group)
- EXODIAB: Excellence of Diabetes Research in Sweden
- EpiHealth: Epidemiology for Health
- publishing date
- 2012
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Cell Metabolism
- volume
- 16
- issue
- 5
- pages
- 625 - 633
- publisher
- Cell Press
- external identifiers
-
- wos:000311765700011
- pmid:23140642
- scopus:84871426151
- pmid:23140642
- ISSN
- 1550-4131
- DOI
- 10.1016/j.cmet.2012.10.009
- language
- English
- LU publication?
- yes
- id
- fabcb2e5-647c-4e56-bc6c-8c0a021764fe (old id 3219063)
- alternative location
- http://www.ncbi.nlm.nih.gov/pubmed/23140642?dopt=Abstract
- date added to LUP
- 2016-04-01 10:52:06
- date last changed
- 2024-01-07 02:58:35
@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 = {{https://lup.lub.lu.se/search/files/2198818/3878932.pdf}},
doi = {{10.1016/j.cmet.2012.10.009}},
volume = {{16}},
year = {{2012}},
}