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

Autor: Yunzhao Tang, Ola Hansson, Thomas Reinbothe, Taman Mahdi, Yuedan Zhou, Jonathan M. J. Derry, Valeriya Lyssenko, Jalal Taneera, Leif Groop, Claes B. Wollheim, Xingjun Jing, Albert Salehi, Lena Eliasson, Ulrika Krus, Jonathan L.S. Esguerra, Peter Almgren, Anders Rosengren, Enming Zhang, Erik Renström, Sonja Hänzelmann, Sarheed Jabar Muhammed, Anna M. Blom, Annika S. Axelsson
Jazyk: angličtina
Rok vydání: 2012
Předmět:
endocrine system diseases
Calcium Channels/metabolism
Physiology
medicine.medical_treatment
Interleukin-1beta
Gene Expression
Type 2 diabetes
RNA
Small Interfering/metabolism
Mice
Gene expression
Insulin Secretion
Insulin
RNA
Small Interfering
Cells
Cultured
Islets of Langerhans/cytology/metabolism
geography.geographical_feature_category
Islet
Glucose/pharmacology
medicine.anatomical_structure
Insulin/metabolism/secretion
RNA Interference
SFRP4
Diabetes Mellitus
Type 2/metabolism/pathology
Signal transduction
medicine.symptom
Signal Transduction
medicine.medical_specialty
endocrine system
Calcium/metabolism
Inflammation
Biology
Exocytosis
Hemoglobin A
Glycosylated/metabolism
Islets of Langerhans
Wnt Proteins/metabolism
Internal medicine
Proto-Oncogene Proteins
medicine
Animals
Humans
ddc:612
Molecular Biology
Glycated Hemoglobin
Proto-Oncogene Proteins/antagonists & inhibitors/genetics/metabolism
geography
Pancreatic islets
Cell Biology
medicine.disease
Wnt Proteins
Endocrinology
Glucose
Diabetes Mellitus
Type 2
Interleukin-1beta/metabolism
Calcium
Calcium Channels
Cell and Molecular Biology
Zdroj: Cell Metabolism, Vol. 16, No 5 (2012) pp. 625-33
Cell Metabolism; 16(5), pp 625-633 (2012)
ISSN: 1550-4131
Popis: SummaryA 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.
Databáze: OpenAIRE
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