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Ezzat, S.* ; Zheng, L.* ; Florez, J.C.* ; Stefan, N. ; Mayr, T.* ; Hliang, M.M.* ; Jablonski, K.A.* ; Harden, M.* ; Stancáková, A.* ; Laakso, M.* ; Häring, H.-U.* ; Ullrich, A.* ; Asa, S.L.*

The cancer-associated FGFR4-G388R polymorphism enhances pancreatic insulin secretion and modifies the risk of diabetes.

Cell Metab. 17, 929-940 (2013)
DOI PMC
Open Access Green as soon as Postprint is submitted to ZB.
The fibroblast growth factor receptor 4 (FGFR4)-R388 single-nucleotide polymorphism has been associated with cancer risk and prognosis. Here we show that the FGFR4-R388 allele yields a receptor variant that preferentially promotes STAT3/5 signaling. This STAT activation transcriptionally induces Grb14 in pancreatic endocrine cells to promote insulin secretion. Knockin mice with the FGFR4 variant allele develop pancreatic islets that secrete more insulin, a feature that is reversed through Grb14 deletion and enhanced with FGF19 administration. We also show in humans that the FGFR4-R388 allele enhances islet function and may protect against type 2 diabetes. These data support a common genetic link underlying cancer and hyperinsulinemia.
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Publication type Article: Journal article
Document type Scientific Article
ISSN (print) / ISBN 1550-4131
e-ISSN 1932-7420
Journal Cell Metabolism
Quellenangaben Volume: 17, Issue: 6, Pages: 929-940 Article Number: , Supplement: ,
Publisher Elsevier
Reviewing status Peer reviewed
Institute(s) Institute of Diabetes Research and Metabolic Diseases (IDM)