The cancer-associated FGFR4-G388R polymorphism enhances pancreatic insulin secretion and modifies the risk of diabetes.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 23747250.
- Also identified by DOI 10.1016/j.cmet.2013.05.002 and PMC identifier 4005358.
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Abstract
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.
Medical subject headings
- Insulin
- Proteins
- Receptor, Fibroblast Growth Factor, Type 4
- STAT3 Transcription Factor
- STAT5 Transcription Factor