| First Author | Ezzat S | Year | 2013 |
| Journal | Cell Metab | Volume | 17 |
| Issue | 6 | Pages | 929-40 |
| PubMed ID | 23747250 | Mgi Jnum | J:199244 |
| Mgi Id | MGI:5501366 | Doi | 10.1016/j.cmet.2013.05.002 |
| Citation | Ezzat S, et al. (2013) The cancer-associated FGFR4-G388R polymorphism enhances pancreatic insulin secretion and modifies the risk of diabetes. Cell Metab 17(6):929-40 |
| abstractText | 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. |
