The FGFs are a family of more than 20 small (~17-26 kDa) secreted peptides. The initial characterization of these proteins focused on their ability to stimulate fibroblast proliferation. FGFs modulate cellular activity via at least 5 distinct subfamilies of high-affinity FGF receptors (FGFRs): FGFR-1, -2, -3, and -4, all with intrinsic tyrosine kinase activity and, except for FGFR-4, multiple splice isoforms, and FGFR-5, which lacks an intracellular kinase domain. There is growing evidence that FGFRs can be important for regulation of glucose and lipid homeostasis. FGFR-2 appears to be a key molecule during pancreatic development and FGFR-4 has been implicated in cholesterol metabolism and bile acid synthesis. FGF-21 is preferentially expre