Chimeric fibroblast growth factor 21 proteins and methods of use

A method for decreasing blood glucose level in a subject suffering from diabetes, the method comprising:

• selecting a subject suffering from diabetes;
• providing a chimeric fibroblast growth factor (FGF) protein, wherein the chimeric FGF protein comprises an N-terminus coupled to a C-terminus, wherein the N-terminus comprises an FGF2 portion beginning at any one of residues 1 to 25 and ending at any one of residues 151 to 155 of SEQ ID NO:
• 121, wherein the FGF2 amino acid positions corresponding to those selected from the group consisting of N36, K128, R129, K134, K138, Q143, K144, and combinations thereof are substituted to decrease binding affinity for heparin and/or heparan sulfate compared to FGF2 without the substitution, and wherein the C-terminus comprises a portion of an FGF21 comprising amino acid residues 168 to 209 of SEQ ID NO:
• 233;
• and
• administering to said selected subject an effective amount of the chimeric FGF protein to decrease blood glucose level in the selected subject.