GLP/1/exendin 4 IgG Fc fusion constructs for treatment of diabetes
The invention is a method and composition for the prevention and treatment of type I and type II diabetes in a subject. The composition comprises an IgG-Fc fusion protein where the fusion protein comprises GLP-1, mutant GLP-1, or exendin-4.
1. A pharmaceutical composition comprising a heterologous fusion protein comprising: a GLP-1 polypeptide selected from GLP-1 (7-37), GLP-1 (7-36) amide, and DPPIV resistant GLP-1, fused to a human IgG2 heavy chain constant region (Fc), and a leading sequence, wherein the leading sequence directs secretion of the synthesized fusion protein and wherein said human IgG2 Fc comprises SEQ ID NO:9.
2. The pharmaceutical composition of claim 1 , wherein cleavage of the leading sequence generates a fusion protein with a histidine residue at the N-terminus of the fusion protein.
3. The pharmaceutical composition of claim 1 , wherein the leading sequence comprises an IgK secretion leader peptide sequence, comprising SEQ ID NO:4; or a GHRH secretion leader peptide sequence, encoded by SEQ ID NO:10.
4. A pharmaceutical composition comprising a heterologous fusion protein comprising a GLP-1 polypeptide selected from GLP-1 (7-37), GLP-1 (7-36) amide, and DPPIV resistant GLP-1, fused to a human IgG2 heavy chain constant region (Fc), wherein said human IgG2 Fc comprises SEQ ID NO:9.
5. The pharmaceutical composition of claim 4 , wherein said DPPIV resistant GLP-1 is GLP-1A8G.
6. The pharmaceutical composition of claim 4 , wherein said fragment of GLP-1 comprises at least 29 amino acids and is GLP-1(7-37) or GLP-1(7-36) amide.