Peptides acting as both GLP-1 receptor agonists and glucagon receptor antagonists and their pharmacological methods of use
The invention provides polypeptides that act both as an agonist of the GLP-1 receptor and an antagonist of the glucagon receptor. Such polypeptides are useful for treating individuals with type 2 diabetes or other metabolic disorders.
1. An isolated polypeptide consisting of SEQ ID NO:8, wherein said polypeptide acts as both a GLP-1 receptor agonist and a glucagon receptor antagonist.
2. A pharmaceutical composition comprising a polypeptide of claim 1 in combination with a pharmaceutically acceptable carrier.
3. A method of treating a metabolic disorder associated with type 2 diabetes in a mammal, comprising administering to the mammal a therapeutically effective amount of the polypeptide of claim 1 , wherein said metabolic disorder is selected from the group consisting of: type 2 diabetes associated impaired glucose tolerance, impaired fasting glucose, and obesity.
4. The method of claim 3 , wherein said therapeutically effective amount ranges from about 0.1 μg/kg to about 1 mg/kg.
5. The polypeptide of claim 1 , wherein the polypeptide is a PEGylated form of SEQ ID NO:8.
6. The pharmaceutical composition of claim 2 , wherein said polypeptide is a PEGylated form of SEQ ID NO:8.
7. The method of claim 3 , wherein the polypeptide is a PEGylated form of SEQ ID NO:8.
8. The method of claim 7 , wherein said therapeutically effective amount ranges from about 0.1 μg/kg to about 1 mg/kg.
9. A method of treating a metabolic disorder associated with type 2 diabetes in a mammal, comprising administering to the mammal a therapeutically effective amount of a polypeptide of claim 6 , wherein said metabolic disorder is selected from the group consisting of: type 2 diabetes associated impaired glucose tolerance, impaired fasting glucose, and obesity.
10. A method of treating type 2 diabetes in a mammal comprising administering to the mammal a therapeutically effective amount of an isolated polypeptide consisting of SEQ ID NO:8, wherein said polypeptide acts as both a GLP-1 receptor agonist and a glucagon receptor antagonist.
11. The method of claim 10 , wherein said polypeptide further comprises a pharmaceutically acceptable carrier.