Methods for glucagon suppression
View Patent ↗Methods for use of an exendin, an exendin agonist, or a modified exendin or exendin agonist having an exendin or exendin agonist linked to one or more polyethylene glycol polymers, for example, for lowering glucagon levels and/or suppressing glucagon secretion in a subject are provide. These methods are useful in treating hyperglucagonemia and other conditions that would be benefited by lowering plasma glucagon or suppressing glucagon secretion.
1. A method of lowering plasma glucagon in a subject in need thereof, comprising:
identifying a subject in need of therapeutic lowering of plasma glucagon levels; and
administering to said subject a composition comprising a therapeutically effective glucagon lowering amount of an exendin, an exendin analog or combinations thereof;
wherein said exendin and exendin analog each have amino acid sequence that is more than 30 amino acid residues in length.
2. The method of claim 1 , wherein said subject is suffering from nocrolytic migratory erythema.
3. The method of claim 1 , wherein said subject has a glucagonoma.
4. The method of claim 1 , wherein the subject has a diabetes-related disorder.
5. The method of claim 4 , wherein the subject has type 2 diabetes.
6. The method of any of claims 1 - 5 , wherein said subject is a human.
7. The method of claim 1 , wherein said composition is provided in a dosage unit form and further comprises another anti-glucagon agent.
8. The method of claim 1 , wherein said composition comprises an exendin analog having an amino acid sequence selected from the sequences of SEQ ID NO: 47 and SEQ ID NO: 48.
9. The method of claim 8 , wherein said amino acid sequence has a sequence of SEQ ID NO: 47, wherein the Xaa in position 1 is His; the Xaa in position 2 is Gly, the Xaa in position 6 is Phe or naphthylalanine; the Xaa in position 14 is Leu, pentylglycine or Met; the Xaa in position 22 is Phe or naphthylalanine; the Xaa in position 23 is Ile or Val; the Xaa in position 25 is Phe, Tyr, or naphthylalanine; the Xaa in positions 31, 36, 37, and 38 are independently selected from Pro, homoproline, thioproline, and N-alkylalanine; and the Xaa in position 39 is Ser or Tyr.
10. The method of claim 8 , wherein said amino acid sequence has a sequence of SEQ ID NO: 47, wherein the Xaa in position 14 is Leu or pentylglycine; and the Xaa in position 22 is Phe or naphthylalanine.
11. The method of claim 8 , wherein said amino acid sequence has a sequence of SEQ ID NO: 48, wherein the Xaa in positions 6 and 22 are independently selected from Phe and naphthylalanine; the Xaa in position 23 is Ile or Val; and the Xaa in positions 30, 36, 37, and 38 are independently selected from Pro, homoproline, thioproline, and N-alkylalanine.
12. The method of claim 1 , wherein said composition comprises exendin-4.
13. A method of lowering plasma glucagon in a subject, comprising:
identifying a subject in need of therapeutic lowering of plasma glucagon levels; and
administering to said subject a composition consisting essentially of a therapeutically glucagon lowering amount of an exendin, an exendin analog or combinations thereof;
wherein said exendin and exendin analog each have an amino acid sequence that is more than 30 amino acid residues in length.
14. The method of claim 13 , wherein said subject is suffering from necrolytic migratory erythema.
15. The method of claim 13 , wherein said subject has a glucaganoma.
16. The method of claim 13 , wherein said composition consists essentially of exendin-4.
17. The method of claim 7 , wherein said anti-glucagon agent comprises amylin.
18. The method of claim 13 , wherein the subject has a diabetes-related disorder.
19. The method of claim 18 , wherein the subject has type 2 diabetes.
20. The method of any of claims 13 - 19 , wherein said subject is a human.
21. The method of claim 13 , wherein said composition consists essentially of an exendin analog having an amino acid sequence selected from the sequences of SEQ ID NO: 47 and SEQ ID NO: 48.
22. The method of claim 21 , wherein said amino acid sequence has a sequence of SEQ ID NO: 47, wherein the Xaa in position 1 is His; the Xaa in position 2 is Gly; the Xaa in position 6 is Phe or naphthylalanine; the Xaa in position 14 is Leu, pentylglycine or Met; the Xaa in position 22 is Phe or naphthylalanine; the Xaa in position 23 is Ile or Val; the Xaa in position 25 is Phe, Tyr, or naphthylalanine; the Xaa in positions 31, 36, 37, and 38 are independently selected from Pro, homoproline, thioproline, and N-alkylalanine; and the Xaa in position 39 is Ser or Tyr.
23. The method of claim 21 , wherein said amino acid sequence has a sequence of SEQ ID NO: 47, wherein the Xaa in position 14 is Leu pentylglycine, and the Xaa in position 22 is Phe or naphthylalanine.
24. The method of claim 21 , wherein said amino acid sequence has a sequence of SEQ ID NO: 48, wherein the Xaa in positions 6 and 22 are independently selected from Phe and naphthylalanine; the Xaa in position 23 is Ile or Val; and the Xaa in positions 30, 36, 37, and 38 are independently selected from Pro, homoproline, thioproline, and N-alkylalanine.