Methods for treating metabolic disorders using FGF
The method provides methods and compositions for treating metabolic disorders such as impaired glucose tolerance, elevated blood glucose, insulin resistance, dyslipidaemia, obesity, and fatty liver.
1. A method for treating an individual having type II diabetes, comprising systemically administering an FGF-1 compound having at least 80% identity to human FGF-1 to the individual in an amount effective to reduce blood glucose levels.
2. The method of claim 1 , wherein the FGF-1 compound is administered intravenously.
3. The method of claim 1 , wherein the FGF-1 compound is administered subcutaneously.
4. The method of claim 1 , wherein the FGF-1 compound is administered in combination with an additional therapeutic compound.
5. The method of claim 4 , wherein the additional therapeutic compound is an alpha-glucosidase inhibitor, amylin agonist, dipeptidyl-peptidase 4 (DPP-4) inhibitor, meglitinide, sulfonylurea, or a peroxisome proliferator-activated receptor (PPAR)-gamma agonist.
6. The method of claim 5 , wherein the PPAR agonist is a thiazolidinedione (TZD), aleglitazar, farglitazar, muraglitazar, or tesaglitazar.
7. The method of claim 6 , wherein the TZD is pioglitazone, rosiglitazone, rivoglitazone, or troglitazone.
8. The method of claim 1 , wherein the FGF-1 compound is a functional fragment of FGF-1 comprising at least 80% of human FGF-1.
9. The method of claim 8 , wherein the functional fragment of FGF-1 comprising at least 80% of human FGF-1 comprises at least 80% sequence identity to amino acids 1-140, amino acids 1-141, amino acids 14-135, or amino acids 13-135 of FGF-1.
10. The method of claim 8 , wherein the functional fragment of FGF-1 comprising at least 80% of human FGF-1 comprises amino acids 1-140, amino acids 1-141, amino acids 14-135, or amino acids 13-135 of FGF-1.
11. The method of claim 8 , wherein the functional fragment of FGF-1 comprising at least 80% of human FGF-1 consists of amino acids 1-140, amino acids 1-141, amino acids 14-135, or amino acids 13-135 of FGF-1.
12. The method of claim 8 , wherein the functional fragment of FGF-1 comprising at least 80% of human FGF-1 comprises at least 80% sequence identity to amino acids 14-135 of FGF1.
13. The method of claim 8 , wherein the functional fragment of FGF-1 comprising at least 80% of human FGF-1 comprises amino acids 14-135 of FGF-1.
14. The method of claim 8 , wherein the functional fragment of FGF-1 comprising at least 80% of human FGF-1 consists of amino acids 14-135 of FGF-1.
15. The method of claim 8 , wherein the functional fragment of FGF-1 comprising at least 80% of human FGF-1 comprises at least 90% sequence identity to amino acids 1-141 of FGF-1.
16. The method of claim 8 , wherein the functional fragment of FGF-1 comprising at least 80% of human FGF-1 comprises at least 95% sequence identity to amino acids 1-141 of FGF-1.
17. The method of claim 8 , wherein the functional fragment of FGF-1 comprising at least 80% of human FGF-1 comprises at least 98% sequence identity to amino acids 1-141 of FGF-1.
18. The method of claim 1 , wherein the FGF-1 compound is at least 90% identical to mature human FGF-1.
19. The method of claim 1 , wherein the FGF-1 compound is administered daily, twice daily, every other day, bi-weekly, weekly, or monthly.
20. The method of claim 1 , wherein the FGF-1 compound is a functional fragment of FGF-1 consisting of at least 90% of mature human FGF-1.
21. A method for treating an individual who is insulin resistant, comprising systemically administering an FGF-1 compound having at least 80% identity to human FGF-1 to the individual in an amount effective to reduce blood glucose levels.
22. The method of claim 21 , wherein the FGF-1 compound is administered intravenously.
23. The method of claim 22 , wherein the FGF-1 compound is administered subcutaneously.
24. The method of claim 21 , wherein the FGF-1 compound is administered in combination with an additional therapeutic compound.
25. The method of claim 24 , wherein the additional therapeutic compound is an alpha-glucosidase inhibitor, amylin agonist, dipeptidyl-peptidase 4 (DPP-4) inhibitor, meglitinide, sulfonylurea, or a peroxisome proliferator-activated receptor (PPAR)-gamma agonist.
26. The method of claim 25 , wherein the PPAR agonist is a thiazolidinedione (TZD), aleglitazar, farglitazar, muraglitazar, or tesaglitazar.
27. The method of claim 26 , wherein the TZD is pioglitazone, rosiglitazone, rivoglitazone, or troglitazone.
28. The method of claim 21 , wherein the FGF-1 compound is a functional fragment of FGF-1 comprising at least 80% of human FGF-1.
29. The method of claim 28 , wherein the functional fragment of FGF-1 comprising at least 80% of human FGF-1 comprises at least 80% sequence identity to amino acids 1-140, amino acids 1-141, amino acids 14-135, or amino acids 13-135 of FGF1.
30. The method of claim 28 , wherein the functional fragment of FGF-1 comprising at least 80% of human FGF-1 comprises amino acids 1-140, amino acids 1-141, amino acids 14-135, or amino acids 13-135 of FGF-1.
31. The method of claim 28 , wherein the functional fragment of FGF-1 comprising at least 80% of human FGF-1 consists of amino acids 1-140, amino acids 1-141, amino acids 14-135, or amino acids 13-135 of FGF-1.
32. The method of claim 28 , wherein the functional fragment of FGF-1 comprising at least 80% of human FGF-1 comprises at least 80% sequence identity to amino acids 14-135 of FGF-1.
33. The method of claim 28 , wherein the functional fragment of FGF-1 comprising at least 80% of human FGF-1 comprises amino acids 14-135 of FGF-1.
34. The method of claim 28 , wherein the functional fragment of FGF-1 comprising at least 80% of human FGF-1 consists of amino acids 14-135 of FGF-1.
35. The method of claim 21 , wherein the FGF-1 compound is at least 90% identical to mature human FGF-1.
36. The method of claim 28 , wherein the functional fragment of FGF-1 comprising at least 80% of human FGF-1 comprises at least 90% sequence identity to amino acids 1-141 of FGF-1.
37. The method of claim 28 , wherein the functional fragment of FGF-1 comprising at least 80% of human FGF-1 comprises at least 95% sequence identity to amino acids 1-141 of FGF-1.
38. The method of claim 28 , wherein the functional fragment of FGF-1 comprising at least 80% of human FGF-1 comprises at least 98% sequence identity to amino acids 1-141 of FGF-1.
39. The method of claim 1 , wherein the FGF-1 compound is administered daily, twice daily, every other day, bi-weekly, weekly, or monthly.
40. The method of claim 1 , wherein the FGF-1 compound is a functional fragment of FGF-1 consisting of at least 90% of mature human FGF-1.