Methods of regulating glucose metabolism, and reagents related thereto
The present invention provides methods for modification and regulation of glucose metabolism by administering to an animal a therapeutically effective amount of an inhibitor of dipeptidylpeptidase IV (DPIV) or a pharmaceutically acceptable salt thereof, where the inhibitor has a Ki for inhibition of DPIV of 10 nM or less; and the inhibitor is administered in an amount sufficient to increase the plasma half-life of glucagon-like peptide 1 (GLP-1) but not sufficient to suppress the immune system of the animal.
1. A method for modifying glucose metabolism, comprising administering orally to an animal in need thereof a therapeutically effective amount of an inhibitor of dipeptidylpeptidase IV (DPIV) or a pharmaceutically acceptable salt thereof once daily, wherein the inhibitor has a Ki for inhibition of DPIV of 10 nM or less; the duration of the therapeutic effect is at least about 24 hours; and the inhibitor is administered in an amount sufficient to increase the plasma half-life of glucagon-like peptide 1 (GLP-1) but not sufficient to suppress the immune system of the animal.
2. The method of claim 1 , wherein the inhibitor has a Ki for inhibition of DPIV of 1.0 nM or less.
3. The method of claim 2 , wherein the inhibitor has a Ki for inhibition of DPIV of 0.1 nM or less.
4. The method of claim 3 , wherein the inhibitor has a Ki for inhibition of DPIV of 0.01 nM or less.
5. The method of claim 1 , wherein the inhibitor has an EC 50 for treatment of Type II diabetes at least one order of magnitude less than its EC 50 for immunosuppression.
6. The method of claim 5 , wherein the inhibitor has an EC 50 for treatment of Type II diabetes at least two orders of magnitude less than its EC 50 for immunosuppression.
7. The method of claim 1 , wherein the inhibitor has a molecular weight less than 5000 amu.
8. The method of claim 7 , wherein the inhibitor has a molecular weight less than 2000 amu.
9. The method of claim 8 , wherein the inhibitor has a molecular weight less than 1000 amu.
10. The method of claim 1 , wherein the animal is a mammal.
11. The method of claim 10 , wherein the mammal is a human.
12. The method of claim 1 , wherein the inhibitor is administered in a solid dosage form.
13. The method of claim 12 , wherein the solid dosage form is a tablet, capsule or pill.
14. The method of claim 12 , wherein the solid dosage form is a tablet.
15. The method of claim 14 , wherein the solid dosage form is a coated tablet.
16. The method of claim 1 , wherein the duration of the therapeutic effect is about 24 hours.
17. The method of claim 1 , wherein the animal is a human; and the duration of the therapeutic effect is about 24 hours.
18. The method of claim 1 , wherein the animal is a human; and the inhibitor has a molecular weight less than 1000 amu.
19. The method of claim 1 , wherein the animal is a human; and the inhibitor is administered in the form of a tablet, capsule or pill.
20. The method of claim 1 , wherein the animal is a human; and the inhibitor is administered in the form of a tablet.
21. The method of claim 1 , wherein the animal is a human; and the inhibitor is administered in the form of a coated tablet.
22. The method of claim 1 , wherein the animal is a human; the inhibitor is administered in the form of a tablet, capsule or pill; and the inhibitor has a molecular weight less than 1000 amu.
23. The method of claim 1 , wherein the animal is a human; the inhibitor is administered in the form of a tablet; and the inhibitor has a molecular weight less than 1000 amu.
24. The method of claim 1 , wherein the animal is a human; the inhibitor is administered in the form of a coated tablet; and the inhibitor has a molecular weight less than 1000 amu.
25. The method of claim 1 , wherein the animal is a human; the inhibitor is administered in the form of a tablet, capsule or pill; and the duration of the therapeutic effect is about 24 hours.
26. The method of claim 1 , wherein the animal is a human; the inhibitor is administered in the form of a tablet; and the duration of the therapeutic effect is about 24 hours.
27. The method of claim 1 , wherein the animal is a human; the inhibitor is administered in the form of a coated tablet; and the duration of the therapeutic effect is about 24 hours.
28. The method of claim 1 , wherein the animal is a human; the inhibitor is administered in the form of a tablet, capsule or pill; the duration of the therapeutic effect is about 24 hours; and the inhibitor has a molecular weight less than 1000 amu.
29. The method of claim 1 , wherein the animal is a human; the inhibitor is administered in the form of a tablet; the duration of the therapeutic effect is about 24 hours; and the inhibitor has a molecular weight less than 1000 amu.
30. The method of claim 1 , wherein the animal is a human; the inhibitor is administered in the form of a coated tablet; the duration of the therapeutic effect is about 24 hours; and the inhibitor has a molecular weight less than 1000 amu.