Method of regulating glucose metabolism, and reagents related thereto
DCFirst Claim
1. A method for modifying metabolism of glucagon-like peptide 1 (GLP-1), 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 inhibit DPIV proteolysis of GLP-1 but not sufficient to suppress the immune system of the animal.
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Abstract
The present invention provides methods for modification and regulation of glucagon-like peptide 1 (GLP-1) metabolism by administering therapeutically effective amounts 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 inhibit DPIV proteolysis of GLP-1 but not sufficient to suppress the immune system of the animal.
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Citations
27 Claims
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1. A method for modifying metabolism of glucagon-like peptide 1 (GLP-1), 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 inhibit DPIV proteolysis of GLP-1 but not sufficient to suppress the immune system of the animal.
- the duration of the therapeutic effect is at least about 24 hours; and
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2. The method of claim 1, wherein the inhibitor has a Ki for inhibition of DPIV of 1.0 nM or less.
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3. The method of claim 2, wherein the inhibitor has a Ki for inhibition of DPIV of 0.1 nM or less.
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4. The method of claim 3, wherein the inhibitor has a Ki for inhibition of DPIV of 0.01 nM or less.
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5. The method of claim 1, wherein the inhibitor has an EC50 for modification of GLP-1 metabolism at least one order of magnitude less than its EC50 for immunosuppression.
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6. The method of claim 5, wherein the inhibitor has an EC50 for modification of GLP-1 metabolism at least two orders of magnitude less than its EC50 for immunosuppression.
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7. The method of claim 1, wherein the inhibitor has a molecular weight less than 5000 amu.
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8. The method of claim 7, wherein the inhibitor has a molecular weight less than 2000 amu.
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9. The method of claim 8, wherein the inhibitor has a molecular weight less than 1000 amu.
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10. The method of claim 1, wherein said inhibition of DPIV proteolysis of GLP-1 treats Type II diabetes.
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11. The method of claim 1, wherein the duration of the therapeutic effect is about 24 hours.
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12. The method of claim 1, wherein the animal is a human.
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13. The method of claim 1, wherein the inhibitor is administered in the form of a tablet.
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14. The method of claim 1, wherein the inhibitor is administered in the form of a coated tablet.
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15. The method of claim 1, wherein the animal is a human;
- and the duration of the therapeutic effect is about 24 hours.
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16. The method of claim 1, wherein the animal is a human;
- and the inhibitor has a molecular weight less than 1000 amu.
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17. The method of claim 1, wherein the animal is a human;
- and the inhibitor is administered in the form of a tablet.
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18. The method of claim 1, wherein the animal is a human;
- and the inhibitor is administered in the form of a coated tablet.
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19. The method of claim 1, wherein the inhibitor has a molecular weight less than 1000 amu;
- and the duration of the therapeutic effect is about 24 hours.
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20. The method of claim 1, wherein the inhibitor has a molecular weight less than 1000 amu;
- and the inhibitor is administered in the form of a tablet.
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21. The method of claim 1, wherein the inhibitor has a molecular weight less than 1000 amu;
- and the inhibitor is administered in the form of a coated tablet.
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22. The method of claim 1, wherein the duration of the therapeutic effect is about 24 hours;
- the animal is a human; and
the inhibitor is administered in the form of a tablet.
- the animal is a human; and
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23. The method of claim 1, wherein the duration of the therapeutic effect is about 24 hours;
- the animal is a human; and
the inhibitor is administered in the form of a coated tablet.
- the animal is a human; and
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24. The method of claim 1, wherein the duration of the therapeutic effect is about 24 hours;
- 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.
- the animal is a human;
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25. The method of claim 1, wherein the duration of the therapeutic effect is about 24 hours;
- 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.
- the animal is a human;
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26. The method of claim 1, wherein the duration of the therapeutic effect is about 24 hours;
- the animal is a human;
the inhibitor is administered in the form of a tablet;
the inhibitor has a molecular weight less than 1000 amu; and
said inhibition of DPIV proteolysis of GLP-1 treats Type II diabetes.
- the animal is a human;
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27. The method of claim 1, wherein the duration of the therapeutic effect is about 24 hours;
- the animal is a human;
the inhibitor is administered in the form of a coated tablet;
the inhibitor has a molecular weight less than 1000 amu; and
said inhibition of DPIV proteolysis of GLP-1 treats Type II diabetes.
- the animal is a human;
Specification