Claims
- 1. A method of treating an insulin-resistant disorder in mammals comprising administering to a mammal in need thereof an effective amount of Dickkopf-5 (Dkk-5).
- 2. The method of claim 1 wherein the disorder is non-insulin dependent diabetes mellitus (NIDDM) or obesity.
- 3. The method of claim 1 wherein the mammal is human and the administration is systemic.
- 4. The method of claim 1 wherein the Dkk-5 has at least about 85% amino acid sequence identity to SEQ ID NO:5 or has at least about 85% amino acid sequence identity to the sequence between residue 20 up to residue 30 and residue 347 of SEQ ID NO:5.
- 5. The method of claim 1 wherein the Dkk-5 comprises SEQ ID NO:5 or comprises the sequence between residue 20 up to residue 30 and residue 347 of SEQ ID NO:5.
- 6. The method of claim 5 wherein the Dkk-5 comprises the sequence between residues 25 and 347 of SEQ ID NO:5.
- 7. The method of claim 1 wherein the Dkk-5 is an internal cleavage protein fragment of SEQ ID NO:5 having N-terminal sequence MALFDWTDYEDLK (SEQ ID NO:8) and a molecular weight of about 16 kDa.
- 8. The method of claim 1 wherein the Dkk-5 is a mixture of an internal cleavage protein fragment of SEQ ID NO:5 having N-terminal sequence MALFDWTDYEDLK (SEQ ID NO:8) and a molecular weight of about 16 kDa and either a Dkk-5 comprising SEQ ID NO:5 or a Dkk-5 comprising the sequence between residue 20 up to residue 30 and residue 347 of SEQ ID NO:5.
- 9. The method of claim 1 further comprising administering an effective amount of an insulin-resistance-treating agent.
- 10. The method of claim 9 wherein the agent is insulin, IGF-1, or a sulfonylurea.
- 11. A method for detecting the presence or onset of an insulin-resistant disorder in a mammal comprising the steps of:
(a) measuring the amount of Dickkopf-5 (Dkk-5) in a sample from said mammal; and (b) comparing the amount determined in step (a) to an amount of Dkk-5 present in a standard sample, a decreased level in the amount of Dkk-5 in step (a) being indicative of the insulin-resistant disorder.
- 12. The method of claim 11 wherein the measuring is carried out using an anti-Dkk-5 antibody in an immunoassay.
- 13. The method of claim 12 wherein the anti-Dkk-5 antibody comprises a label.
- 14. The method of claim 13 wherein the label is selected from the group consisting of a fluorescent label, a radioactive label, or an enzyme label.
- 15. The method of claim 12 wherein the immunoassay is selected from the group consisting of a radioimmunoassay, an enzyme immunoassay, an enzyme-linked immunosorbent assay, a sandwich immunoassay, a precipitation assay, an immunoradioactive assay, a fluorescence immunoassay, a protein A immunoassay, and an immunoelectrophoresis assay.
- 16. The method of claim 18 wherein the insulin-resistant disorder is non-insulin dependent diabetes mellitus (NIDDM) or obesity.
- 17. The method of claim 11 wherein the Dkk-5 is a Dkk-5 comprising SEQ ID NO:5, or a Dkk-5 comprising the sequence between residue 20 up to residue 30 and residue 347 of SEQ ID NO:5, or an internal cleavage protein fragment of SEQ ID NO:5 having N-terminal sequence MALFDWTDYEDLK (SEQ ID NO:8) and a molecular weight of about 16 kDa, or a combination of said cleavage product and one or both of the Dkk-5 comprising SEQ ID NO:5 or comprising the sequence between residue 20 up to residue 30 and residue 347 of SEQ ID NO:5.
- 18. A diagnostic kit for detecting the presence or onset of an insulin-resistant disorder, said kit comprising:
(a) a container comprising an antibody that binds Dickkopf-5 (Dkk-5); (b) a container comprising a standard sample containing Dkk-5; and (c) instructions for using the antibody and standard sample to detect the disorder, wherein either the antibody that binds Dkk-5 is detectably labeled or the kit further comprises another container comprising a second antibody that is detectably labeled and binds to the Dkk-5 or to the antibody that binds Dkk-5.
- 19. The kit of claim 18 wherein the antibody that binds Dkk-5 is a monoclonal antibody.
- 20. The kit of claim 18 wherein the Dkk-5 is a Dkk-5 comprising SEQ ID NO:5, or a Dkk-5 comprising the sequence between residue 20 up to residue 30 and residue 347 of SEQ ID NO:5, or an internal cleavage protein fragment of SEQ ID NO:5 having N-terminal sequence MALFDWTDYEDLK (SEQ ID NO:8) and a molecular weight of about 16 kDa, or a combination of said cleavage product and one or both of the Dkk-5 comprising SEQ ID NO:5 or comprising the sequence between residue 20 up to residue 30 and residue 347 of SEQ ID NO:5.
- 21. A kit for treating an insulin-resistant disorder, said kit comprising:
(a) a container comprising Dkk-5; and (b) instructions for using the Dkk-5 to treat the disorder.
- 22. The kit of claim 21 wherein the disorder is non-insulin dependent diabetes mellitus (NIDDM) or obesity.
- 23. The kit of claim 21 wherein the container is a vial and the instructions specify placing the contents of the vial in a syringe for immediate injection.
- 24. The kit of claim 21 further comprising a container comprising an insulin-resistance-treating agent.
- 25. The kit of claim 21 wherein the Dkk-5 is a Dkk-5 comprising SEQ ID NO:5, or a Dkk-5 comprising the sequence between residue 20 up to residue 30 and residue 347 of SEQ ID NO:5, or an internal cleavage protein fragment of SEQ ID NO:5 having N-terminal sequence MALFDWTDYEDLK (SEQ ID NO:8) and a molecular weight of about 16 kDa, or a combination of said cleavage product and one or both of the Dkk-5 comprising SEQ ID NO:5 or comprising the sequence between residue 20 up to residue 30 and residue 347 of SEQ ID NO:5.
- 26. An isolated internal cleavage protein fragment of SEQ ID NO:5 having N-terminal sequence MALFDWTDYEDLK (SEQ ID NO:8) and a molecular weight of about 16 kDa.
- 27. A composition comprising the protein fragment of claim 26 and a carrier.
- 28. The composition of claim 27 further comprising a Dickkopf-5 (Dkk-5) comprising SEQ ID NO:5 or a Dkk-5 comprising the sequence between residue 20 up to residue 30 and residue 347 of SEQ ID NO:5.
- 29. The composition of claim 28 wherein the Dkk-5 comprises a sequence between residues 25 and 347 of SEQ ID NO:5.
- 30. A hybridoma producing a Dkk-5 antibody selected from the group consisting of PTA-3090, PTA-3091, PTA-3092, PTA-3093, PTA-3094, PTA-3095, and PTA-3096.
- 31. An antibody produced by any one of the hybridomas of claim 30.
RELATED APPLICATIONS
[0001] This application is a non-provisional application filed under 37 CFR 1.53(b)(1), claiming priority under 35 USC 119(e) to provisional application No. 60/329,947, filed Oct. 15, 2001, the contents of which are incorporated herein by reference.
Provisional Applications (1)
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Number |
Date |
Country |
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60329947 |
Oct 2001 |
US |