1. A method of detecting type 1 diabetes in a patient, comprising:
reacting a patient sample with a PBK1 protein or a fragment thereof under conditions that promote antibody-antigen binding; and
detecting the presence of an autoantibody in said sample.
2. The method of claim 1 wherein the PBK1 protein is immobilized on a solid support.
3. The method of claim 1 wherein the patient sample is selected from the group consisting of: blood, serum, plasma, and a biopsy tissue.
4. The method of claim 1 wherein the detecting of the autoantibody comprises reacting the autoantibody with an antibody having a detectable label.
5. A mammalian pancreas-derived cell comprising a recombinant nucleic acid encoding a PBK1 protein.
6. The mammalian pancreas-derived cell of claim 5 wherein the cell is a cell of a mammalian pancreas-derived cell line.
7. The pancreas-derived cell of claim 5 wherein the cell is a Min6 cell transfected with a recombinant nucleic acid encoding a PBK1 protein.
8. A method of identifying a PBK1 modulator, comprising one or more of:
a) contacting a PBK1 protein with a test agent under conditions that promote kinase activity of said PBK1 protein, and detecting an increase in the kinase activity; and
b) contacting a cell that expresses a PBK1 protein with a test agent under conditions that promote glucose-stimulated insulin secretion from said cell, and detecting an increase in the glucose-stimulated insulin secretion from the cell; wherein
said increase in a) or b) each indicates that the test agent is a PBK1 modulator.
9. The method of claim 8 further comprising determining that the increase in the glucose-stimulated insulin secretion comprises potentiation of secretagogue-stimulated insulin secretion from a cell that expresses a PBK1 protein.
10. The method of claim 8 wherein the cell is a mammalian pancreas-derived cell.
11. The method of claim 8 wherein the cell is a MIN6 cell.
12. The method of claim 8 wherein the cell contains a recombinant nucleic acid encoding a PBK1 protein.
13. A method of screening for an agent that treats a metabolic disease, said method comprising one or more of:
a) contacting a PBK1 protein with a test agent under conditions that promote binding of said test agent to said PBK1 protein, and detecting binding of said test agent to said PBK protein;
b) contacting a PBK1 protein with a test agent under conditions that promote kinase activity of said PBK1 protein, and detecting an increase in the kinase activity; and
c) contacting a cell that expresses a PBK protein with a test agent under conditions that promote glucose-stimulated insulin secretion from said cell, and detecting an increase in the glucose-stimulated insulin secretion from the cell; wherein
said disorder is selected from diabetes, type 2 diabetes, obesity, and diabetic retinopathy.
14. The method of claim 13, further comprising designating said test agent as a compound that treats said disease.
15. The method of claim 13, further comprising designating said test agent as a compound that treats said disease.
16. The method of claim 13, further comprising designating said test agent as a compound that treats type 2 diabetes.
17. The method of claim 13, wherein said PBK1 protein is selected from a protein having a polypeptide sequence that has at least 73%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the protein having a polypeptide sequence set forth in SEQ ID NO: 2.
18. The method of claim 17, wherein said PBK1 protein is selected from a protein having a polypeptide sequence set forth in SEQ ID NO: 2 or SEQ ID NO: 6
19. The method of claim 13 wherein a) is performed prior to c).
20. The method of claim 13 wherein b) is performed prior to c).
21. The method of claim 13 wherein a) is performed prior to b), and b) is performed prior to c).
22. The method of claim 13 further comprising determining that the increase in the glucose-stimulated insulin secretion comprises potentiation of secretagogue-stimulated insulin secretion from a cell that expresses a PBK1 protein.
23. The method of claim 13 wherein the cell is a mammalian pancreas-derived cell.
24. The method of claim 13 wherein the cell is a MIN6 cell.
25. The method of claim 13 wherein the cell contains a recombinant nucleic acid encoding a PBK1 protein.
26. A method for stimulating cell differentiation andor regeneration in a pancreatic beta cell comprising delivering PBK-1 DNA to said cell.
27. The method of claim 26 wherein said DNA is operably linked to a promoter that drives expression of said DNA in said cell.
28. A method for in vivo screening for an agent that treats diabetes, said method comprising:
a) subjecting a mammal comprising a PBK1 knockout genome to a diet that promotes diabetes;
b) treating said mammal with a test agent;
c) determining blood glucose level of said mammal; and
d) determining whether said mammal is glucose tolerant.
The claims below are in addition to those above.
All refrences to claim(s) which appear below refer to the numbering after this setence.
What is claimed is:
1. A fluid powered downhole vibration tool used in a well bore wherein fluids are pumped from the surface into a formation through said well bore, which comprises:
a downhole fluid powered motor in fluid communication with said fluids pumped from said surface; and
means to vibrate said well bore by action of said fluid powered motor.
2. A fluid powered downhole vibration tool as set forth in claim 1 wherein said means to vibrate includes a backward whirling mass.
3. A fluid powered downhole vibration tool as set forth in claim 1 wherein said means to vibrate includes a seismic mass rotated in said well bore.
4. A fluid powered downhole vibration tool used in a well bore wherein fluids are pumped from the surface into said well bore, which comprises:
a downhole turbine in fluid communication with said fluids pumped from said surface;
a fluid powered turbine motor in said well bore in communication with said turbine, wherein said turbine generates electricity; and
means to vibrate said well bore with said electricity produced by said motor.
5. A fluid powered downhole vibration tool as set forth in claim 3 wherein said means to vibrate is a seismic vibrator.
6. A method to power a downhole vibration tool in a well bore which method comprises:
pumping injection fluid from a surface into said well bore and into a formation;
pumping at least a portion of said injection fluid through a downhole turbine;
powering a downhole turbine motor with said turbine to produce electricity; and
vibrating said well bore with a vibrator powered by said generated electricity.