Methods and reagents for treating glucose metabolic disorders
First Claim
1. A method for inducing or enhancing the glucose-responsiveness of a pancreatic cell, which pancreatic cell has impaired cell function and which cell function is glucose-responsiveness, comprising administering to said pancreatic cell an amount of a PYY agonist or a biologically active fragment thereof, wherein said PYY agonist comprises the amino acid sequence having a sequence identical to the peptide encoded by the nucleic acid sequence wherein the nucleic acid sequence hybridizes under stringent conditions, including a wash step of 0.2×
- SSC at 65°
C., to SEQ ID NO;
1, wherein the amount of said PYY agonist or biologically active fragment thereof is sufficient to induce or enhance the glucose-responsiveness of said pancreatic cell, and wherein said PYY agonist or biologically active fragment thereof binds a PYY receptor and promotes glucose-responsiveness of said pancreatic cell.
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Accused Products
Abstract
The invention relates to methods for potentiating, enhancing or restoring glucose responsivity in pancreatic islets or cells. The methods can be used as therapies for diseases caused by, or coincident with, aberrant glucose metabolism, such as Type II Diabetes Mellitus.
60 Citations
65 Claims
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1. A method for inducing or enhancing the glucose-responsiveness of a pancreatic cell, which pancreatic cell has impaired cell function and which cell function is glucose-responsiveness, comprising administering to said pancreatic cell an amount of a PYY agonist or a biologically active fragment thereof, wherein said PYY agonist comprises the amino acid sequence having a sequence identical to the peptide encoded by the nucleic acid sequence wherein the nucleic acid sequence hybridizes under stringent conditions, including a wash step of 0.2×
- SSC at 65°
C., to SEQ ID NO;
1, wherein the amount of said PYY agonist or biologically active fragment thereof is sufficient to induce or enhance the glucose-responsiveness of said pancreatic cell, and wherein said PYY agonist or biologically active fragment thereof binds a PYY receptor and promotes glucose-responsiveness of said pancreatic cell. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 25, 26, 27, 30, 61, 62, 63, 64)
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10. A method for inducing or enhancing glucose metabolism in an animal having a disease associated with abnormal glucose metabolism, comprising administering to said animal a composition including an amount of a PYY agonist or a biologically active fragment thereof, wherein said PYY agonist comprises the amino acid sequence having a sequence identical to the peptide encoded by the nucleic acid sequence wherein the nucleic acid sequence hybridizes under stringent conditions, including a wash step of 0.2×
- SSC at 65°
C., to SEQ ID NO;
1, wherein the amount of said PYY agonist or biologically active fragment thereof is therapeutically effective to induce or enhance glucose metabolism in said animal, and wherein said PYY agonist or biologically active fragment thereof binds a PYY receptor and promotes glucose responsiveness. - View Dependent Claims (11, 12, 13, 14, 60)
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15. A method for treating a disease associated with altered glucose metabolism, comprising administering to an animal having a disease associated with altered glucose metabolism a composition comprising an amount of a PYY agonist or a biologically active fragment thereof, wherein said PYY agonist comprises the amino acid sequence having a sequence identical to the peptide encoded by the nucleic acid sequence wherein the nucleic acid sequence hybridizes under stringent conditions, including a wash step of 0.2×
- SSC at 65°
C., to SEQ ID NO;
1, wherein the amount of said PYY agonist or biologically active fragment thereof is sufficient to treat the disease, and wherein said PYY agonist or biologically active fragment binds a PYY receptor and promotes glucose responsiveness. - View Dependent Claims (16, 17, 18, 19, 20, 21, 22, 23, 24, 57, 58)
- SSC at 65°
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28. A method for maintaining or restoring a function of a pancreatic β
- cell, wherein the function is glucose responsivity or glucose sensing, comprising administering to a pancreatic cell, which pancreatic cell has impaired glucose responsivity or glucose sensing, a composition comprising an amount of a PYY agonist or a biologically active fragment thereof, wherein said PYY agonist comprises the amino acid sequence having a sequence identical to the peptide encoded by the nucleic acid sequence wherein the nucleic acid sequence hybridizes under stringent conditions, including a wash step of 0.2×
SSC at 65°
C., to SEQ ID NO;
1, wherein the amount of said PYY agonist or biologically active fragment thereof is sufficient to maintain or restore the function of said pancreatic β
cell, and wherein said PYY agonist or biologically active fragment binds a PYY receptor and promotes glucose-responsiveness of said pancreatic cell. - View Dependent Claims (29)
- cell, wherein the function is glucose responsivity or glucose sensing, comprising administering to a pancreatic cell, which pancreatic cell has impaired glucose responsivity or glucose sensing, a composition comprising an amount of a PYY agonist or a biologically active fragment thereof, wherein said PYY agonist comprises the amino acid sequence having a sequence identical to the peptide encoded by the nucleic acid sequence wherein the nucleic acid sequence hybridizes under stringent conditions, including a wash step of 0.2×
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31. A method for maintaining or restoring normal pancreatic function to a pancreatic cell having impaired pancreatic cell function, wherein the function is glucose responsivity or glucose sensing, comprising administering to a cultured pancreatic cell having altered pancreatic cell function an amount of a PYY agonist or a biologically active fragment thereof, wherein said PYY agonist comprises the amino acid sequence having a sequence identical to the peptide encoded by the nucleic acid sequence wherein the nucleic acid sequence hybridizes under stringent conditions, including a wash step of 0.2×
- SSC at 65°
C., to SEQ ID NO;
1, wherein the amount of said PYY agonist or biologically active fragment thereof is sufficient to maintain or restore normal pancreatic cell function to a pancreatic cell having altered pancreatic cell function, and wherein said PYY agonist or biologically active fragment binds a PYY receptor and promotes glucose-responsiveness of said pancreatic cell. - View Dependent Claims (32)
- SSC at 65°
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33. A method for inducing or enhancing the glucose-responsiveness of a pancreatic cell, which pancreatic cell has impaired glucose-responsiveness, comprising administering to said pancreatic cell an amount of a PYY comprising the amino acid sequence of SEQ ID NO:
- 2 or a biologically active fragment thereof, wherein the amount of said PYY or biologically active fragment thereof is sufficient to induce or enhance the glucose-responsiveness of said pancreatic cell, wherein the PYY or biologically active fragment thereof binds a PYY receptor and promotes glucose-responsiveness of said pancreatic cell.
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34. A method for inducing or enhancing glucose metabolism in an animal having a disease associated with abnormal glucose metabolism, comprising administering to said animal a composition including an amount of a PYY comprising the amino acid sequence of SEQ ID NO:
- 2 or a biologically active fragment thereof, wherein the amount of PYY or a biologically active fragment thereof is effective to induce or enhance glucose responsiveness in said animal, thereby inducing or enhancing glucose metabolism in said animal, and wherein the PYY or biologically active fragment thereof binds a PYY receptor and promotes glucose responsiveness.
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35. A method for treating a disease associated with altered glucose metabolism, comprising administering to an animal having a disease associated with altered glucose metabolism a composition comprising an amount of a PYY comprising the amino acid sequence of SEQ ID NO:
- 2 or a biologically active fragment thereof, wherein the amount of PYY or a biologically active fragment thereof is sufficient to treat the disease in said animal, and wherein the PYY or biologically active fragment thereof binds a PYY receptor and promotes glucose responsiveness.
- View Dependent Claims (36, 37, 38, 39, 56, 59)
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40. A method for maintaining or restoring a function of a pancreatic β
- cell, wherein the function is glucose responsivity or glucose sensing, comprising administering to a pancreatic cell, which pancreatic cell has impaired glucose responsivity or glucose sensing, a composition comprising an amount of a PYY comprising the amino acid sequence of SEQ ID NO;
2 or a biologically active fragment thereof, wherein the amount of said PYY or biologically active fragment thereof is sufficient to maintain or restore the function of said pancreatic β
cell, wherein the PYY or biologically active fragment thereof binds a PYY receptor and promotes glucose-responsiveness of said pancreatic cell.
- cell, wherein the function is glucose responsivity or glucose sensing, comprising administering to a pancreatic cell, which pancreatic cell has impaired glucose responsivity or glucose sensing, a composition comprising an amount of a PYY comprising the amino acid sequence of SEQ ID NO;
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41. A method for maintaining or restoring normal pancreatic cell function, wherein the function is glucose responsivity or glucose sensing, comprising administering to a cultured pancreatic cell, which pancreatic cell has impaired glucose responsivity or glucose sensing, an amount of a PYY comprising the amino acid sequence of SEQ ID NO:
- 2 or a biologically active fragment thereof, wherein the amount of said PYY or biologically active fragment thereof is sufficient to maintain or restore normal pancreatic cell function, wherein the PYY or biologically active fragment thereof binds a PYY receptor and promotes glucose-responsiveness of said pancreatic cell.
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42. A method for maintaining glucose-responsiveness of a pancreatic cell, comprising contacting the pancreatic cell, which pancreatic cell has impaired glucose responsivity or glucose sensing, with a composition comprising an amount of a PYY comprising the amino acid sequence of SEQ ID NO:
- 2 or a biologically active fragment thereof, wherein the amount of said PYY or biologically active fragment thereof is sufficient to maintain the glucose-responsiveness of the pancreatic cell, wherein the PYY or biologically active fragment thereof binds a PYY receptor and promotes glucose-responsiveness of said pancreatic cell.
- View Dependent Claims (47, 48)
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43. A method for maintaining glucose-responsiveness of a pancreatic cell, which pancreatic cell has impaired glucose-responsiveness, comprising contacting said pancreatic cell with a composition comprising an amount of a PYY agonist or a biologically active fragment thereof, wherein the amount of said PYY agonist or biologically active fragment thereof is sufficient to maintain the glucose responsiveness of said pancreatic cell, wherein said PYY agonist comprises the amino acid sequence having a sequence identical to the peptide encoded by the nucleic acid sequence wherein the nucleic acid sequence hybridizes under stringent conditions, including a wash step of 0.2×
- SSC at 65°
C., to SEQ ID NO;
1, and wherein said PYY agonist, or biologically active fragment binds a PYY receptor and promotes glucose-responsiveness of said pancreatic cell.
- SSC at 65°
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44. A method for inducing, enhancing, or maintaining glucose-responsiveness of a pancreatic cell, which pancreatic cell has impaired glucose-responsiveness, comprising contacting said pancreatic cell with a composition comprising an amount of a PYY agonist or a biologically active fragment thereof, wherein the amount of said PYY agonist or biologically active fragment thereof is sufficient to induce, enhance, or maintain the glucose-responsiveness of said pancreatic cell, wherein said PYY agonist comprises a polypeptide at least 80% identical with SEQ ID NO:
- 3, and wherein said PYY agonist, or biologically active fragment binds a PYY receptor and promotes glucose-responsiveness of said pancreatic cell.
- View Dependent Claims (45, 46)
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49. A method for treating a disease associated with altered glucose metabolism, comprising administering to an animal having a disease associated with altered glucose metabolism a composition comprising an amount of a PYY agonist or a biologically active fragment thereof effective to treat said disease associated with altered glucose metabolism, wherein said PYY agonist comprises a polypeptide at least 80% identical with SEQ ID NO:
- 3, and wherein said PYY agonist, or biologically active fragment binds a PYY receptor and promotes glucose responsiveness.
- View Dependent Claims (50, 51, 52, 53, 54, 55)
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65. A method for maintaining or restoring a function of a pancreatic islet, wherein the function is glucose responsivity or glucose sensing, comprising administering to a pancreatic islet, which pancreatic islet has impaired glucose responsivity or glucose sensing, a composition comprising an amount of a PYY agonist or a biologically active fragment thereof, wherein said PYY agonist comprises the amino acid sequence having a sequence identical to the peptide encoded by the nucleic acid sequence wherein the nucleic acid sequence hybridizes under stringent conditions, including a wash step of 0.2×
- SSC at 65°
C., to SEQ ID NO;
1, wherein the amount of said PYY agonist or biologically active fragment thereof is sufficient to maintain or restore the function of said pancreatic islet, and wherein said PYY agonist or biologically active fragment binds a PYY receptor and promotes glucose-responsiveness of said pancreatic islet.
- SSC at 65°
Specification