Methods of and compositions for stimulation of glucose uptake into muscle cells and treatment of diseases
First Claim
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1. A pharmaceutical composition comprising a concentration of betacellulin or an active variant or fragment thereof, wherein the concentration is sufficient to acutely reduce the blood glucose level in a subject without inducing hypoglycemia, and a pharmaceutically acceptable carrier.
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Abstract
The present invention relates to therapeutic uses of ErbB ligands, including betacellulin. The therapeutic uses include methods of using ErbB ligand family compounds alone, or in conjunction with other agents, for reducing blood glucose levels, treating Type I and Type II diabetes, obesity, muscle wasting diseases, and cardiotoxicity.
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Citations
58 Claims
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1. A pharmaceutical composition comprising a concentration of betacellulin or an active variant or fragment thereof, wherein the concentration is sufficient to acutely reduce the blood glucose level in a subject without inducing hypoglycemia, and a pharmaceutically acceptable carrier.
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2. A pharmaceutical composition comprising a concentration of long-acting betacellulin fusion protein comprising a betacellulin polypeptide or an active variant or fragment thereof and a fusion partner, wherein the betacellulin fusion protein has an extended half-life in a subject when compared to the betacellulin polypeptide alone, wherein the concentration is sufficient to perform an action selected from stimulating glucose or amino acid uptake into muscle cells, promoting cell survival or inhibiting apoptosis of muscle cells, inducing utrophin expression, inhibiting muscle wasting or increasing muscle mass, reducing HbA1c, reducing hypoglycemia associated with insulin administration, reducing the basal blood glucose level, and/or acutely reducing the elevated blood glucose level in the subject;
- and a pharmaceutically acceptable carrier.
- View Dependent Claims (3, 4, 5, 6, 7)
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8. A kit comprising:
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(a) a pharmaceutical composition comprising a polypeptide of the ErbB ligand family or an active variant or fragment thereof, either alone or as part of a long-acting fusion protein, wherein the fusion protein has an extended half-life in a subject when compared to the ErbB ligand polypeptide alone;
and a pharmaceutically acceptable carrier; and
(b) instructions for administration into a subject in need of such a composition. - View Dependent Claims (9, 10, 11, 12, 13, 14, 15, 16, 17, 18)
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19. A method of treating a disease in a subject comprising:
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(a) providing a polypeptide of the ErbB ligand family; and
(b) administering the polypeptide to the subject, wherein the subject has normal pancreatic function and/or a normal insulin level and wherein the subject would benefit from an action selected from stimulating glucose or amino acid uptake into muscle cells, reducing HbA1c, reducing hypoglycemia associated with insulin administration, reducing the basal blood glucose level, acutely reducing the elevated blood glucose level, promoting cell survival or inhibiting apoptosis of muscle cells, inducing utrophin expression, and inhibiting muscle wasting or increasing muscle mass. - View Dependent Claims (20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58)
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Specification