Methods for treating diabetes

Abstract

Methods for treating diabetes by administering an inhibitor of GDF-8, or a related member of Transforming Growth Factor-beta (TGF-β) superfamily of structurally-related growth factors (e.g., GDF-11) are disclosed. Also disclosed are methods for upregulating expression of hexose transporters, such as GLUT4 and GLUT1, in a subject by administering an inhibitor of GDF-8. Also disclosed are methods for increasing glucose uptake by cells in a subject, by administering an inhibitor of GDF-8.

1 . A method of increasing expression of GLUT4 in a subject comprising administering to the subject a GDF-8 inhibitor, wherein the GDF-8 inhibitor is selected from the group consisting of a peptide fragment of GDF-8, a dominant-negative mutant of GDF-8, a GDF-8 receptor antagonist, an antisense nucleic acid which binds GDF-8 mRNA, an antibody or antibody fragment which binds to GDF-8 or its receptor, and an anti-GDF-8 ribozyme.  
   
   
       2 . A method of increasing insulin sensitivity and glucose uptake by cells in a subject comprising administering to the subject a GDF-8 inhibitor wherein the GDF-8 inhibitor is selected from the group consisting of a peptide fragment of GDF-8, a dominant-negative mutant of GDF-8, a GDF-8 receptor antagonist, an antisense nucleic acid which binds GDF-8 mRNA, an antibody or antibody fragment which binds to GDF-8 or its receptor, and an anti-GDF-8 ribozyme.  
   
   
       3 . A method of treating diabetes in a subject comprising administering to the subject a GDF-8 inhibitor wherein the GDF-8 inhibitor is selected from the group consisting of a peptide fragment of GDF-8, a dominant-negative mutant of GDF-8, a GDF-8 receptor antagonist, an antisense nucleic acid which binds GDF-8 mRNA, an antibody or antibody fragment which binds to GDF-8 or its receptor, and an anti-GDF-8 ribozyme.  
   
   
       4 . The method of any one of claims  1 - 3 , wherein the GDF-8 inhibitor is an antibody or antibody fragment.  
   
   
       5 . (canceled)  
   
   
       6 . The method of any one of claims  1 - 3 , wherein the peptide fragment of GDF-8 is derived from mature GDF-8 protein.  
   
   
       7 . The method of any one of claims  1 - 3 , wherein the peptide fragment of GDF-8 is derived from the pro domain of a GDF-8 protein.  
   
   
       8 . The method of  claim 2 , wherein said insulin sensitivity and glucose uptake is increased by modulating the expression of a hexose transporter selected from the group consisting of GLUT4 and GLUT1.  
   
   
       9 . The method of  claim 2 , wherein the cell is a muscle cell or a precursor thereof.  
   
   
       10 . The method of  claim 2 , wherein the cell is an adipocyte or a precursor thereof.  
   
   
       11 . The method of  claim 3 , wherein the subject is suffering from type II diabetes.  
   
   
       12 . The GDF-8 inhibitor of  claim 7 , wherein the inhibitor comprises amino acids 1-266 of the pro-domain.  
   
   
       13 . The GDF-8 inhibitor of  claim 1 , wherein the peptide fragment of GDF-8 spans the C-terminus of the mature GDF-8.