Treatment of diabetes, toll-like receptor 4 modulators and methods for using the same

Abstract

The present invention relates to treatment of diabetes, toll-like receptor 4 (TLR-4) modulators and methods for using the same. Particularly, the present invention provides an isolated peptide from pneumolysin (PLY peptide) which is effective in treatment of diabetes. In addition, the PLY peptide of the present invention is a TLR-4 antagonist and thus can be used in the treatment of a disease or condition associated with TLR-4 activation. The present invention also provides treatment of diabetes with a TLR-4 antagonist.

1 - 30 . (canceled) 
     
     
         31 . A method for inhibiting the activity of TLR-4 in a subject, comprising administering to a subject in need thereof an effective amount of a TLR-4 antagonist, wherein the TLR-4 antagonist blocks the binding of a MD2 protein to TLR-4. 
     
     
         32 . The method of  claim 31 , wherein the TLR-4 antagonist is a peptide targeting TLR-4, an anti-TLR-4 antibody, an interfering nucleic acid targeting TLR-4, or a small molecule that inhibits TLR-4. 
     
     
         33 . The method of  claim 31 , wherein the TLR-4 antagonist is selected from the group consisting of TLR4-IN-C34, NBP2-26244, and CLI-095. 
     
     
         34 . The method of  claim 31 , wherein the subject is a human patient having or suspected of having a disease or condition associated with TLR-4 activation. 
     
     
         35 . The method of  claim 34 , wherein the disease or condition associated with TLR-4 activation is an inflammatory disorder due to TLR4 activation. 
     
     
         36 . The method of  claim 35 , wherein the inflammatory disorder due to TLR4 activation is atherosclerosis. 
     
     
         37 . The method of  claim 35 , wherein the subject is diabetic. 
     
     
         38 . The method of  claim 37 , wherein the subject is a human patient having or suspected of having diabetes or a complication thereof. 
     
     
         39 . The method of  claim 31 , wherein the effective amount of the TLR-4 antagonist is sufficient to lower blood glucose levels or increase insulin levels of the subject. 
     
     
         40 . The method of  claim 38 , wherein the diabetes is type II diabetes.