Inhibition of Jun Kinase

Abstract

A method of treating a metabolic disorder associated with insulin resistance by administering to a mammal an inhibitor of a NH2-terminal Jun Kinase (JNK), e.g., a compound or peptide which inhibits JNK1 expression or enzymatic activity.

1 . A method of treating a metabolic disorder associated with insulin resistance, comprising administering to a mammal an inhibitor of a NH2-terminal Jun Kinase (JNK).  
   
   
       2 . The method of  claim 1 , wherein said inhibitor binds to an ATP binding site in JNK.  
   
   
       3 . The method of  claim 1 , wherein said inhibitor binds to a catalytic domain of JNK.  
   
   
       4 . The method of  claim 1 , wherein said JNK is JNK1.  
   
   
       5 . The method of  claim 1 , wherein said JNK is JNK2.  
   
   
       6 . The method of  claim 1 , wherein said JNK is JNK1 and JNK2.  
   
   
       7 . The method of  claim 1 , wherein said inhibitor is SP600125.  
   
   
       8 . A method of improving insulin sensitivity, comprising administering to a mammal an inhibitor of a NH2-terminal Jun Kinase (JNK).  
   
   
       9 . A method of treating or preventing the development of obesity in an individual, comprising administering to said individual an inhibitor of a NH2-terminal Jun Kinase (JNK).  
   
   
       10 . A method of diagnosing insulin resistance or a risk of developing insulin resistance, comprising measuring the level of NH2-terminal Jun Kinase (JNK) activity in a tissue of a mammal, wherein an increase in activity compared to a normal control indicates that said mammal is suffering from or at risk of developing insulin resistance.  
   
   
       11 . A method of diagnosing insulin resistance or a risk of developing insulin resistance, comprising measuring the level of NH2-terminal Jun Kinase (JNK) expression in a tissue of a mammal, wherein an increase in the level of expression compared to a normal control indicates that said mammal is suffering from or at risk of developing insulin resistance.  
   
   
       12 . The method of  claim 10  or  11 , wherein said JNK is JNK1.  
   
   
       13 . A method of inhibiting fat accumulation in liver tissue, comprising contacting said tissue with an inhibitor of a JNK.  
   
   
       14 . The method of  claim 13 , wherein said inhibitor binds to an ATP binding site in JNK.  
   
   
       15 . The method of  claim 13 , wherein said inhibitor binds to a catalytic domain of JNK.  
   
   
       16 . The method of  claim 13 , wherein said JNK is JNK1.  
   
   
       17 . The method of  claim 13 , wherein said JNK is JNK2.  
   
   
       18 . The method of  claim 13 , wherein said JNK is JNK1 and JNK2.  
   
   
       19 . The method of  claim 13 , wherein said inhibitor is SP600125.  
   
   
       20 . The method of  claim 13 , wherein said inhibitor preferentially reduces enzymatic activity of JNK1 compared to JNK2.