Methods and compositions for treating diabetes

Abstract

The instant invention provides a method of treating an animal suffering a disease characterized by excessive apoptosis by administering a therapeutically effective amount of at least one serine protease inhibitor and thereafter monitoring a decrease in apoptosis. The inhibitor of the invention includes α 1 -antitrypsin or an α 1 -antitrypsin-like agent, including, but not limited to oxidation-resistant variants of α 1 -antitrypsin, and peptoids with antitrypsin activity. The diseases treatable by the invention include cancer, autoimmune disease, sepsis neurodegenerative disease, myocardial infarction, stroke, ischemia-reperfusion injury, toxin induced liver injury and AIDS. The method of the invention is also suitable for the prevention or amelioration of diseases characterized by excessive apoptosis.

What is claimed: 
     
         1 . A method for treating diabetes in a subject comprising administering to the subject a therapeutically effective amount of a composition comprising alpha-1-antitrypsin (AAT) or a derivative of the amino acid of AAT thereof, and treating diabetes in the subject. 
     
     
         2 . The method of  claim 1 , wherein the composition comprises AAT. 
     
     
         3 . The method of  claim 2 , wherein the AAT is substantially purified from a wild type, mutant, or transgenic mammalian source. 
     
     
         4 . The method of  claim 2 , wherein the AAT is isolated from a culture of wild type, mutant, or transformed cells. 
     
     
         5 . The method of  claim 1 , wherein the amount of AAT or the derivative thereof administered to the subject ranges from about 0.001 g/kg to about 7 g/kg of body weight of the subject. 
     
     
         6 . The method of  claim 1 , wherein the composition is administered parenterally, orally, nasally, buccally, intravenously, intramuscularly, subcutaneously, intrathecally, transdermally, by osmotic pump, by inhalation, or a combination thereof. 
     
     
         7 . The method of  claim 1 , wherein the subject is a human. 
     
     
         8 . The method of  claim 1 , wherein the composition is administered at least once daily. 
     
     
         9 . The method of  claim 1 , wherein the composition further comprises a pharmaceutically acceptable carrier. 
     
     
         10 . The method of  claim 1 , wherein the AAT or AAT derivative further comprises a oxydiazole, substituted thiazole, substituted triazole peptoid or a combination thereof. 
     
     
         11 . The method of  claim 1 , wherein the AAT or AAT derivative is a variant selected from Val 358 -antitrypsin, Ile 358 -antitrypsin, Leu 358 -antitrypsin, Phe 358 -antitrypsin, Tyr 358 -antitrypsin, or combinations thereof. 
     
     
         12 . A method for treating diabetes in a subject in need thereof, said method consisting of administering a therapeutically effective amount of alpha-1-antitrypsin (AAT) or a peptide derivative thereof, an aldehyde or ketone derivative thereof, or an oxidation-resistant or free-radical resistant derivative thereof, effective to inhibit apoptosis thereby treating diabetes in the subject. 
     
     
         13 . A method for treating diabetes by administering a composition parenterally, orally, buccally, intravenously, intramuscularly, subcutaneously, vaginally, rectally, epidurally, intrathecally, transdermally, intracerebroventricularly, by osmotic pump, or a combination thereof to a subject in need thereof, said composition consisting of a therapeutically effective amount of alpha-1 -antitrypsin (AAT) or a peptide derivative thereof, an aldehyde or ketone derivative thereof, or an oxidation-resistant or free-radical resistant derivative thereof, to treat diabetes in the subject. 
     
     
         14 . A method for treating diabetes by administering a composition parenterally, orally, buccally, intravenously, intramuscularly, subcutaneously, vaginally, rectally, epidurally, intrathecally, transdermally, intracerebroventricularly, by osmotic pump, or a combination thereof to a subject in need thereof, said composition consisting of a therapeutically effective amount of alpha-1 -antitrypsin (AAT) or a peptide derivative thereof, an aldehyde or ketone derivative thereof, or an oxidation-resistant or free-radical resistant derivative thereof, to inhibit apoptosis thereby treating diabetes in the subject. 
     
     
         15 . A method for treating diabetes, said method consisting of administering to a subject in need thereof by parenteral, oral, buccal, epidural, intravenous, intramuscular, subcutaneous, vaginal, rectal, intrathecal, transdermal, intracerebroventricular, osmotic pump administration or combination thereof, a therapeutically effective amount of alpha-1-antitrypsin (AAT) or a peptide derivative thereof, an aldehyde or ketone derivative thereof, or an oxidation-resistant or free-radical resistant derivative thereof, to treat diabetes in the subject. 
     
     
         16 . The method of any one of  claims 12  to  15 , wherein the amount of AAT or the derivative thereof administered to the subject ranges from about 0.01 g/kg to about 1 g/kg of body weight of the subject.