Method for the improvement of islet signaling in diabetes mellitus and for its prevention

Abstract

The present invention discloses a method for therapeutically treating mammals, including but not limited to humans, to increase the relative insulin producing performance of endogenous pancreatic β-cells and to cause differentiation of pancreatic epithelial cells into insulin producing β-cells. Oral administration a DP IV inhibitor causes the active form of GLP-1 to be preserved longer under physiological conditions. The extended presence of GLP-1, in particular in the pancreatic tissue facilitates differentiation and regeneration of the β-cells already present that are in need of repair. These repaired insulin producing cells can contribute to the correction and maintenance of normal physiological glycemic levels.

1 . A method for increasing the capacity of insulin providing cells in an animal comprising administering to said animal a therapeutically effective dose of at least one DP IV enzyme activity effector.  
     
     
         2 . The method of  claim 1  wherein said increasing the capacity of insulin producing cells comprises causing endogenous insulin producing cells to become more effective insulin producers.  
     
     
         3 . The method of  claim 1  wherein said increasing the capacity of insulin producing cells comprises causing cells present in the pancreas to differentiate into insulin producing cells.  
     
     
         4 . The method of  claim 1  wherein said DP IV effector is selected from the group consisting of N-(N′-substituted glycyl)-2-cyanopyrrolidines, N-aminoacyl thiazolidines, N-aminoacyl pyrrolidines: such as L-threo-isoleucyl thiazolidine (P32/98), L-allo-isoleucyl thiazolidine, L-threo-isoleucyl pyrrolidine, and L-allo-isoleucyl pyrrolidine and pharmaceutical salts thereof.  
     
     
         5 . The method of  claim 1  wherein said effector comprises a substrate capable of binding with said DP IV and which competes with naturally occurring substrates for DP IV.  
     
     
         6 . The method of  claim 1  wherein said administration comprises oral administration.  
     
     
         7 . The method of  claim 1  wherein said administration comprises iv or im injection.  
     
     
         8 . The method of  claim 1  wherein said administration comprises chronic oral administration.  
     
     
         9 . The method of  claim 1  wherein said administration comprises chronic iv or im injection.  
     
     
         10 . The method of  claim 1  further comprising the administration of glucose or the intake of food takes place before, during or after the administration of said DP IV activity effector.  
     
     
         11 . The method of  claim 8  wherein said administration of said DP IV activity effector occurs before said administration of glucose, or intake of food.