Treatment for diabetes

Abstract

Methods and compositions for treating diabetes mellitus in a patient in need thereof are provided. The methods include administering to a patient a composition providing a gastrin/CCK receptor ligand, e.g., a gastrin, and/or an epidermal growth factor (EGF) receptor ligand, e.g., TGF-α, in an amount sufficient to effect differentiation of pancreatic islet precursor cells to mature insulin-secreting cells. The composition can be administered systemically or expressed in situ by cells transgenically supplemented with one or both of a gastrin/CCK receptor ligand gene, e.g., a preprogastrin peptide precursor gene and an EGF receptor ligand gene, e.g., a TGF-α gene. The methods also include transplanting into a patient cultured pancreatic islets in which mature insulin-secreting beta cells are proliferated by exposure to a gastrin/CCK receptor ligand and an EGF receptor ligand.

1 - 18  (canceled)  
     
     
         19 . A method for treating diabetes mellitus in an individual in need thereof, said method comprising: 
 administering to said individual a composition providing a gastrin/CCK receptor ligand that stimulates islet cell neogenesis in an amount sufficient to effect differentiation of pancreatic islet precursor cells to mature insulin-secreting cells.    
     
     
         20 . The method according to  claim 19 , wherein said ligand is a gastrin.  
     
     
         21 . The method according to  claim 20 , wherein said gastrin is selected from the group consisting of gastrin 34, gastrin 17, and gastrin 8.  
     
     
         22 . The method according to  claim 19 , wherein said ligand is a cholecystokinin.  
     
     
         23 . The method according to  claim 22 , wherein said cholecystokinin is selected from the group consisting of CCK 58, CCK 33, CCK 22, CCK 12 and CCK 8.  
     
     
         24 . The method according to  claim 19 , wherein said islet cell neogenesis is further stimulated when said ligand is administered in combination with an EGF receptor ligand.  
     
     
         25 . The method according to  claim 20 , wherein said ligand is an active analog of gastrin, an active fragment of gastrin or a modified gastrin.  
     
     
         26 . A method for treating diabetes in a patient in need thereof, said method comprising the step of: 
 ransplanting into said patient pancreatic islets which have been provided ex vivo with a sufficient amount of a gastrin/CCK receptor ligand to induce differentiation of precursor cells in said islets to mature insulin-secreting β-cells.    
     
     
         27 . The method according to  claim 26 , wherein the number of β-cells in said islets has been expanded prior to said transplanting step by providing said pancreatic islets with a sufficient amount of an EGF receptor ligand to increase the number of β-cells in said islets.  
     
     
         28 . The method according to  claim 19  or  claim 27 , wherein said diabetes is Type 2 diabetes.  
     
     
         29 . A method for enhancing production of mature insulin-secreting cells, said method comprising: 
 providing to a population of precursor cells an effective amount of a gastrin/CCK receptor ligand to effect differentiation of said precursor cells to mature insulin-secreting cells.    
     
     
         30 . A composition comprising: 
 pancreatic β cells, wherein said culture is obtained by providing precursor cells of said pancreatic β cells with a sufficient amount of a gastrin receptor agonist to induce differentiation of said precursor cells to mature pancreatic β cells.    
     
     
         31 . The method according to  claim 19 , wherein said composition is administered systemically.  
     
     
         32 . A method for stimulating pancreatic islet cell neogenesis in an individual in need thereof, said method comprising: 
 administering to said individual a composition comprising a gastrin in an amount sufficient to effect differentiation of pancreatic islet precursor cells to mature insulin-secreting islet cells, wherein said composition is administered systemically.    
     
     
         33 . The method according to  claim 19 , wherein said gastrin/CCK receptor ligand is a proteinaceous receptor ligand.  
     
     
         34 . A kit comprising: 
 one or more containers filled with one or more ingredient for a pharmaceutical composition comprising a gastrin receptor ligand.    
     
     
         35 . The kit according to  claim 34 , wherein said one or more ingredient are a gastrin and a pharmaceutical carrier.  
     
     
         36 . The kit according to  claim 34 , wherein said one or more ingredient are lyophilized.