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.

What is claimed is:  
     
         1 . A method for treating diabetes mellitus in an individual in need thereof, said method comprising: 
 administering to said individual a composition providing at least one receptor ligand selected from the group consisting of a gastrin/CCK receptor ligand and an EGF receptor ligand in an amount sufficient to effect differentiation of pancreatic islet precursor cells to mature insulin-secreting cells.    
     
     
         2 . The method according to  claim 1 , wherein said at least one receptor ligand is an EGF receptor ligand selected from the group consisting of EGF1-53, EGF1-48, or its EGF1-47 or EGF1-49 congener.  
     
     
         3 . The method according to  claim 2 , wherein said EGF1-53, EGF1-48, or its EGF1-47 or EGF1-49 congener is human EGF1-53, EGF1-48, or its EGF1-47 or EGF1-49 or its congener.  
     
     
         4 . A method for providing a patient with diabetes in need thereof with a population of mature insulin-secreting beta cells, said method comprising: 
 transplanting into said patient cultured pancreatic islets which have been provided with a sufficient amount of at least one receptor ligand selected from the group consisting of a gastrin/CCK receptor ligand and an epidermal growth factor receptor ligand to induce proliferation of mature insulin-secreting beta cells of said islets prior to said transplanting.    
     
     
         5 . The method according to  claim 4 , wherein said diabetes is Type 2 diabetes.  
     
     
         6 . The method according to  claim 4 , wherein said gastrin/CCK receptor ligand is a gastrin.  
     
     
         7 . The method according to  claim 4 , wherein said epidermal growth receptor ligand is TGF-α or an EGF selected from the group consisting of EGF1-53, EGF1-48, or its EGF1-47 or EGF1-49 congener.  
     
     
         8 . A method for expanding a population of pancreatic beta cells, said method comprising: 
 providing said pancreatic beta cells with a sufficient amount of a gastrin/CCK receptor ligand and an epidermal growth factor receptor ligand to induce proliferation of said pancreatic beta cells, whereby an expanded population of pancreatic beta cells is obtained.    
     
     
         9 . A composition comprising: 
 pancreatic β cells, wherein said culture is obtained by providing pancreatic islets with a sufficient amount of a gastrin receptor agonist and an epidermal growth factor receptor agonist to induce proliferation of said pancreatic β cells.    
     
     
         10 . A method for treating diabetes in an individual in need thereof, said method comprising: 
 administering to said individual a composition comprising at least one receptor ligand selected from the group consisting of a proteinaceous gastrin/CCK receptor ligand and a proteinaceous EGF receptor ligand in an amount sufficient to effect differentiation of pancreatic islet precursor cells to mature insulin-secreting cells, wherein said composition is administered systemically.    
     
     
         11 . The method according to  claim 10 , wherein said proteinaceous gastrin/CCK receptor ligand is a gastrin.  
     
     
         12  The method according to  claim 10 , wherein said proteinaceous EGF receptor ligand is a TGF-α.  
     
     
         13 . The method according to  claim 10 , wherein said diabetes is type 2 diabetes.  
     
     
         14 . A method for stimulating pancreatic islet cell neogenesis in an individual in need thereof, said method comprising: 
 administering to said individual a composition comprising at least one receptor ligand selected from the group consisting of a gastrin/CCK receptor ligand and an EGF receptor ligand in an amount sufficient to effect differentiation of pancreatic islet precursor cells to mature insulin-secreting islet cells, wherein said composition is administered systemically.    
     
     
         15 . The method according to  claim 14 , wherein said individual.  
     
     
         16 . The method according to  claim 14 , wherein both said gastrin/CCK receptor ligand and said EGF receptor ligand are administered.  
     
     
         17 . The method according to  claim 16 , wherein at least one of said gastrin/CCK receptor ligand and said EGF receptor ligand is a proteinaceous receptor ligand.  
     
     
         18 . A method for treating diabetes mellitus in an individual in need thereof which comprises administering to the individual a composition providing a gastrin/CCK receptor ligand and an EGF receptor ligand in an amount sufficient to effect differentiation of pancreatic islet precursor cells to mature insulin-secreting cells.