Method of screening remedy for diabetes

Abstract

A convenient screening tool and a convenient screening method for obtaining an agent for treating diabetes, a pharmaceutical composition for treating diabetes, and a process for manufacturing the pharmaceutical composition are disclosed. The screening tool is a G protein-coupled receptor, a variation functionally equivalent thereto, or a homologous polypeptide thereof which promotes insulin secretion under a high glucose concentration by activation, or cells transformed with an expression vector comprising a polynucleotide encoding the above polypeptide and expressing the polypeptide.

1 . A screening tool for an agent for treating diabetes, wherein the tool is 
 (1) a polypeptide having an amino acid sequence of SEQ ID NO: 2 or 16, or    (2) a polypeptide having an amino acid sequence in which 1 to 10 amino acids are deleted, substituted, and/or added in an amino acid sequence of SEQ ID NO: 2 or 16, and exhibiting (a) an activity of promoting insulin secretion from pancreatic β cells by activation under a high glucose concentration and/or (b) an activity of increasing an amount of intracellular cAMP in the cells by activation.    
     
     
         2 . A screening tool for an agent for treating diabetes, wherein the tool is a polypeptide comprising an amino acid sequence of SEQ ID NO: 2 or 16, and exhibiting (a) an activity of promoting insulin secretion from pancreatic β cells by activation under a high glucose concentration and/or (b) an activity of increasing an amount of intracellular cAMP in the cells by activation.  
     
     
         3 . A screening tool for an agent for treating diabetes, wherein the tool is a polypeptide having an amino acid sequence having a 90% or more homology with an amino acid sequence of SEQ ID NO: 2 or 16, and exhibiting (a) an activity of promoting insulin secretion from pancreatic β cells by activation under a high glucose concentration and/or (b) an activity of increasing an amount of intracellular cAMP in the cells by activation.  
     
     
         4 . The screening tool for an agent for treating diabetes according to any one of  claims 1  to  3 , wherein the polypeptide exhibits (a) an activity of promoting insulin secretion from pancreatic β cells by activation under a high glucose concentration and (b) an activity of increasing an amount of intracellular cAMP in the cells by activation.  
     
     
         5 . A screening tool for an agent for treating diabetes, wherein the tool is a polypeptide consisting of an amino acid sequence of SEQ ID NO: 2 or 16.  
     
     
         6 . A screening tool for an agent for treating diabetes, wherein the tool is a cell which is transformed with an expression vector comprising a polynucleotide encoding a polypeptide according to any one of  claims 1  to  5  and is expressing the polypeptide.  
     
     
         7 . A method for screening an agent for treating diabetes, comprising the steps of: 
 bringing a cell according to  claim 6  or a cell membrane thereof into contact with a compound to be tested; and    analyzing whether or not a polypeptide according to any one of  claims 1  to  5  is activated.    
     
     
         8 . A method for screening an agent for treating diabetes, comprising the steps of: 
 bringing a cell according to  claim 6  or a cell membrane thereof, or a polypeptide according to any one of  claims 1  to  5  into contact with a compound to be tested, in the presence of a labeled agonist of a polypeptide according to any one of  claims 1  to  5 ; and    analyzing a change of an amount of the labeled agonist which binds to the cell, the cell membrane thereof, or the polypeptide.    
     
     
         9 . The screening method according to  claim 7  or  8 , wherein the agent for treating diabetes is an agent for promoting insulin secretion.  
     
     
         10 . A pharmaceutical composition for treating diabetes containing a substance activating a polypeptide according to any one of  claims 1  to  5 .  
     
     
         11 . A pharmaceutical composition for treating diabetes containing a substance is obtainable by a method according to  claim 7  or  8 .  
     
     
         12 . The pharmaceutical composition for treating diabetes according to  claim 10  or  11 , wherein it is a pharmaceutical composition for promoting insulin secretion.  
     
     
         13 . A process for manufacturing a pharmaceutical composition for treating diabetes, comprising the steps of: 
 bringing a cell according to  claim 6  or a cell membrane thereof into contact with a compound to be tested;    analyzing whether or not a polypeptide according to any one of  claims 1  to  5  is activated; and    preparing a formulation containing the analyzed substance.    
     
     
         14 . A process for manufacturing a pharmaceutical composition for treating diabetes, comprising the steps of: 
 bringing a cell according to  claim 6  or a cell membrane thereof into contact with a compound to be tested, in the presence of a labeled agonist of a polypeptide according to any one of  claims 1  to  5 ;    analyzing a change of an amount of the labeled agonist which binds to the cell or the cell membrane thereof; and    preparing a formulation containing the analyzed substance.    
     
     
         15 . The process for manufacturing according to  claim 13  or  14 , wherein the pharmaceutical composition for treating diabetes is a pharmaceutical composition for promoting insulin secretion.  
     
     
         16 . A method for treating diabetes, comprising administering to a subject in need thereof a substance activating a polypeptide according to any one of  claims 1  to  5  in an effective amount thereof.  
     
     
         17 . A method for promoting insulin secretion, comprising administering to a subject in need thereof a substance activating a polypeptide according to any one of  claims 1  to  5  in an effective amount thereof.  
     
     
         18 . Use of a substance activating a polypeptide according to any one of  claims 1  to  5 , in the manufacture of a pharmaceutical composition for treating diabetes and/or a pharmaceutical composition for promoting insulin secretion.