Specific antagonists for glucose-dependent insulinotropic polypeptide (GIP)

Abstract

In one embodiment, this invention provides an antagonist of glucose-dependent insulinotropic polypeptide (GIP) consisting essentially of a 24 amino acid polypeptide corresponding to positions 7-30 of the sequence of GIP. In another embodiment, this invention provides a method of preventing and treating obesity and non-insulin dependent diabetes mellitus (Type II) in a patient comprising administering to the patient an antagonist of glucose-dependent insulinotropic polypeptide (GIP). In yet another embodiment, this invention provides a method of improving glucose tolerance in a mammal comprising administering to the mammal an antagonist of glucose-dependent insulinotropic polypeptide (GIP).

1 ) An antagonist of glucose-dependent insulinotropic polypeptide (GIP) consisting essentially of a 24 amino acid polypeptide corresponding to positions 7-30 of the sequence of GIP.  
     
     
         2 ) A method of treating non-insulin dependent diabetes mellitus in a patient comprising administering to the patient an antagonist of glucose-dependent insulinotropic polypeptide (GIP).  
     
     
         3 ) A method of improving glucose tolerance in a non-insulin dependent diabetes mellitus patent comprising administering to the patient an antagonist of glucose-dependent insulinotropic polypeptide (GIP).  
     
     
         4 ) A method of preventing, inhibiting or reducing obesity in an animal comprising administering to the animal an antagonist of glucose-dependent insulinotropic polypeptide (GIP) to inhibit, block or reduce glucose absorption from the intestine of the animal.  
     
     
         5 ) A method according to  claim 4 , wherein the animal is a human.  
     
     
         6 ) A method according to  claim 4 , wherein the antagonist comprises at least an effective number of amino acids corresponding to those amino acids in positions 7-30 of the sequence of GIP or effective alternative sequences thereto.  
     
     
         7 ) A method according to  claim 5 , wherein the antagonist comprises a 24 amino acid polypeptide corresponding to positions 7-30 of the sequence of GIP or effective alternative sequences thereto.  
     
     
         8 ) An antagonist of glucose-dependent insulinotropic polypeptide (GIP).  
     
     
         9 ) An antagonist according to  claim 8 , wherein said antagonist comprises at least an effective number of amino acids corresponding to those amino acids in posts 7-30 of the sequence of GIP or effective alternative sequences thereto.  
     
     
         10 ) An antagonist according to  claim 8 , wherein said antagonist comprises a 24 amino acid polypeptide corresponding to positions 7-30 of the sequence of GIP or effective alternative sequences thereto.  
     
     
         11 ) A pharmaceutical composition for preventing, inhibiting or reducing obesity in an animal comprising: 
 an effective amount of an antagonist of glucose-dependent insulinotropic polypeptide (GIP) to inhibit, block or reduce glucose absorption from the intestine of the animal; and    an acceptable pharmaceutical carrier.    
     
     
         12 ) A pharmaceutical composition according to  claim 11 , wherein the antagonist comprises at least an effective number of amino acids corresponding to those amino acids in positions 7-30 of the sequence of GIP or effective alternatives thereto.  
     
     
         13 ) A pharmaceutical composition according to  claim 11 , wherein the antagonist comprises a 24 amino acid polypeptide corresponding to positions 7-30 of the sequence of GIP or effective alternatives thereto.  
     
     
         14 ) A pharmaceutical composition according to  claim 11 , said pharmaceutical composition further including an inert pharmaceutical excipient selected from the group consisting of sweetening, flavoring, coloring, dispersing, disintegrating, binding, granulating, suspending, wetting, preservative and demulcent agents.  
     
     
         15 ) An antagonist according to  claim 8 , wherein the antagonist is lyophilized.  
     
     
         16 ) An antagonist of  claim 15 , wherein the lyophilized antagonist is reconstituted with a suitable diluent selected from the group consisting of normal saline, sterile water, glacial acetic acid, sodium acetate and combinations thereof.  
     
     
         17 ) A method of developing a nonpeptide GIP antagonist comprising: 
 using a GIP antagonist to identify characteristics of the GIP antagonist or the antagonist properties of a GIP antagonist; and    developing a nonpeptide GIP antagonist which has characteristics similar to the GIP antagonist or antagonist properties of the GIP antagonist.    
     
     
         18 ) An antagonist according to  claim 8 , wherein said antagonist comprises an amino acid sequence at least 95% identical to SEQ ID NO:8.  
     
     
         19 ) An antagonist according to  claim 8 , wherein said polypeptide antagonist comprises SEQ ID NO:8.  
     
     
         20 ) A pharmaceutical composition according to  claim 11 , wherein the antagonist is a polypeptide comprising an amino acid sequence at least 95% identical to SEQ ID NO:8.  
     
     
         21 ) A phamaceuitical composition according to  claim 11 , wherein the antagonist comprising an amino acid sequence identical to SEQ ID NO:8.