Use of pleitrophin for preventing and treating pancreatic diseases and/or obesity and/or metabolic syndrome

Abstract

The present invention discloses the protein pleitrophin secreted by the developing pancreas, and polynucleotides, which identify and encode this protein. The invention also relates to the use of these sequences in the diagnosis, study, prevention, and treatment of pancreatic diseases (e.g. diabetes), obesity, and/or metabolic syndrome.

1 .- 39 . (canceled) 
     
     
         40 . A method for lowering blood glucose level in a subject in need thereof, comprising administering to said subject a medicament comprising an acceptable carrier and a human pleiotrophin polypeptide or a functional fragment thereof. 
     
     
         41 . The method according to  claim 40 , wherein said human pleiotrophin polypeptide is
 (a) a polypeptide comprising the sequence set forth in SEQ ID NO: 2, or an isoform, fragment or variant of the polypeptide of SEQ ID NO: 2;   (b) a polypeptide encoded by the polynucleotide comprising the sequence set forth in SEQ ID NO: 1;   (c) a polypeptide which is encoded by a polynucleotide which, as a result of the genetic code, is degenerate with the polynucleotide sequence of (b);   (d) a polypeptide which is encoded by a polynucleotide which hybridizes at 50° C. in a solution containing 1×SSC and 0.1% SDS to the polynucleotide sequence of (b) or (c);   (e) a polypeptide which is at least 85% identical to the polypeptide of (a);   (f) a polypeptide that differs from the polypeptide of (a) to (e) by a mutation in the polynucleotide sequence encoding said polypeptide, wherein said mutation causes an alteration, deletion, duplication or premature stop in the encoded polypeptide.   
     
     
         42 . The method according to  claim 40 , comprising administering a human pleiotrophin polypeptide comprising the sequence set forth in SEQ ID NO: 2. 
     
     
         43 . The method according to  claim 40 , wherein said subject is suffering from diabetes. 
     
     
         44 . The method according to  claim 43 , wherein the diabetes is insulin dependent diabetes mellitus or non-insulin dependent diabetes mellitus. 
     
     
         45 . The method according to  claim 40 , wherein said human pleiotrophin polypeptide is
 (a) a polypeptide comprising the sequence set forth in SEQ ID NO: 2 or a functional fragment thereof;   (b) a polypeptide encoded by the polynucleotide comprising the sequence set forth in SEQ ID NO: 1;   (c) a polypeptide which is encoded by a polynucleotide which, as a result of the genetic code, is degenerate with the polynucleotide sequence of (b); or   (d) a polypeptide which is at least 95% identical to the polypeptide of (a).   
     
     
         46 . The method according to  claim 40 , wherein said human pleiotrophin polypeptide is a polypeptide comprising the sequence set forth in SEQ ID NO: 2 or a functional fragment comprising 6 to 50 contiguous amino acids of said SEQ ID NO: 2. 
     
     
         47 . A method for increasing insulin production by pancreatic β cells or generating functional pancreatic cells that express glucagon in a subject, comprising administering to said subject a medicament comprising an acceptable carrier and a human pleiotrophin polypeptide or a functional fragment thereof. 
     
     
         48 . The method according to  claim 47 , wherein said insulin production or said glucagon expression is increased in said subject in presence of glucose. 
     
     
         49 . The method according to  claim 47 , wherein said insulin production is increased by a factor of two in said subject in the presence of glucose when compared to the insulin production in said subject in the absence of glucose. 
     
     
         50 . The method according to  claim 47 , wherein said insulin production is increased by a factor of three in said subject in the presence of glucose when compared to the insulin production in said subject in the absence of glucose. 
     
     
         51 . A method for regulation of body weight in a subject in need thereof, comprising administering to said subject a medicament comprising an acceptable carrier and a human pleiotrophin polypeptide or a functional fragment thereof. 
     
     
         52 . A method according to  claim 52 , comprising regulating body weight in a subject suffering from obesity.