Urocortin-iii and uses thereof

Abstract

A search of the public human genome database identified a human EST, GenBank accession number AW293249, which has high homology to known pufferfish urocortin sequences. The full length sequence was amplified from human genomic DNA and sequenced. Sequence homology comparisons of the novel sequence with human urocortin I and urocortin II revealed that the sequence encoded a novel human urocortin, which was designated urocortin III (UcnIII). While urocortin III does not have high affinity for either CRF-R1 or CRF-R2, the affinity for CRF-R2 is greater than the affinity for CRF-R1. Urocortin III is capable stimulating cyclic AMP production in cells expressing CRF-R2α or β. Thus, the affinity is high enough that urocortin III could act as a native agonist of CRF-R2. However, it is also likely that urocortin III is a stronger agonist of a yet to b e identified receptor.

1 - 77 . (canceled) 
     
     
         78 . A method of treating diabetes or pre-diabetes in a subject comprising administering to the individual an effective amount of an isolated DNA sequence comprising a nucleotide sequence encoding the amino acid sequence of SEQ ID NO:3 or SEQ ID NO:5, positioned under the control of a heterologous promoter, thereby treating the diabetes or pre-diabetes in the subject. 
     
     
         79 . The method of  claim 78 , wherein the nucleotide sequence encodes the amino acid sequence of SEQ ID NO:3. 
     
     
         80 . The method of  claim 78 , wherein the nucleotide sequence encodes the amino acid sequence of SEQ ID NO:5. 
     
     
         81 . The method of  claim 78 , wherein the nucleotide sequence and promoter are positioned in a vector. 
     
     
         82 . The method of  claim 81 , wherein the vector is a virus, plasmid, phage or cosmid. 
     
     
         83 . The method of  claim 81 , wherein the vector is an expression vector. 
     
     
         84 . The method of  claim 78 , wherein the nucleotide sequence and promoter are comprised in an expression vector. 
     
     
         85 . The method of  claim 78 , wherein the subject is a human. 
     
     
         86 . The method of  claim 79 , wherein the DNA sequence is SEQ ID NO:1.