Compositions and methods of using proislet peptides and analogs thereof

Abstract

Embodiments relate to proislet peptides, preferably HIP, that exhibit increased stability and efficacy, and methods of using the same to treating a pathology associated with impaired pancreatic function, including type 1 and type 2 diabetes and symptoms thereof.

1 - 12 . (canceled) 
     
     
         13 . A modified proislet peptide comprising a C-terminal amide group and an N-terminal acetyl group, wherein the proislet peptide is selected from the group consisting of an HIP1 peptide (SEQ ID NO: 3), HIP2 peptide (SEQ ID NO: 4), HIP3 peptide (SEQ ID NO: 2), human REG3A peptide (SEQ ID NO: 30), human REG3G peptide (SEQ ID NO: 81), human REG1A peptide (SEQ ID NO: 67), human REG1B peptide (SEQ ID NO: 68), human REG4 peptide (SEQ ID NO: 85), hamster INGAP peptide (SEQ ID NO: 27, 32, 39, or 46), hamster REG2 peptide (SEQ ID NO: 72), hamster REG3G peptide (SEQ ID NO: 80), rat REG1 peptide (SEQ ID NO: 69), rat PAP/REG3B peptide (SEQ ID NO: 74), rat PAP3 peptide (SEQ ID NO: 75), rat REG3G peptide (SEQ ID NO: 79), mouse REG I peptide (SEQ ID NO: 70), mouse REG2 peptide (SEQ ID NO: 71), mouse REG3A peptide (SEQ ID NO: 33, 40, 47, or 53), mouse REG3B peptide (SEQ ID NO: 77), mouse REG3G peptide (SEQ ID NO: 78), mouse REG3S peptide (SEQ ID NO: 82), mouse REG4 peptide (SEQ ID NO: 86), bovine PTP peptide (SEQ ID NO: 83), Norway rat REG3 peptide (SEQ ID NO: 34, 41, 48, or 54), chimpanzee peptide according to SEQ ID NO: 31, chimpanzee peptide according to SEQ ID No 38, chimpanzee peptide according to SEQ ID No 45, chimpanzee peptide according to SEQ ID No 52, chimpanzee peptide according to SEQ ID No 60, bovine peptide according to SEQ ID NO:35, bovine peptide according to SEQ ID NO:42, bovine peptide according to SEQ ID NO:49, bovine peptide according to SEQ ID NO:55, bovine peptide according to SEQ ID NO:88, canine peptide according to SEQ ID NO:36, canine peptide according to SEQ ID NO:43, canine peptide according to SEQ ID NO:50, canine peptide according to SEQ ID NO:56, ovine peptide according to SEQ ID NO:37, ovine peptide according to SEQ ID NO:44, ovine peptide according to SEQ ID NO:51, and ovine peptide according to SEQ ID NO:57 
     
     
         14 . The peptide of  claim 13 , wherein said peptide comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO:7, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 23, SEQ ID NO: 24 and SEQ ID NO: 25. 
     
     
         15 . A pharmaceutical composition comprising a peptide of  claim 13  and a pharmaceutically acceptable excipient. 
     
     
         16 . The pharmaceutical composition of  claim 15 , wherein the composition comprises a therapeutically effective amount of the peptide. 
     
     
         17 . The pharmaceutical composition of  claim 15 , wherein said therapeutically effective amount is from 0.5 to 5 mg/kg. 
     
     
         18 . A pharmaceutical composition comprising a peptide of  claim 14  and a pharmaceutically acceptable excipient. 
     
     
         19 . The pharmaceutical composition of  claim 18 , wherein the composition comprises a therapeutically effective amount of the peptide. 
     
     
         20 . The pharmaceutical composition of  claim 18 , wherein said therapeutically effective amount is from 0.5 to 5 mg/kg. 
     
     
         21 . The pharmaceutical composition of  claim 18 , wherein the modified peptide comprises SEQ ID NO: 7. 
     
     
         22 . The pharmaceutical composition of  claim 21 , wherein the modified peptide consists essentially of SEQ ID NO: 7. 
     
     
         23 . A method of stimulating islet neogenesis or stimulating pancreatic islet cell regeneration in a subject in need thereof comprising administering to the subject a peptide of  claim 13 . 
     
     
         24 . A method of stimulating islet neogenesis or stimulating pancreatic islet cell regeneration in a subject in need thereof comprising administering to the subject a peptide of  claim 14 . 
     
     
         25 . The method of  claim 24 , wherein the peptide comprises SEQ ID NO: 7. 
     
     
         26 . The method of  claim 24 , wherein the peptide consists essentially of SEQ ID NO: 7. 
     
     
         27 . A method of treating diabetes in a subject in need thereof comprising administering to the subject a peptide of  claim 13 . 
     
     
         28 . The method of  claim 27 , wherein the peptide comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO:7, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 23, SEQ ID NO: 24 and SEQ ID NO: 25. 
     
     
         29 . The method of  claim 28 , wherein the peptide comprises SEQ ID NO: 7. 
     
     
         30 . The method of  claim 29 , wherein the peptide consists essentially of SEQ ID NO: 7. 
     
     
         31 . The method of  claim 27 , where the diabetes is type 2 diabetes. 
     
     
         32 . The method of  claim 27 , wherein the peptide is administered in a dose is from 0.5 to 5 mg/kg.