Methods And Compositions Relating To Islet Cell Neogenesis

Abstract

The present invention provides methods and kits for treating diseases and conditions associated with impaired pancreatic function. The present invention further provides methods of stimulating islet cell neogenesis and stimulating islet cell differentiation from progenitor cells.

1 . A method of stimulating islet cell neogenesis in a subject in need thereof, comprising administering to said subject a therapeutically effective amount of a peptide comprising an unmodified HIP2 peptide sequence. 
     
     
         2 . The method of  claim 1 , wherein the total islet number is increased by at least 50% in the subject as compared to prior to the administration of the peptide comprising an unmodified HIP2 peptide sequence. 
     
     
         3 . The method of  claim 1 , further comprising administering a therapeutically effective amount of an agent selected from the group consisting of: an immune therapy agent and an additional agent that stimulates islet cell regeneration. 
     
     
         4 . The method of  claim 3 , wherein said immune therapy agent is selected from the group consisting of: anti-CD3 antibody, sirolimus, tacrolimus, heat-shock protein 60, an anti-glutamic acid decarboxylase 65 vaccine, mycophenolate mofetil, an anti-CD20 agent, rituximab, campath-1H, lysofylline, vitamin D, IBC-VSO vaccine, interferon-alpha, and a vaccine using CD4 + CD25 +  antigen-specific regulatory T cells. 
     
     
         5 . The method of  claim 3 , wherein said additional agent that stimulates islet cell regeneration is selected from the group consisting of: amylin, pramlintide, insulin, exendin-4, GIP, GLP-1, GLP-1 receptor agonists, GLP-1 analogs, hamster INGAP peptide and related peptides, liraglutide, and a dipeptidyl peptidase inhibitor which blocks the degradation of GLP-1. 
     
     
         6 . The method of  claim 3 , wherein the total islet number is increased by at least 50% in the subject as compared to prior to the administration of the peptide comprising an unmodified HIP2 peptide sequence. 
     
     
         7 . A method of treating a disease or condition associated with impaired pancreatic function in a subject in need thereof, comprising administering to said subject a therapeutically effective amount of a peptide comprising an unmodified HIP2 peptide sequence. 
     
     
         8 . The method of  claim 7 , wherein said disease or condition associated with impaired pancreatic function is selected from the group consisting of: type 1 diabetes, new onset type 1 diabetes, type 2 diabetes, Latent Autoimmune Diabetes in Adults, pre-diabetes, impaired fasting glucose, fasting hyperinsulinemia, impaired glucose tolerance, insulin resistant syndrome, insulin deficiency, metabolic syndrome, obesity, anorexia, bulimia, neuropathic pain, pancreatitis, pancreatic cancer, hyperlipidemia, hypertriglyceridemia, eating disorders, anovulatory cycles, lack of or diminished insulin production resulting in aberrant glucose metabolism, and polycystic ovarian syndrome. 
     
     
         9 . The method of  claim 8 , wherein said disease or condition associated with impaired pancreatic function is selected from the group consisting of: type 1 diabetes, type 2 diabetes, Latent Autoimmune Diabetes in Adults, pre-diabetes, and metabolic syndrome. 
     
     
         10 . The method of  claim 7 , further comprising administering a therapeutically effective amount of an agent selected from the group consisting of: an immune therapy agent and an additional agent that stimulates islet cell regeneration. 
     
     
         11 . The method of  claim 10 , wherein said immune therapy is selected from the group consisting of: anti-CD3 antibodies, sirolimus, tacrolimus, a heat-shock protein 60, an anti-glutamic acid decarboxylase 65 vaccine, mycophenolate mofetil alone or in combination with daclizumab, an anti-CD20 agent, rituximab, campath-1H, lysofylline, vitamin D, IBC-VSO vaccine, interferon-alpha, and a vaccine using CD4 + CD25 +  antigen-specific regulatory T cells. 
     
     
         12 . The method of  claim 10 , wherein said additional agent that stimulates islet cell regeneration is selected from the group consisting of: a HIP or a HIP-related peptide, amylin, pramlintide, insulin, exendin-4, GIP, GLP-1, GLP-1 receptor agonists, GLP-1 analogs, hamster INGAP peptide and related peptides, liraglutide, and a dipeptidyl peptidase inhibitor which blocks the degradation of GLP-1. 
     
     
         13 . The method of  claim 10 , wherein said disease or condition associated with impaired pancreatic function is selected from the group consisting of: type 1 diabetes, new onset type 1 diabetes, type 2 diabetes, Latent Autoimmune Diabetes in Adults, pre-diabetes, impaired fasting glucose, fasting hyperinsulinemia, impaired glucose tolerance, insulin resistant syndrome, insulin deficiency, metabolic syndrome, obesity, anorexia, bulimia, neuropathic pain, pancreatitis, pancreatic cancer, hyperlipidemia, hypertriglyceridemia, eating disorders, anovulatory cycles, lack of or diminished insulin production resulting in aberrant glucose metabolism, and polycystic ovarian syndrome. 
     
     
         14 . The method of  claim 13 , wherein said disease or condition associated with impaired pancreatic function is selected from: type 1 diabetes, type 2 diabetes, Latent Autoimmune Diabetes in Adults, pre-diabetes, and metabolic syndrome. 
     
     
         15 . A method of reducing insulin requirements in a subject in need thereof, comprising administering to said subject a therapeutically effective amount of a peptide comprising an unmodified HIP2 peptide sequence. 
     
     
         16 . The method of  claim 15 , further comprising administering a therapeutically effective amount of an agent selected from the group consisting of: an immune therapy agent and an additional agent that stimulates islet cell regeneration. 
     
     
         17 . The method of  claim 16 , wherein said immune therapy is selected from the group consisting of: anti-CD3 antibodies, sirolimus, tacrolimus, a heat-shock protein 60, an anti-glutamic acid decarboxylase 65 vaccine, mycophenolate mofetil alone or in combination with daclizumab, an anti-CD20 agent, rituximab, campath-1H, lysofylline, vitamin D, IBC-VSO vaccine, interferon-alpha, and a vaccine using CD4 + CD25 +  antigen-specific regulatory T cells. 
     
     
         18 . The method of  claim 16 , wherein said additional agent that stimulates islet cell regeneration is selected from: a HIP or a HIP-related peptide, amylin, pramlintide, insulin, exendin-4, GIP, GLP-1, GLP-1 receptor agonists, GLP-1 analogs, hamster INGAP peptide and related peptides, liraglutide, and a dipeptidyl peptidase inhibitor which blocks the degradation of GLP-1. 
     
     
         19 - 22 . (canceled) 
     
     
         23 . The method of  claim 1 , wherein the subject has diabetes. 
     
     
         24 . The method of  claim 7 , wherein the subject has diabetes.