Peptides, derivatives and analogs thereof, and methods of using same

Abstract

Human proIslet Peptides (HIP) and HIP analogs and derivatives thereof, derived from or homologous in sequence to the human REG3A protein, chromosome 2p12, are able to induce islet neogenesis from endogenous pancreatic progenitor cells. Human proIslet Peptides are used either alone or in combination with other pharmaceuticals in the treatment of type 1 and type 2 diabetes and other pathologies related to aberrant glucose, carbohydrate, andor lipid metabolism, insulin resistance, overweight, obesity, polycystic ovarian syndrome, eating disorders and the metabolic syndrome.

We claim: 
     
         1 . A method of treating a pathology associated with impaired pancreatic function in a subject in need thereof comprising:
 administering to the subject a therapeutically effective amount of a human proislet peptide comprising an amino acid sequence of WIGLHDP (SEQ ID NO: 6).   
     
     
         2 . The method of  claim 1 , wherein the pathology is selected from pre-diabetes, type 2 diabetes, latent autoimmune diabetes, and hyperglycemia. 
     
     
         3 . The method of  claim 1  further comprising the step of administering one or more agents for stimulating pancreatic islet cell regeneration. 
     
     
         4 . The method of  claim 3 , wherein the agent for stimulating pancreatic islet cell regeneration is selected from a member of the group consisting of human proislet peptide, amylin, pramlinitide, exendin-4, liraglutide, GLP-1 receptor agonists, GLP-1, hamster INGAP, GIP, dipeptydyl peptidase-4 inhibitors and analogs thereof. 
     
     
         5 . The method of  claim 1  further comprising the step of administering one or more agents that inhibit autoimmune cells that target pancreatic islet cells. 
     
     
         6 . The method of  claim 5 , wherein the agent that inhibits the autoimmune cells that target pancreatic islet cells is selected from the group consisting of anti-CD3 antibody, rapamycin, FK506, heat-shock protein, tacrolimus, GAD65 vaccine, mycophenolate mofetil, lysofylline, rituximab, daclizumab, anti-CD52 antibody, anti-CD20 antibody, Vitamin D, IBC-VSO vaccine, interferon alpha and CD4+CD25+ antigen-specific regulatory T cells. 
     
     
         7 . The method of  claim 6 , wherein the vitamin D is vitamin D3. 
     
     
         8 . The method of  claim 7 , wherein the vitamin D3 is administered to the subject in an amount effective to maintain 25-hydroxy vitamin D above about 40 ngmL in the subject. 
     
     
         9 . The method of  claim 1 , wherein at least one symptom of the pathology associated with impaired pancreatic function is treated as a result of the administration of at least one human proislet peptide. 
     
     
         10 . The method of  claim 9 , wherein the symptom is selected from a member of the group consisting of frequent urination, excessive thirst, extreme hunger, unusual weight loss, increased fatigue, irritability, blurry vision, genital itching, odd aches and pains, dry mouth, dry or itchy skin, impotence, vaginal yeast infections, poor healing of cuts and scrapes, excessive or unusual infections, hyperglycemia, loss of glycemic control, fluctuations in postprandial blood glucose, fluctuations in blood glucagons and fluctuations in blood triglycerides. 
     
     
         11 . The method of  claim 1 , wherein the subject is a mammal. 
     
     
         12 . The method of  claim 11 , wherein the mammal is selected from a human, a horse, a cow, a sheep, a dog and a cat. 
     
     
         13 . The method of  claim 1 , wherein the peptide consists essentially of SEQ ID NO: 6. 
     
     
         14 . The method of  claim 1 , wherein the peptide comprises a chemically modified peptide comprising SEQ ID NO: 6. 
     
     
         15 . The method of  claim 1 , wherein the peptide is a fusion peptide comprising SEQ ID NO: 6. 
     
     
         16 . The method of  claim 1 , wherein the peptide is administered in a pharmaceutical composition. 
     
     
         17 . The method of  claim 1 , wherein the peptide is administered to said subject by a route selected from orally, subcutaneously, transdermally, intranasally, parenterally, topically and buccally. 
     
     
         18 . The method of  claim 1  further comprising administering insulin. 
     
     
         19 . The method of  claim 1 , wherein said human proislet peptide is conjugated to a compound selected from albumin, transferrin and polyethylene glycol.