Method for modulating insulin-independent glucose transport using teneurin c-terminal associated peptide (tcap)

Abstract

This invention relates to a method of increasing energy available to skeletal muscle cells comprising administering to the cells an effective amount of Tenurin C-terminal Associated Peptide (TCAP). The invention provides the use of TCAP to enhance muscle performance or recovery after injury as well as to prevent and/or treat a number of conditions including insulin resistance, type II diabetes, hypoxia and glycogen storage diseases.

1 : A method of increasing energy available to skeletal muscle cells, the method comprising administering to a patient in need thereof an effective amount of an isolated teneurin c-terminal associated peptide (TCAP peptide), or a pharmaceutically acceptable salt thereof, wherein the amino acid sequence of said TCAP peptide consists essentially of:
 (i) an amino acid sequence having at least 95% identity to an amino acid sequence selected from the group consisting of SEQ ID NOs: 13, 14, 21, 22, 29, 30, 37, 38, 45, 46, 53, 54, 61, 62, 69, 70, 77, 78, 85, 86, 93, 94, and 101; or   (ii) a 38 amino acid sequence from the carboxy terminal end of a peptide having at least 95% identity to an amino acid sequence selected from the group consisting of SEQ ID NOs: 13, 14, 21, 22, 29, 30, 37, 38, 45, 46, 53, 54, 61, 62, 69, 70, 77, 78, 85, 86, 93, 94, and 101;   optionally wherein:   (a) the carboxy terminal end of said TCAP peptide is amidated or comprises an amidation signal sequence; and/or   (b) when the amino terminal amino acid of said TCAP peptide is glutamine, it is in the form of pyroglutamic acid.   
     
     
         2 : The method of  claim 1 , wherein increasing energy available to skeletal muscle cells comprises increasing glucose uptake by skeletal muscle cells under conditions where increased intracellular glucose in skeletal muscle cells is advantageous. 
     
     
         3 : The method of  claim 1 , for increasing energy available to skeletal muscle cells under conditions where increased energy available to skeletal muscle cells is advantageous. 
     
     
         4 : The method of  claim 3 , wherein the conditions where increased energy available to muscle cells is advantageous is a condition in which the skeletal muscle cells exhibit insulin resistance. 
     
     
         5 : The method of  claim 3 , wherein the conditions where increased energy available to muscle cells is advantageous is type 2 diabetes. 
     
     
         6 : The method of  claim 3 , wherein the conditions where increased energy available to muscle cells is advantageous are immediately before, during, or immediately after exercise. 
     
     
         7 : The method of  claim 3 , wherein the conditions where increased energy available to muscle cells is advantageous is selected from the group consisting of: hypoxia, injury, a glycogen storage disorder, and a myopathy. 
     
     
         8 : The method of  claim 1 , wherein the increased energy is available for at least one day. 
     
     
         9 : The method of  claim 1 , wherein the increased energy is available for at least three days. 
     
     
         10 : The method of  claim 1 , wherein the increased energy is available for at least five days. 
     
     
         11 : The method of  claim 1 , wherein the increased energy is available for at least seven days. 
     
     
         12 - 24 . (canceled) 
     
     
         25 : The method of  claim 1  for preventing and/or treating Type-2 diabetes. 
     
     
         26 : The method of  claim 1 , wherein the peptide is administered to a patient with Type 1 or Type 2 diabetes. 
     
     
         27 : The method of  claim 1 , wherein the TCAP peptide is administered or a pharmaceutical composition comprising the peptide is administered. 
     
     
         28 : The method of  claim 1  wherein the TCAP peptide or a pharmaceutical composition comprising the TCAP peptide is administered and the TCAP peptide consists essentially of:
 (i) an amino acid sequence having at least 95% identity to an amino acid sequence consisting of SEQ ID NOs: 38 or 70; 
 optionally wherein:
 (a) the carboxy terminal end of said TCAP peptide is amidated or comprises an amidation signal sequence; and/or 
 (b) when the amino terminal amino acid of said TCAP peptide is glutamine, it is in the form of pyroglutamic acid. 
 
 
     
     
         29 : The method of  claim 28 , wherein the amino acid sequence of the TCAP peptide consists essentially of an amino acid sequence consisting of SEQ. ID. NOs: 38 or 70. 
     
     
         30 : The method of  claim 28 , wherein administration is to a patient to whom increased energy available to muscle cells is advantageous and/or to a patient who has a condition in which the skeletal muscle cells exhibit insulin resistance and/or to a patient to whom increased intracellular glucose in skeletal muscle cells is advantageous. 
     
     
         31 : The method of  claim 30  for the prevention and/or treatment of type 2 diabetes. 
     
     
         32 : The method of  claim 30 , wherein increased energy available to muscle cells is advantageous immediately before, during, or immediately after exercise. 
     
     
         33 : The method of  claim 30 , wherein increased energy available to muscle cells is advantageous in conditions selected from the group consisting of: hypoxia, injury, a glycogen storage disorder, and a myopathy.