Methods for preventing or treating insulin resistance

Abstract

The invention provides methods of preventing or treating insulin resistance in a mammalian subject. The methods comprise administering to the subject an effective amount of an aromatic-cationic peptide having at least one net positive charge; a minimum of four amino acids; a maximum of about twenty amino acids; a relationship between the minimum number of net positive charges (p m ) and the total number of amino acid residues (r) wherein 3p m is the largest number that is less than or equal to r+1; and a relationship between the minimum number of aromatic groups (a) and the total number of net positive charges (p t ) wherein 2a is the largest number that is less than or equal to p t +1, except that when a is 1, p t may also be 1.

1 . A method of treating or preventing insulin resistance in a mammalian subject, comprising administering to said mammalian subject a therapeutically effective amount of the peptide D-Arg-2′6′Dmt-Lys-Phe-NH 2  (SS-31). 
     
     
         2 . The method of  claim 1 , wherein the subject is a human. 
     
     
         3 . The method of  claim 1 , wherein the subject is suffering from diet-induced insulin resistance. 
     
     
         4 . The method of  claim 1 , wherein the insulin resistance is associated with type II diabetes. 
     
     
         5 . The method of  claim 1 , wherein the insulin resistance is associated with obesity. 
     
     
         6 . The method of  claim 1 , wherein the insulin resistance is associated with coronary artery disease, renal dysfunction, atherosclerosis, hyperlipidemia, essential hypertension, or fatty liver. 
     
     
         7 . The method of  claim 1 , wherein the insulin resistance is drug-induced insulin resistance. 
     
     
         8 . The method of  claim 1 , wherein the peptide is administered prior to the onset of type II diabetes. 
     
     
         9 . The method of  claim 1 , wherein the peptide is administered orally, topically, systemically, intravenously, subcutaneously, or intramuscularly. 
     
     
         10 . The method of  claim 1  further comprising the step of identifying the mammal in need of treating or preventing insulin resistance. 
     
     
         11 . The method of  claim 1  further comprising the step of monitoring the mammal for treatment or prevention of insulin resistance. 
     
     
         12 . The method of  claim 1 , wherein the therapeutically effective amount provides a concentration of peptide in a target tissue of about 10 −8  to 10 −6  molar.