Method of Restoring the Incretin Effect

Abstract

The present invention relates to methods of treating metabolic syndrome, Type 2 diabetes mellitus, atherogenic dyslipidemia and/or obesity. The present invention a so relates to methods of restoring the incretin effect, to restoring physiologic control of glucagon levels, to restoring first-phase insulin secretion, and to restoring the physiologic glucose-dependent insulin secretion. The methods of the present invention comprise administration of a selective κ-receptor antagonist, such as guanidinylated naltrindole (GNTI), or pharmaceutically acceptable derivatives thereof to a subject in need thereof.

What is claimed is: 
     
         1 . A method of treating type 2 diabetes mellitus comprising administering to a subject a therapeutically effective amount of a selective κ-receptor antagonist, or a pharmaceutically acceptable derivative thereof. 
     
     
         2 . The method of  claim 1 , wherein the selective κ-receptor antagonist is GNTI. 
     
     
         3 . The method of  claim 1 , wherein the selective κ-receptor antagonist is administered weekly or daily. 
     
     
         4 . The method of  claim 3 , wherein the selective κ-receptor antagonist is administered weekly in an amount from about 30 ng to about 300 ng per kg of body weight weekly. 
     
     
         5 . The method of  claim 3 , wherein the selective κ-receptor antagonist is administered daily in an amount from about 8 ng to about 80 ng per kg of body weight daily. 
     
     
         6 . The method of  claim 1 , wherein the selective κ-receptor antagonist is administered sublingually, orally, enterally, parenterally, topically, systemically or injected intravascularly, subcutaneously, peritoneally. 
     
     
         7 . The method of  claim 1 , further comprising co-administration of an effective amount of an insulinogenic agent. 
     
     
         8 . The method of  claim 7 , wherein the insulinogenic agent is an extended release composition. 
     
     
         9 . The method of  claim 1 , wherein a μ-agonist is not co-administered.