Method of Regulating Glucose Metabolism, and Reagents Related Thereto

Abstract

The present invention provides methods and compositions for modification and regulation of glucose and lipid metabolism, generally to reduce insulin resistance, hyperglycemia, hyperinsulinenmia, obesity, hyperlipidemia, hyperlipoprotein-emia (such as chylomicrons, VLDL and LDL), and to regulate body fat and more generally lipid stores, and, more generally, for the improvement of metabolism disorders, especially those associated with diabetes, obesity and/or atherosclerosis.

1 - 38 . (canceled) 
     
     
         39 . A method for treating Type II diabetes, comprising administering orally to an animal in need thereof a therapeutically effective amount of an inhibitor of dipeptidylpeptidase IV (DPIV) or a pharmaceutically acceptable salt thereof once daily, wherein the inhibitor has a Ki for inhibition of DPIV in the nanomolar or less range; the duration of the therapeutic effect is at least about 24 hours; and the inhibitor is administered in an amount sufficient to increase the plasma half-life of glucagon-like peptide 1 (GLP-1) but not sufficient to suppress the immune system of the animal. 
     
     
         40 . The method of  claim 39 , wherein the inhibitor has a Ki for inhibition of DPIV of 10 nM or less. 
     
     
         41 . The method of  claim 39 , wherein the inhibitor has a Ki for inhibition of DPIV of 1.0 nM or less. 
     
     
         42 . The method of  claim 41 , wherein the inhibitor has a Ki for inhibition of DPIV of 0.1 nM or less. 
     
     
         43 . The method of  claim 39 , wherein the inhibitor has an EC 50  for immunosuppression in the μM or greater range. 
     
     
         44 . The method of  claim 39 , wherein the inhibitor has a molecular weight less than 1000 amu. 
     
     
         45 . The method of  claim 39 , wherein the animal is a mammal. 
     
     
         46 . The method of  claim 45 , wherein the mammal is a human. 
     
     
         47 . The method of  claim 39 , wherein the inhibitor is administered in a solid dosage form. 
     
     
         48 . The method of  claim 47 , wherein the solid dosage form is a tablet, capsule or pill. 
     
     
         49 . The method of  claim 39 , wherein the solid dosage form is a coated tablet. 
     
     
         50 . The method of  claim 39 , wherein the animal is a human; and the inhibitor has a molecular weight less than 1000 amu. 
     
     
         51 . The method of  claim 39 , wherein the animal is a human; and the inhibitor is administered in the form of a tablet. 
     
     
         52 . The method of  claim 39 , wherein the animal is a human; the inhibitor is administered in the form of a coated tablet; and the inhibitor has a molecular weight less than 1000 amu. 
     
     
         53 . The method of  claim 39 , wherein the animal is a human; and the inhibitor is administered in the form of a tablet, capsule or pill. 
     
     
         54 . The method of  claim 39 , wherein the animal is a human; and the inhibitor is administered in the form of a tablet. 
     
     
         55 . The method of  claim 39 , wherein the animal is a human; and the inhibitor is administered in the form of a coated tablet. 
     
     
         56 . The method of  claim 39 , wherein the animal is a human; the inhibitor is administered in the form of a tablet, capsule or pill; and the inhibitor has a molecular weight less than 1000 amu. 
     
     
         57 . The method of  claim 39 , wherein the animal is a human; the inhibitor is administered in the form of a tablet; and the inhibitor has a molecular weight less than 1000 amu. 
     
     
         58 . The method of  claim 39 , wherein the animal is a human; the inhibitor is administered in the form of a coated tablet; and the inhibitor has a molecular weight less than 1000 amu.