Methods and Assays for Detecting and Treating Hypoglycemia

Abstract

Methods for regulating glucagon release and of treating hypoglycemia, and for screening drug candidates for treating hypoglycemia. The methods are useful for treating diabetes mellitus and screening drug candidates for potential efficacy.

1 . A method of treating hypoglycemia comprising administering an effective amount of a compound that activates an ionotropic glutamate receptor to stimulate glucagon release. 
     
     
         2 . The method of  claim 1 , wherein the compound activates the glutamate receptor subunit GluR6. 
     
     
         3 . The method of  claim 1 , wherein the ionotropic glutamate receptor is a AMPA/kainatc type receptor. 
     
     
         4 . The method of  claim 1 , wherein the compound is selected from the group consisting of kainate, AMPA, and (2S,4R)-4-Methylglutamic acid, (RS)-2-Amino-3-(4-chloro-3-hydroxy-5-isoxazolyl)propionic acid, 4,6-Bis(benzoylamino)-1,3-benzenedicarboxylic acid, (±)-4-(4-Aminophenyl)-1,2-dihydro-1-methyl-2-propylcarbamoyl-6,7-methylenedioxyphthalazine, 1-(4′-Aminophenyl)-3,5-dihydro-7,8-dimethoxy-4H-2,3-benzodiazepin-4-one, 1,4-Dihydro-6-(1H-imidazol-1-yl)-7-nitro-2,3-quinoxalinedione hydrochloride, GABA, and Bicuculline. 
     
     
         5 . The method of  claim 1 , wherein the compound is a glutamate analog. 
     
     
         6 . The method of  claim 1 , wherein the compound is administered at a dose of about 5 mg/kg/day to about 200 mg/kg/day. 
     
     
         7 . The method of one of the preceding claims, wherein the hypoglycemia is associated with diabetes mellitus. 
     
     
         8 - 14 . (canceled)