Regional Amino Acid Distribution in Relation to Function in Insulin Hypoglycaemia

Abstract

The amino acids glutamate, aspartate, GABA and glutamine were measured as their dansyl derivatives in whole brain and specific brain regions by a sensitive double-labeling technique at various times during the development of hypoglycemic encephalopathy. Hypoglycemia was induced by administration of insulin (100 i.u./kg) to 24-h fasted rats. No significant changes in glutamate, GABA or glutamine were detected in whole brain at any time up to and including the onset of hypoglycemic convulsions. In cerebral cortex, GABA levels were reduced to 65% of normal prior to the appearance of neurological symptoms of hypoglycemia. Onset of symptoms (severe catalepsy and loss of righting reflex, but before the onset of convulsions) was accompanied by marked decreases of glutamate and glutamine in striatum and hippocampus. These regions, in addition to cerebral cortex, show the greatest vulnerability to hypoglycemic insult, according to previous anatomical studies. Aspartate levels were significantly increased (P < 0.01) in the cerebral cortex of convulsing animals, confirming a previous report. No changes were detectable in any of the amino acids studies in medulla-pons at any time during the progression of hypoglycemia. Cerebral cortex and striatum showed a selective net loss of amino acids (2.2 and 3.5 .mu.mol/g, respectively) prior to the onset of insulin-hypoglycemic convulsions.