Insulin-induced
hypoglycemia in normothermic rats caused progressive neurological depression and differentially altered regional cerebral
acetylcholine metabolism. Reductions of plasma
glucose from 7.7 mM (control) to 2.5-1.7 mM (moderate
hypoglycemia associated with decreased motor activity) or 1.5 mM (severe
hypoglycemia with
lethargy progressing to stupor) decreased
glucose concentrations in the cerebral cortex, striatum, and hippocampus to less than 10% of control. Moderate
hypoglycemia diminished
acetylcholine concentrations in cortex and striatum (21% and 45%, respectively) and reduced [1-2H2, 2-2H2]
choline incorporation into
acetylcholine (62% and 41%, respectively). Severe
hypoglycemia did not reduce the
acetylcholine concentration or synthesis in cortex and striatum further. The concentrations of
choline rose in the cortex (+53%) and striatum (+130%) of animals that became stuporous but a similar rise in [1-2H2, 2-2H2]
choline left the specific activities of
choline in these structures unchanged. Even severe
hypoglycemia did not alter the hippocampal
cholinergic system. In rats that developed
hypoglycemic stupor and were then treated with
glucose, the animals recovered apparently normal behavior, and the concentrations of
acetylcholine and the incorporation of [1-2H2, 2-2H2]-
choline into
acetylcholine returned to control values in the striatum but not in the cerebral cortex. Thus, impaired
acetylcholine metabolism in selected regions of the brain may contribute to the early symptoms of neurological dysfunction in
hypoglycemia.