Changes in Carbohydrate Substrates, Amino Acids and Ammonia in the Brain During Insulin‐induced Hypoglycemia

Abstract

—The influence of insulin‐induced hypoglycemia upon carbohydrate substrates, amino acids and ammonia in the brain was studied in lightly anaesthetized rats, and the changes observed were related to the blood glucose concentration and to the EEG. Calculations from glucose concentrations in tissue, CSF and blood indicated the presence of appreciable amounts of free intracellular glucose at blood glucose concentrations above 3 μmol/g. When the blood glucose concentration fell below 3 μmol/g, there was no calculated intracellular glucose and decreases in the concentrations of glycogen, G‐6‐P, pyruvate, lactate and of citric acid cycle intermediates were observed. At blood glucose levels of below 1 μmol/g the tissue was virtually depleted of glycogen, G‐6‐P, pyruvate and lactate. When the blood glucose concentration was reduced below about 2·5 μmol/g there were progressive increases in aspartate and progressive decreases in alanine, GABA, glutamine and glutamate, and at blood glucose concentrations below 2 μmol/g the ammonia concentration increased. It is suggested that most of the changes observed can be explained as a result of a decreased availability of pyruvate and of NADH. The decrease in the concentration of free NADH was reflected in reductions of the lactate/pyruvate and malate/oxaloacetate ratios at an unchanged intracellular pH. Slow wave activity appeared in the EEG when the hypoglycemia gave rise to reduction of the intracellular glucose concentration to zero. Convulsive activity continued until carbohydrate stores in the form of glycogen and G‐6‐P were depleted. When this occurred the EEG became isoelectric. In all convulsive animals the concentration of the nervous system activity inhibitor, GABA, was decreased and stimulant, aspartate, was increased.

Effects of insulin on blood, plasma, and brain glucose in hyperglycemic diabetic rats.

“…4 ' 17 -18 Similarly, when blood or plasma glucose decreases under the influence of insulin, brain glucose will also tend to decrease. 19 Data from the present study and from a recent study from our laboratory 9 supported these conclusions, but additionally demonstrated that for a given blood or plasma glucose concentration, diabetic rats had a greater concentration of glucose in the brain than did normoglycemic nondiabetic rats.…”

Role of Pyruvate Carboxylase in Facilitation of Synthesis of Glutamate and Glutamine in Cultured Astrocytes

“…However, a number of investigations suggest that in very severe hypoglycemia, the amount of glutamate in the brain falls (Lewis et a!., 1974;Gore!! et a!., 1976;Enge!sen and Fonnum, 1983), although very little decrease is observed when blood glucose levels are varied in the range compatible with normal brain function (Engelsen and Fonnum, 1983).…”

Nuclear magnetic resonance studies of the regulation of the pentose phosphate pathway

“…The concentration of creatine plus phosphosphocreatine in the brain was assumed to be 10.5 mM (14). From these observations, and assuming a linear relationship between concentration and SNR, and volume and SNR, we estimate that a proton species at a concentration of about 0.9 mM in a volume of 8 ml with 4 minutes of acquisition time at a field strength of 2.1 Tesla would yield a SNR of 5.…”