Abstract
The metabolism of glucose in brains during sustained hypoglycemia was studied. [U-14C]Glucose (20 μCi) was injected into control rats, and into rats at 2.5 hr after a bolus injection of 2 units of insulin followed by a continuous infusion of 0.2 units/100 g rat/hr. This regimen of insulin injection was found to result in steady-state plasma glucose levels between 2.5 and 3.5 μmol per ml. In the brains of control rats carbon was transferred rapidly from glucose to glutamate, glutamine, γ-aminobutyric acid and aspartate and this carbon was retained in the amino acids for at least 60 min. In the brains of hypoglycemic rats, the conversion of carbon from glucose to amino acids was increased in the first 15 min after injection. After 15 min, the specific activity of the amino acids decreased in insulin-treated rats but not in the controls. The concentrations of alanine, glutamate, and γ-aminobutyric acid decreased, and the concentration of aspartate increased, in the brains of the hypoglycemic rats. The concentration of pyridoxal-5′-phosphate, a cofactor in many of the reactions whereby these amino acids are formed from tricarboxylic acid cycle intermediates, was less in the insulin-treated rats than in the controls. These data provide evidence that glutamate, glutamine, aspartate, and GABA can serve as energy sources in brain during insulin-induced hypoglycemia.
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References
Davidson, N. 1976. Neurotransmitter amino acids. Academic Press, New York.
Nemoto, E. M., Hoff, J. T., andSeveringhaus, J. W. 1974. Lactate uptake and metabolism by brain during hyperlactatemia and hypoglycemia. Stroke 5:48–53.
Krebs, H. A., Williamson, D. H., Bates, M. W., Page, M. A., andHawkins, R. A. 1971. The role of ketone bodies in caloric homeostasis. Adv. Enzyme Regul. 9:387–409.
Bollman, J. L. 1948. A cage which limits the activity of rats. J. Lab. Clin. Med. 33:1348.
Veech, R. L., andHawkins, R. A. 1974. Brain-blowing, a technique for in vivo study of brain metabolism. Pages 171–182,in Marks, N. andRodnight, R. (eds.), Research Methods in Neurochemistry, Vol. 2, Plenum Press, New York.
Wong, K. L., andTyce, G. M. 1978. Effect of the administration ofl-5-hydroxytryptophan and a monoamine oxidase inhibitor on glucose metabolism in rat brain. J. Neurochem. 31, 613–620.
Slein, M. W. 1965.d-Glucose: Determination with hexokinase and glucose-6-phosphate dehydrogenase. Pages 117–133,in Bergmeyer, H. U. (ed.), Methods of Enzymatic Analysis, Academic Press, New York.
Noll, F. 1974.l-Lactate: Determination with LDH, GPT, and NAD. Pages 1475–1479,in Bergmeyer, H. U. (ed.), Methods of Enzymatic Analysis, Academic Press, New York.
Nahorski, S. R., andRogers, K. J. (1972. An enzymic fluorometric micro method for determination of glycogen. Anal. Biochem. 49:492–497.
Chabner, B., andLivingston, D. 1970. A simple enzymic assay for pyridoxal phosphate. Anal. Biochem. 34:413–423.
Bayoumi, R. A., andSmith, W. R. D. 1976. Pyridoxal-5-phosphate levels in rat brain assayed by a modified method using enzymic decarboxylation ofl-[14C]tyrosine. J. Neurochem. 26:405–407.
Tyce, G. M. 1971. Effect of dihydroxyphenylalanine administered with a monoamine oxidase inhibitor on glucose metabolism in rat brain. Biochem. Pharmacol. 20, 2371–2384.
Tyce, G. M. 1976. The effect ofl-dopa and an inhibitor of peripheral decarboxylation on glucose metabolism in brain. J. Neurochem. 27:1397–1403.
Berl, S., andClarke, D. D. Compartmentation of amino acid metabolism. Pages 447–472,in Lajtha, A. (ed.), Handbook of Neurochemistry, Vol. II, Plenum Press, New York.
Kamp, C. W., Mursch, D. A., Stavinoha, W. B., andMedina, M. A. 1980. Measurement of mouse brain glucose utilization in vivo using [U-14C]glucose. Neurochem. Res. 5:61–67.
Hawkins, R. A., Miller, A. L., Cremer, J. E., andVeech, R. L.: Measurement of the rate of glucose utilization by rat brain in vivo. J. Neurochem. 23:917–923.
Flock, E. V., Tyce, G. M., andOwen, C. A., Jr. 1969. Glucose metabolism in brains of diabetic rats. Endocrinology 85:428–437.
Ensinck, J. W. andWilliams, R. H. 1974. Disorders causing hypoglycemia. Page 637,in Williams, R. H. (ed.), Textbook of Endocrinology, Fifth Edition, Saunders Company, Philadelphia.
Baker, N., Shipley, R. A., Clark, R. E., andIncefy, G. E. 1959.14C studies in carbohydrate metabolism: Glucose pool size and rate of turnover in the normal rat. Am. J. Physiol. 196:245–252.
DeRopp, R. S., andSnedecor, E. H. 1961. Effect of drugs on amino acid levels in the rat brain: hypoglycemic agents. J. Neurochem. 7:128–134.
Dittmer, D. 1981. Biological handbooks. Page 5, Blood and other body fluids. Federation of the American Society for Experimental Biology, Washington, D.C.
Tews, J. K., Carter, S. H., andStone, W. E. 1965. Chemical changes in the brain during insulin hypoglycaemia and recovery. J. Neurochem. 12:679–693.
Dawson, R. M. C. 1953. Cerebral amino acids in fluoroacetate-poisoned anaesthetized and hypoglycemic rats. Biochem. Biophys. Acta 11:548–552.
Gorell, J. M., Dolkart, P. H., andFerrendelli, J. A. 1976. Regional levels of glucose, amino acids, high energy phosphates, and cyclic nucleotides in the central nervous system during hypoglycemic stupor and behavioral recovery. J. Neurochem. 27, 1043–1049.
Toth, J., andLajtha, A. 1981. Drug-induced changes in the composition of the cerebral free amino acid pool. Neurochem. Res. 6:3–12.
Wong, K. L., andTyce, G. M. 1979. Pyridoxal 5′-phosphate levels in brain after treatments which impair cerebral glucose metabolism. Neurochem. Res. 4:821–826.
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Wong, KL., Tyce, G.M. Glucose and amino acid metabolism in rat brain during sustained hypoglycemia. Neurochem Res 8, 401–415 (1983). https://doi.org/10.1007/BF00965097
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DOI: https://doi.org/10.1007/BF00965097