Measurement of Local Cerebral Glucose Utilization and its Relation to Local Functional Activity in the Brain

  • Louis Sokoloff
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 291)


The average normal, human male brain represents approximately 2% of total body weight but consumes about 20% of the total body basal oxygen consumption (Sokoloff, 1989). The substrate for this high rate of energy metabolism is normally almost exclusively glucose (TABLE 1) (Sokoloff, 1960). In fact, more glucose is consumed than can be oxidized completely to carbon dioxide and water by the oxygen consumption, indicating that the glycolytic rate exceeds the rate of oxidation of the products of glycolysis, normally by about 20% (Table 1). The excess carbon derived from glycolytic utilization of glucose is probably distributed in many, e.g., lactate, pyruvate, and other intermediates of the glycolytic and tricarboxylic acid cycle pathways that leave the brain in amounts too insignificant to be detected in the cerebral blood, and also into several neurotransmitter pools, such as acetylcholine, glutamate, GABA, etc.


Operational Equation Glucose Utilization Hexose Transport Arterial Plasma Cerebral Glucose Utilization 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. DeFronzo, R.A., Tobin, J.D., Andres, R. (1979) Glucose clamp technique: a method for quantifying insulin secretion and resistance. Am. J. Physiol. 237: E214–E223.PubMedGoogle Scholar
  2. Dienel, G.A., Nelson, T., Cruz, N.F., Jay, T., Crane, A.M., and Sokoloff, L. (1988) Over-estimation of glucose-6-phosphatase activity in brain in vivo: Apparent difference in rates of [2-H]glucose and [U-14C]glucose utilization is due to contamination of precursor pool with C-labeled products and incomplete recovery of 14C-labeled metabolites. J. Biol. Chem. 263: 19697–19708.PubMedGoogle Scholar
  3. Fishman, R.S.and Karnovsky, M.L. (1986) Apparent absence of a translocase in the cerebral glucose-6-phosphatase system. J. Neurochem. 46: 371–378.PubMedCrossRefGoogle Scholar
  4. Gjedde, A. and Diemer, N.H. (1983) Autoradiographic determination of regional brain glucose content. J. Cereb. Blood Flow Metab. 4: 303– 310.CrossRefGoogle Scholar
  5. Goochee, C., Rasband, W.,and Sokoloff, L. (1980) Computerized densitometry and color-coding of [14C]deoxyglucose autoradiographs. Ann. Neurol. 7: 359–370.PubMedCrossRefGoogle Scholar
  6. Gottstein, U.U., Held, K., Müller, W., and Berghoff, W. (1972) Utilization of ketone bodies by the human brain. In: Research on the Cerebral Circulation. Fifth International Conference, 1970, J.S. Meyer, M. Reivich, H. Lechner, and O. Eichhorn, eds. Charles C. Thomas, Springfield, IL, pp. 137–145.Google Scholar
  7. Hers, H.G. (1957) Le Metablisme du Fructose. Editions Arscia, Bruxelles, p. 102.Google Scholar
  8. Kennedy, C., Des Rosiers, M.H., Reivich, M., Sharp, F., Jehle, J.W., and Sokoloff, L. (1975) Science ,187: 850–853.PubMedCrossRefGoogle Scholar
  9. Kennedy, C., Des Rosiers, M.H., Sakurada, O., Shinohara, M., Reivich, M., Jehle, J.W., and Sokoloff, L (1976) Metabolic mapping of the primary visual system of the monkey by means of the autoradiographic [14C]deoxyglucose technique. Proc. Natl. Acad. Sci., USA ,73: 4230–4234.PubMedCrossRefGoogle Scholar
  10. Kennedy, C., Sakurada, O., Shinohara, M., Jehle, J., and Sokoloff, L. (1978) Local cerebral glucose utilization in the normal conscious Macaque monkey. Ann. Neurol. 4: 293–301.PubMedCrossRefGoogle Scholar
  11. Kety, S.S. (1950) Circulation and metabolism of the human brain in health and disease. Am. J. Med. 8: 205–217.PubMedCrossRefGoogle Scholar
  12. Kety. S.S., Polis, B.D., Nadler, C.S., and Schmidt, C.F. (1948) Blood flow and oxygen consumption of the human brain in diabetic acidosis. J. Clin. Invest. 27: 500–510.CrossRefGoogle Scholar
  13. Kety, S.S. and Schmidt, C.F. (1948) The nitrous oxide method for the quantitative determination of cerebral blood flow in man: theory, procedure, and normal values. J. Clin. Invest. 27: 476–483.CrossRefGoogle Scholar
  14. Kety, S.S., Woodford, R.B., Harmel, M.H., Freyhan, F.A., Appel, K.E., and Schmidt, C.F. (1948) Cerebral blood flow and metabolism in schizophrenia. The effects of barbiturate semi-narcosis, insulin coma, and electroshock. AM. J. Psychiat. 104: 765–770.PubMedGoogle Scholar
  15. Krebs, H.A., Williamson, D.H., Bates, M.W., Page, M.A., and Hawkins, R.A. (1971) The role of ketone bodies in caloric homeostasis. Adv. Enzyme Regul. 9: 387–409.CrossRefGoogle Scholar
  16. Lucignani, G., Namba, H., Nehlig, A., Porrino, L. J., Kennedy, C., and Sokoloff, L. (1987) Effects of insulin on local cerebral glucose utilization in the rat. J. Cereb. Blood Flow Metab. 7: 309–314.PubMedCrossRefGoogle Scholar
  17. Mori, K., Schmidt, K., Jay, T., Palombo, E., Nelson, T., Lucignani, G., Pettigrew, K., Kennedy, C., and Sokoloff, L. (1990) Optimal duration of experimental period in measurement of local cerebral glucose utilization with the deoxyglucose method. J. Neurochem. 54: 307–319.PubMedCrossRefGoogle Scholar
  18. Namba, H., Lucignani, G., Nehlig, A., Patlak, C., Pettigrew, K., Kennedy, C., and Sokoloff, L. (1987) Effects of insulin on hexose transport across blood-brain barrier in normoglycemia. Am. J. Physiol. 252 (Endocrinol. Metab. 15): E299–303.PubMedGoogle Scholar
  19. Nelson T, Kaufman, E.E., and Sokoloff, L. (1984) 2-Deoxyglucose incorporation into rat brain glycogen during measurement of local cerebral glucose utilization by the 2-deoxyglucose method. J. Neurochem. 43: 949–956.PubMedCrossRefGoogle Scholar
  20. Nelson, T., Lucignani, G., Goochee, J., Crane, A. M., and Sokoloff, L. (1986) Invalidity of criticisms of the deoxyglucose method based on alleged glucose-6-phosphatase activity in brain. J. Neurochem. 46: 905–919.PubMedCrossRefGoogle Scholar
  21. Nelson, T., Dienel, G.A., Mori, K., Cruz, N.F., and Sokoloff, L. (1987) Deoxyglucose-6-phosphate stability in vivo and the deoxyglucose method: Response to comments of Hawkins and Miller. J. Neurochem. 49: 1949–1960.CrossRefGoogle Scholar
  22. Orzi, F., Lucignani, G., Dow-Edwards, D., Namba, H., Nehlig, A., Patlak, C. S., Pettigrew, K., Schuier, F., and Sokoloff, L. (1988) Local cerebral glucose utilization in controlled graded levels of hyperglycemia in the conscious rat. J. Cereb. Blood Flow Metab. 8: 346–356.PubMedCrossRefGoogle Scholar
  23. Owen, O.E., Morgan, A.P., Kemp, H.G., Sullivan, J.M., Herrera, M.G., and Cahill, G.F. (1967) Brain metabolism during fasting. J. Clin. Invest. 46: 1589–1595.PubMedCrossRefGoogle Scholar
  24. Phelps, M. E., Huang, S. C., Hoffman, E. J., Selin, C., Sokoloff, L., and Kuhl, D. E. (1979) Tomographic measurement of local cerebral glucose metabolic rate in humans with (F-18)2-fluoro-2-deoxy-D-glucose: validation of method. Ann. Neurol. 6: 371–388.PubMedCrossRefGoogle Scholar
  25. Reivich, M., Jehle, J., Sokoloff, L., Kety, S.S. (1969) Measurement of regional cerebral blood flow with antipyrine-C in awake cats. J. Appl. Physiol. 27: 296–300.PubMedGoogle Scholar
  26. Reivich, M., Kuhl, D., Wolf, A., Greenberg, J., Phelps, M., Ido, T., Cassella, V., Fowler, J., Hoffman, E., Alavi, A., Som, P., and Sokoloff, L. (1979) The [18F]fluoro-deoxyglucose method for the measurement of local cerebral glucose utilization in man. Circulation Res. 44: 127–137.PubMedGoogle Scholar
  27. Reivich, M., Alavi, A., Wolf, A., Fowler, J., Russell, J., Arnett, C., MacGregor, R. R., Shiue, C.Y., Atkins, H., Anand, A., Dann, R., and Greenberg, J.H. (1985) Glucose metabolic rate kinetic model parameter determination in humans: the lumped constants and rate 1 O 1 I constants for [18F]fluorodeoxyglucose and [11C]deoxyglucose. J. Cereb. Blood Flow Metab. 5: 179–192.PubMedCrossRefGoogle Scholar
  28. Schuier, F., Orzi, F., Suda, S., Lucignani, G., Kennedy, C., and Sokoloff, L. (1990) Influence of plasma glucose concentration on lumped constant of the deoxyglucose method: Effects of hyperglycemia in the rat. J. Cereb. Blood Flow Metab. In press.Google Scholar
  29. Sokoloff, L. (1960) Metabolism of the central nervous system in vivo. In: Handbook of Physiology -Neurophysiology, Vol. III ,J. Field, H.W. Magoun, and V.E. Hall, eds. American Physiological Society, Washington, D. C., pp. 1843–1864.Google Scholar
  30. Sokoloff, L. (1969) Cerebral circulation and behavior in man: strategy and findings. In: Psycho chemical Research in Man ,A.J.Mandell and M.P. Mandell, eds. Academic Press, New York City, pp. 237–252.Google Scholar
  31. Sokoloff, L. (1981) Localization of functional activity in the central nervous system by measurement of glucose utilization with radioactive deoxyglucose. J. Cereb. Blood Flow Metab. 1: 7–36.PubMedCrossRefGoogle Scholar
  32. Sokoloff, L. (1982) The radioactive deoxyglucose method: theory, procedure, and applications for the measurement of local glucose utilization in the central nervous system. In: Advances in N euro chemistry, Vol. 4 ,B.W. Agranoff and M.H. Aprison, eds. Plenum Publishing Corp., New York, pp. 1–82.Google Scholar
  33. Sokoloff, L. (1985) Basic principles in imaging of regional cerebral metabolic rates. In: Brain Imaging and Brain Function ,Research Publication of Association for Research in Nervous and Mental Disease, Vol. 63, L. Sokoloff, ed. Raven Press, New York, pp. 21–49.Google Scholar
  34. Sokoloff, L. (1989) Circulation and energy metabolism of the brain. In: Basic Neurochemistry, Fourth Edition ,G. Siegel, B. Agranoff, R.W. Albers, and P. Molinoff, eds. Raven Press, New York, pp. 565–590.Google Scholar
  35. Sokoloff, L., Mangold, R., Wechsler, R. L., Kennedy, C., and Kety, S.S. (1955) The effect of mental arithmetic on cerebral circulation and metabolism. J. Clin. Invest. 34: 1101–1108.PubMedCrossRefGoogle Scholar
  36. Sokoloff, L., Reivich, M., Kennedy, C., Des Rosiers, M.H., Patlak, C.S., Pettigrew, K.D., Sakurada, O., and Shinohara, M. (1977) The [ C]deoxyglucose method for the measurement of local cerebral glucose utilization: theory, procedure, and normal values in the conscious and anesthetized albino rat. J. Neurochem. 28: 897–916.PubMedCrossRefGoogle Scholar
  37. Sols, A. and Crane, R.K. (1954) Substrate specificity of brain hexokinase. J. Biol. Chem. 210: 581–595.PubMedGoogle Scholar
  38. Suda, S., Shinohara, M., Miyaoka, M., Lucignani, G., Kennedy, C., and Sokoloff, L. (1990) The lumped constant of the deoxyglucose method in hypoglycemia: Effects of moderate hypoglycemia on local cerebral glucose utilization in the rat. J. Cereb. Blood Flow Metab. In press.Google Scholar

Copyright information

© Plenum Press, New York 1991

Authors and Affiliations

  • Louis Sokoloff
    • 1
  1. 1.National Institute of Mental HealthBethesdaUSA

Personalised recommendations