It has been generally believed for some time that there is a dynamic balance and stoichiometry between oxygen consumption and glucose utilization to meet the brain's energy demands to support its functional activity. This concept has recently been challenged because of studies reporting that glucose utilization is stoichiometrically in excess of oxygen consumption during and following cognitive challenges or sensory stimulation. It is now a common speculation that functional activity in brain is supported by energy derived from glycolysis and little, if at all, from oxidative metabolism. Under conditions of limited oxygen supply, this would be expected, but for this to happen in the presence of adequate oxygen violates traditional concepts about energy metabolism. We have, therefore, examined in vivo the metabolism of [14C]glucose in rat brain in conditions in which glucose consumption was increased by functional activation. We found that labeling of the brain lactate pool was increased 3-fold during K+- stimulated metabolic activity. About 20% of the glucose taken up by brain was lost to the blood as lactate, and similar quantities must have been transported from activated tissue to other brain regions. Thus, trafficking of intermediary metabolites within the brain can be extensive, a new, unexpected finding. On the other hand, during and following sensory stimulation lactate accumulation in the brain and loss to the blood were much smaller even though the oxygen/glucose uptake ratio was reduced, indicating that glucose utilization exceeded the stoichiometric equivalent of the oxygen consumption. We found, however, that glycogen, which is localized mainly in glial cells, is depleted by sensory functional activation, indicating that some, if not all, of the excess glucose utilization that persists following the functional activation can be explained by the diversion of glucose carbon to the replenishment of metabolic pools depleted by the energy demands of the functional and metabolic activation's.
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