Labeling of Metabolic Pools by [6- 14 C]Glucose during K + -Induced Stimulation of Glucose Utilization in Rat Brain

[6-¹⁴C]Glucose is the tracer sometimes recommended to assay cerebral glucose utilization (CMR_glc) during transient or brief functional activations, but when used to study visual stimulation and seizures in other laboratories, it underestimated CMR_glc. The metabolic fate of [6-¹⁴C]glucose during functional activation of cerebral metabolism is not known, and increased labeling of diffusible metabolites might explain underestimation of CMR_glc and also reveal trafficking of metabolites. In the current studies cerebral cortex in conscious rats was unilaterally activated metabolically by KCl application, and CMR_glc was determined in activated and contralateral control cortex with [6-¹⁴C]glucose or 2-[¹⁴C]deoxyglucose ([¹⁴C]DG) over a 5- to 7-min interval. Local ¹⁴C concentrations were determined by quantitative autoradiography. Labeled precursor and products were measured bilaterally in paired cortical samples from funnel-frozen brains. Left-right differences in ¹⁴C contents were small with [6-¹⁴C]glucose but strikingly obvious in [¹⁴C]DG autoradiographs. CMR_glc determined with [6-¹⁴C]glucose was slightly increased in activated cortex but 40–80% below values obtained with [¹⁴C]DG. [¹⁴C]Lactate was a major metabolite of [6-¹⁴C]glucose in activated but not control cortex and increased proportionately with unlabeled lactate. These results demonstrate significant loss of labeled products of [6-¹⁴C]glucose from metabolically activated brain tissue and indicate that [¹⁴C]DG is the preferred tracer even during brief functional activations of brain.