2‐Deoxyglucose Incorporation into Rat Brain Glycogen During Measurement of Local Cerebral Glucose Utilization by the 2‐Deoxyglucose Method

Abstract

The incorporation of 14C into glycogen in rat brain has been measured under the same conditions that exist during the measurement of local cerebral glucose utilization by the autoradiographic 2-[14C]deoxyglucose method. The results demonstrate that approximately 2% of the total 14C in brain 45 min after the pulse of 2-[14C]deoxyglucose is contained in the glycogen portion, and, in fact, incorporated into alpha-1-4 and alpha-1-6 deoxyglucosyl linkages. When the brain is removed by dissection, as is routinely done in the course of the procedure of the 2-[14C]deoxyglucose method to preserve the structure of the brain for autoradiography, the portion of total brain 14C contained in glycogen falls to less than 1%, presumably because of postmortem glycogenolysis which restores much of the label to deoxyglucose-phosphates. In any case, the incorporation of the 14C into glycogen is of no consequence to the validity of the autoradiographic deoxyglucose method, not because of its small magnitude, but because 2-[14C]deoxyglucose is incorporated into glycogen via [14C]deoxyglucose-6-phosphate, and the label in glycogen represents, therefore, an additional "trapped" product of deoxyglucose phosphorylation by hexokinase. With the autoradiographic 2-[14C]deoxyglucose method, in which only total 14C concentration in the brain tissue is measured by quantitative autoradiography, it is essential that all the labeled products derived directly or indirectly from [14C]deoxyglucose phosphorylation by hexokinase be retained in the tissue; their chemical identity is of no significance.

In vivo 13C NMR studies of compartmentalized cerebral carbohydrate metabolism

“…Interestingly, at this point cerebral blood flow was increased abruptly, indicating an attempt by the brain to increase supply, by decreasing the arterio-venous gradient for glucose (Choi et al, 2001). We reported rates of label incorporation into glycogen using the native glucose that were very similar to those observed using deoxyglucose (Nelson et al, 1984), implying that the rate of incorporation of deoxyglucose into glycogen is as efficient as it is for glucose. These considerations raise the interesting possibility that deoxyglucose measurements of brain glucose metabolism can be affected by brain glycogen metabolism in focal neural activation.…”

Brain Glucose Metabolism in Noninsulin-Dependent Diabetes Mellitus: A Study in Pima Indians Using Positron Emission Tomography during Hyperinsulinemia with Euglycemic Glucose Clamp

“…Glycogen has been demonstrated by histochemistry in epithelia of the choroid plexus, ependyma of the ventricles including the median eminence and area postrema, cerebral endothelium, pericytes, and astrocytes, but is sparse or nonexistant in neurons (22,23). About 2% of brain [2-14 C]deoxyglucose radioactivity is in the form of glycogen in studies using the Sokoloff method of quantitative autoradiography (24). Biochemical studies show that brain glycogen may increase several-fold when hyperinsulinemia and hyperglycemia coexist, but not when the concentration of insulin is low (25).…”

Direct, noninvasive measurement of brain glycogen metabolism in humans

“…The biopsy samples were collected under conditions of surgery, therefore such investigations are not widely applicable, in addition to the fact that the results may be influenced by anesthesia. The postmortem studies, on the other hand, bear another challenge due to the well-known rapid postmortem breakdown of glycogen (Choi et al, 1999;Lowry et al, 1964;Nelson et al, 1984;Swanson et al, 1989). A recent study underlined the challenges associated with biochemical extraction of brain glycogen and suggested that previous studies may have underestimated its levels in resting rodent brain (Cruz and Dienel, 2002).…”