Table 3. Glycogen and glucose utilization during normal and pathophysiological conditions.
Mean glycogen utilization rates were either reported by the cited studies, calculated from net glycogen consumed during a specified time interval, or determined by MRS during and after labelling of brain glycogen with [1-13C]glucose. Glycogenolysis rates can be compared with mean local rates of glucose utilization in the same or related structures in a representative [14C]deoxyglucose study in normal resting rats. Comparisons are also made during ischaemia, when rates were calculated from changes in levels of energy metabolites.
| Substrate and brain structure | Rate (μmol·g−1·min−1) | Reference(s) |
|---|---|---|
| A. Glycogen utilization rate or label clearance rate | ||
| Rest, conscious mouse forebrain. Total glycogen | 0.010* | (Watanabe and Passonneau, 1973) |
| Limit dextrin (inner core) | 0.004 | |
| Rest, α-chloralose-anaesthetized rats, cerebral cortex/dorsal caudate labelled during hyperglycaemia | 0.008† | (Choi et al., 1999) |
| Rest, conscious euglycaemic human occipital cortex of normal subjects or Type 1 diabetics with hypoglycaemic unawareness | 0.003–0.005‡ | (Oz et al., 2007, 2009, 2012) |
| Sensory stimulation (5 min), conscious rat cerebral cortex | 0.58§ | (Cruz and Dienel, 2002) |
| Sensory stimulation (5 min)+15 min recovery | 0.20§ | |
| Sensory stimulation (10 min) cerebral cortex | 0.055§ | (Dienel et al., 2007a) |
| Hypoglycaemia, conscious rat forebrain during lethargy | 0.04–0.07‖ | (Ghajar et al., 1982) |
| Hypoglycaemia, conscious rat parietal cortex+hippocampus | 0.03¶ | (Suh et al., 2007) |
| Hypoglycaemia, conscious rat, three brain regions | 0.01–0.02§ | (Herzog et al., 2008) |
| Hypoglycaemia, glycogen degradation rate after insulin infusion into α-chloralose-anaesthetized rats | 0.038** | (Choi et al., 2003) |
| Hypoglycaemia, human occipital cortex | (Oz et al., 2009) | |
| Insulin-induced hypoglycaemia, 13C-washout rate | 0.002†† | |
| Euglycaemia, 13C-washout rate | 0.0005 | |
| Euglycaemia turnover rate (synthesis = degradation) | 0.003 | |
| Seizures, bicuculline for 20 min, range for three rat brain regions | 0.11–0.16§ | (Folbergrova et al., 1981) |
| Anoxia, mouse cerebral cortex, range for two assays in controls between 15 and 90 s after onset of anoxia | 0.8–1.4§ | (Gross and Ferrendelli, 1980) |
| Ischaemia, initial flux after decapitation, unanaesthetized adult mouse forebrain | 2.2 (peak rate = 3) | (Lowry et al., 1964) |
| Ischaemia, 20 s interval between decapitation and freezing mouse brain, range for four brain regions | 0.2–2.6§ | (Gatfield et al., 1966) |
| Ischaemia, 2 min before freezing sciatic nerve from anaesthetized rabbit | 0.17§ | (Stewart et al., 1965) |
| Aglycaemia, maximally stimulated rat or mouse optic nerve during ∼30 min aglycaemic perfusion in vitro | 0.02–0.03‡‡ | (Wender et al., 2000; Brown et al., 2003) |
| Aglycaemia, astrocyte culture, initial 10 min interval | 0.36§ | (Dringen et al., 1993) |
| Aglycaemia+10 mmol/l azide, initial 10 min interval | 0.50§ | |
| B. Glucose utilization rate | ||
| Resting rat brain tissue | ||
| Visual pathway | ||
| Optic nerve | 0.13§§ | Estimated rate |
| Optic chiasm | 0.16 | (Grunwald et al., 1988) |
| Superior colliculus | 0.69 | |
| Lateral geniculate | 0.76 | |
| Visual cortex | 0.93 | |
| Auditory pathway | ||
| Cochlear nucleus | 1.01 | |
| Superior olivary nucleus | 1.40 | |
| Lateral lemniscus | 0.94 | |
| Inferior colliculus | 1.69 | |
| Medial geniculate | 1.08 | |
| Auditory cortex | 1.36 | |
| Other regions of cerebral cortex | ||
| Sensorimotor cortex | 0.96 | |
| Parietal cortex | 0.87 | |
| Frontal cortex | 0.92 | |
| Piriform cortex | 1.09 | |
| Entorhinal cortex | 0.49 | |
| Cingulate cortex | 0.99 | |
| White matter | ||
| Corpus callosum | 0.25 | |
| Genu of corpus callosum | 0.20 | |
| Internal capsule | 0.22 | |
| Cerebellar white matter | 0.25 | |
| Ischaemia | ||
| Decapitation ischaemia, 20 s interval before freezing mouse brain, range for four brain regions | 1.15–3.18§ | (Gatfield et al., 1966) |
| Ischaemia, 2 min before freezing sciatic nerve from anaesthetized rabbit | 0.32§ | (Stewart et al., 1965) |
Rates determined by tracer [14C]glucose labelling, label clearance assays and metabolic modelling.
Glycogen turnover rate (i.e., synthesis rate = degradation rate when pool size constant) estimated during 4 h labelling with [1-13C]glucose to produce a constant plasma glucose level of 15 mmol/l and during label clearance for at least 3 h after cessation of label infusion. Net synthesis of glycogen during the hyperglycaemic infusion was anticipated by the authors, and the rate was probably overestimated.
Glycogen turnover rate calculated from rates of label incorporation and loss during and after programmed infusion of [1-13C]glucose in normal subjects with blood glucose level clamped at ∼6 mmol/l. Label washout rate after an 11 h [1-13]glucose infusion was ∼0.0005 μmol·g−1·min−1.
Glycogen or glucose utilization rates were calculated as net amount of glycogen (expressed in glucose units) or glucose consumed divided by the duration of the experimental interval. To compare results from different studies, values or rates reported in units ‘per mg protein’ were converted into wet weight, assuming 100 mg protein/g wet weight.
Range corresponds to the fall in glycogen level (1.47 μmol/g) from control to lethargy divided by either 20 or 35 min that corresponds to the beginning and end of the lethargy interval respectively (see Figure 1 and Table 3 in Ghajar et al., 1982).
Rate was calculated from glycogen consumed (i.e., the net increase in glycogen caused by inhibition of glycogen phosphorylase with CP-316,819 compared with saline-treated controls, ∼3 μmol/g) divided by the net increase in duration of neuronal activity prior to onset of isoelectric electroencephalogram during hypoglycaemia compared with hypoglycaemic saline-controls (∼90 min) (see Figure 3 and text, p. 48 in Suh et al., 2007). Glucose depletion relieves inhibition of phosphorylase by CP-316,819, and the additional glycogen can be consumed as needed.
Glycogen was first labelled by infusion of [1-13C]glucose for 4 h to clamp brain glucose at approximately 3 μmol/g. Glycogen degradation rate was calculated from label washout during a ∼2 h interval of insulin-induced hypoglycaemia that reduced brain glucose to approximately 0.1 μmol/g.
Label washout rate assayed during 2.5 h interval of euglycaemia (blood glucose, ∼5.2 mmol/l) or hypoglycaemia (blood glucose, ∼3.6 mmol/l) following an 11 h prelabelling period of infusion of [1-13C]glucose when both groups of subjects were euglycaemic (7.2 mmol/l). Turnover rate was calculated for euglycaemic control subjects.
Isolated mouse or rat optic nerves were first incubated with cerebrospinal fluid (aCSF) containing 10 mmol/l glucose for 1h, then perfused with artificial aCSF containing zero glucose while maximal compound action potentials (CAPs) were evoked every 30 s by electrical stimulation. Glycogen levels prior to stimulus onset were ∼5–10 pmol/μg optic nerve protein; assuming 100 mg protein/g optic nerve, initial glycogen levels were ∼0.5–1 μmol/g. Estimated glycogenolysis rates were calculated from net glycogen consumed during the interval between stimulus onset and CAP failure from data in Figure 3(B) and related text of Wender et al. (2000) and in Figure 2(D) of Brown et al. (2003).
Glucose utilization rate in optic nerve was not measured by Grünwald et al. (1988). Estimated rate was calculated from the relative rate of glucose utilization in optic nerve versus optic chiasm in urethane-anaesthetized monkeys as follows. Optic nerve/optic chiasm ≈0.82, estimated from Figure 4 of Sperber and Bill (1985) times the measured rate for optic chiasm (0.16, from Grünwald et al., 1988): 0.82×0.16 = 0.13.