A glycogen phosphorylase inhibitor selectively enhances local rates of glucose utilization in brain during sensory stimulation of conscious rats: implications for glycogen turnover


Address correspondence and reprint requests to Gerald A. Dienel, Department of Neurology, Shorey Building, Room 715, Slot 830, University of Arkansas for Medical Sciences, 4301W. Markham Street, Little Rock, AR 72205, USA. E-mail: gadienel@uams.edu


Glycogen is degraded during brain activation but its role and contribution to functional energetics in normal activated brain have not been established. In the present study, glycogen utilization in brain of normal conscious rats during sensory stimulation was assessed by three approaches, change in concentration, release of 14C from pre-labeled glycogen and compensatory increase in utilization of blood glucose (CMRglc) evoked by treatment with a glycogen phosphorylase inhibitor. Glycogen level fell in cortex, 14C release increased in three structures and inhibitor treatment caused regionally selective compensatory increases in CMRglc over and above the activation-induced rise in vehicle-treated rats. The compensatory rise in CMRglc was highest in sensory-parietal cortex where it corresponded to about half of the stimulus-induced rise in CMRglcf in vehicle-treated rats; this response did not correlate with metabolic rate, stimulus-induced rise in CMRglc or sequential station in sensory pathway. Thus, glycogen is an active fuel for specific structures in normal activated brain, not simply an emergency fuel depot and flux-generated pyruvate greatly exceeded net accumulation of lactate or net consumption of glycogen during activation. The metabolic fate of glycogen is unknown, but adding glycogen to the fuel consumed during activation would contribute to a fall in CMRO2/CMRglc ratio.