Determination of local brain glucose level with [14C]methylglucose: effects of glucose supply and demand

Abstract

Methylglucose can be used to assay brain glucose levels because the equilibrium brain-to-plasma distribution ratio for methylglucose ([Formula: see text]/[Formula: see text]) is quantitatively related to brain (Ce) and plasma (Cp) glucose contents. The relationship between Ce and[Formula: see text]/[Formula: see text]predicted by Michaelis-Menten kinetics has been experimentally confirmed when glucose utilization rate (CMRGlc) is maintained at normal, resting levels and Cp is varied in conscious rats. Theoretically, however, Ce and[Formula: see text]/[Formula: see text]should change when CMRGlc is altered and Cp is held constant; their relationship in such conditions was, therefore, examined experimentally. Drugs were applied topically to brains of conscious rats with fixed levels of Cp to produce focal alterations in CMRGlc, and Ce and[Formula: see text]/[Formula: see text]were measured. Plots of Ce as a function of[Formula: see text]/[Formula: see text]for each Cp produced straight lines; their slopes decreased as Cp increased. The results confirm that a single theoretical framework describes the relationship between Ce and[Formula: see text]/[Formula: see text]as either glucose supply or demand is altered over a wide range; they also validate the use of methylglucose to estimate local Ce under abnormal conditions.