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

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