Direct Chemical Measurement of the λ of the Lumped Constant of the [14C]Deoxyglucose Method in Rat Brain: Effects of Arterial Plasma Glucose Level on the Distribution Spaces of [14C]Deoxyglucose and Glucose and on λ

Abstract

The lumped constant in the operational equation of the 2-[¹⁴C]deoxyglucose (DG) method contains the factor λ that represents the ratio of the steady-state tissue distribution spaces for [¹⁴C]DG and glucose. The lumped constant has been shown to vary with arterial plasma glucose concentration. Predictions based mainly on theoretical grounds have suggested that disproportionate changes in the distribution spaces for [¹⁴C]DG and glucose and in the value of λ are responsible for these variations in the lumped constant. The influence of arterial plasma glucose concentration on the distribution spaces for DG and glucose and on λ were, therefore, determined in the present studies by direct chemical measurements. The brain was maintained in steady states of delivery and metabolism of DG and glucose by programmed intravenous infusions of both hexoses designed to produce and maintain constant arterial concentrations. Hexose concentrations were assayed in acid extracts of arterial plasma and freeze-blown brain. Graded hyperglycemia up to 28 m M produced progressive decreases in the distribution spaces of both hexoses from their normoglycemic values (e.g., ∼ – 20% for glucose and – 50% for DG at 28 m M). In contrast, graded hypoglycemia progressively reduced the distribution space for glucose and increased the space for [¹⁴C]DG. The values for λ were comparatively stable in normoglycemic and hyperglycemic conditions but rose sharply (e.g., as much as 9–10-fold at 2 m M) in severe hypoglycemia.