Direct measurement of the lumped constant for 2-deoxy-[1-14C]glucose in vivo in human skeletal muscle

Abstract

The lumped constant (LC) is used to convert the clearance rate of 2-deoxy-d-glucose (2-DGcr) to that of glucose (Glccr). There are currently no data to validate the widely used assumption of an LC of 1.0 for human skeletal muscle. We determined the LC for 2-deoxy-[1-14C]glucose (2-DG) in 18 normal male subjects (age, 29 ± 2 yr; body mass index, 24.8 ± 0.8 kg/m2) after an overnight fast and during physiological (1 mU · kg−1· min−1insulin infusion for 180 min) and supraphysiological (5 mU · kg−1· min−1insulin infusion for 180 min) hyperinsulinemic conditions. Normoglycemia was maintained with the euglycemic clamp technique. The LC was measured directly with the use of a novel triple tracer-based method. [3-3H]glucose, 2-[1-14C]DG, and [12C]mannitol (Man) were injected as a bolus into the brachial artery. The concentrations of [3-3H]glucose and 2-[1-14C]DG (dpm/ml plasma) and of Man (μmol/l) were determined in 50 blood samples withdrawn from the ipsilateral deep forearm vein over 15 min after the bolus injection. The LC was calculated by a formula involving blood flow calculated from Man and the Glccrand 2-DGcr. The LC averaged 1.26 ± 0.08 (range 1.06–1.43), 1.15 ± 0.05 (0.99–1.39), and 1.18 ± 0.05 (0.97–1.37) under fasting conditions and during the 1 and 5 mU · kg−1· min−1insulin infusions (not significant between the different insulin concentrations, mean LC = 1.2, P < 0.01 vs. 1.0). We conclude that, in normal subjects, the LC for 2-DG in human skeletal muscle is constant over a wide range of insulin concentrations and averages 1.2.