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

The lumped constant (LC) is used to convert the clearance rate of 2-deoxy-D-glucose (2-DG(CR)) to that of glucose (Glc(CR)). 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-C-14] glucose (2-DG) in 18 normal male subjects (age, 29 +/- 2 yr; body mass index, 24.8 +/- 0.8 kg/m(2)) after an overnight fast and during physiological (1 mU . kg(-1) . min(-1) insulin infusion for 180 min) and supraphysiological (5 mU . kg(-1) . min(-1) insulin 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-H-3] glucose, 2-[1-C-14] DG, and [C-12] mannitol (Man) were injected as a bolus into the brachial artery. The concentrations of [3-H-3] glucose and 2-[1-C-14] DG (dpm/ml plasma) and of Man (mu mol/l) were determined in 50 blood samples withdrawn from the ipsilateral deep forearm vein over 15 min after the bolus injection.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 Glc(CR) and 2-DG(CR). 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(-1) insulin 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.