Direct measurement of the lumped constant for 2-deoxy-[1-(14)C]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-(14)C]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 x kg(-1) x min(-1) insulin infusion for 180 min) and supraphysiological (5 mU x kg(-1) x 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-(3)H]glucose, 2-[1-(14)C]DG, and [(12)C]mannitol (Man) were injected as a bolus into the brachial artery. The concentrations of [3-(3)H]glucose and 2-[1-(14)C]DG (dpm/ml plasma) and of Man (micromol/l) were determined in 50 blood samples withdrawn from the ipsilateral deep forearm vein over 15 min after the bolus injection.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 x 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.
Utriainen
T
T
Division of Diabetology, Department of Medicine, University of Helsinki, FIN-00029 HUCH, Helsinki, Finland.
Lovisatti
S
S
Mäkimattila
S
S
Bertoldo
A
A
Weintraub
S
S
DeFronzo
R
R
Cobelli
C
C
Yki-Järvinen
H
H
D000328:Adult; D001786:Blood Glucose / Q000032:analysis; D002250:Carbon Radioisotopes; D003847:Deoxyglucose / Q000493:pharmacokinetics*; D004435:Eating / Q000502:physiology; D005542:Forearm; D005947:Glucose / Q000493:pharmacokinetics; D015309:Glucose Clamp Technique; D006801:Humans; D007328:Insulin / Q000097:blood; D008297:Male; D008353:Mannitol / Q000097:blood; D008954:Models, Biological; D018482:Muscle, Skeletal / Q000098:blood supply / Q000378:metabolism*; D009994:Osmolar Concentration; D012016:Reference Values; D012039:Regional Blood Flow
D001786:Blood Glucose; D002250:Carbon Radioisotopes; D007328:Insulin; D008353:Mannitol; D003847:Deoxyglucose; D005947:Glucose