title: Direct measurement of the lumped constant for 2-deoxy-[1-(14)C]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-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of [3-(3)H]glucose and 2-[1-(14)C]DG (dpm/ml plasma) and of Man (micromol/l) were determined in 50 blood samples withdrawn from the ipsilateral deep forearm vein over 15 min after the bolus injection.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.
authors.affiliation: Division of Diabetology, Department of Medicine, University of Helsinki, FIN-00029 HUCH, Helsinki, Finland.
authors.forename: T
authors.initials: T
authors.lastname: Utriainen
authors.forename: S
authors.initials: S
authors.lastname: Lovisatti
authors.forename: S
authors.initials: S
authors.lastname: Mäkimattila
authors.forename: A
authors.initials: A
authors.lastname: Bertoldo
authors.forename: S
authors.initials: S
authors.lastname: Weintraub
authors.forename: R
authors.initials: R
authors.lastname: DeFronzo
authors.forename: C
authors.initials: C
authors.lastname: Cobelli
authors.forename: H
authors.initials: H
authors.lastname: Yki-Järvinen
mesh_terms: 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
chemical_list: D001786:Blood Glucose; D002250:Carbon Radioisotopes; D007328:Insulin; D008353:Mannitol; D003847:Deoxyglucose; D005947:Glucose