title: Sensitivity of myocardial fluorodeoxyglucose lumped constant to glucose and insulin.
abstract: The lumped constant (LC) that relates the steady-state phosphorylation rate of 2-[18F]-fluoro-2-deoxy-D-glucose (2-FDG) to that of glucose was determined in an isolated working rat heart model by direct assay of phosphorylation product formation. Five conditions were tested: 5 and 30 mM glucose without insulin, and 2, 3.5, and 5 mM glucose + 10 mU/ml insulin, all at high external work load. Hearts were continuously perfused with 2-FDG and tritiated glucose without recirculation. The steady-state production of tritiated water was used to monitor the glucose phosphorylation rate. Perfused hearts were freeze-clamped and extracted in perchloric acid, and 2-FDG-6-phosphate was separated from 2-FDG with a formate column. The accumulation of 2-FDG phosphorylation products in tissue was also determined from the slopes of the total tissue radioactivity time courses measured by external gamma-ray detection. Without insulin, the LC value decreased 18% as perfusate glucose concentration was increased sixfold (0.94 +/- 0.06 at 5 mM vs. 0.77 +/- 0.17 at 30 mM). With insulin, the LC rose from 0.33 +/- 0.03 at 5 mM to 1.19 +/- 0.05 at 2 mM glucose concentration. The trends can be interpreted in terms of the concept of control strength; the LC value rises as glycolysis becomes rate limited by transport into cells. This potential variability of the LC must be addressed in the quantitative interpretation of myocardial deoxyglucose studies.
authors.affiliation: Department of Medical Physics, University of Wisconsin, Madison 53706.
authors.forename: C K
authors.initials: CK
authors.lastname: Ng
authors.forename: J E
authors.initials: JE
authors.lastname: Holden
authors.forename: T R
authors.initials: TR
authors.lastname: DeGrado
authors.forename: D M
authors.initials: DM
authors.lastname: Raffel
authors.forename: M L
authors.initials: ML
authors.lastname: Kornguth
authors.forename: S J
authors.initials: SJ
authors.lastname: Gatley
mesh_terms: D000818:Animals; D003326:Coronary Circulation; D003847:Deoxyglucose / Q000031:analogs & derivatives* / Q000378:metabolism; D019788:Fluorodeoxyglucose F18; D005947:Glucose / Q000493:pharmacokinetics / Q000494:pharmacology*; D066298:In Vitro Techniques; D007328:Insulin / Q000494:pharmacology*; D009206:Myocardium / Q000378:metabolism*; D009994:Osmolar Concentration; D010477:Perfusion; D051381:Rats; D011919:Rats, Inbred Strains; D014018:Tissue Distribution
chemical_list: D007328:Insulin; D019788:Fluorodeoxyglucose F18; D003847:Deoxyglucose; D005947:Glucose