Sensitivity of myocardial fluorodeoxyglucose lumped constant to glucose and insulin

C. K. Ng, J. E. Holden, T. R. DeGrado, D. M. Raffel, M. L. Kornguth, S. J. Gatley

Research output: Contribution to journalArticle

58 Scopus citations

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 coditions 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.

Original languageEnglish (US)
Pages (from-to)H593-H603
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume260
Issue number2 29-2
DOIs
StatePublished - 1991

Keywords

  • Glycolysis
  • High external work load
  • Isolated rat heart

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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