Measurement of Size and Turnover Rate of Body Glucose Pool by the Isotope Dilution Method

TLDR

The study addresses errors arising from assuming instantaneous mixing in the body glucose pool during isotope dilution measurements. The authors aim to discuss the physiological significance of body glucose pool size and turnover rate measured by isotope dilution. They administered minute amounts of uniformly C‑14 labeled glucose intravenously to unanesthetized postabsorptive dogs, performed a priming dose followed by continuous infusion, measured plasma glucose specific activity over time, and calculated compartment sizes and mixing rates to assess errors in pool size and turnover estimates. They found that with an appropriate priming dose–infusion ratio, plasma glucose specific activity remained stable after 60 minutes, indicating two exchanging compartments, and that errors in pool size and turnover rate were below ±5% over a wide ratio range, obviating the need for preliminary experiments on each dog.

Abstract

Glucose uniformly labeled with C 14 was administered intravenously in minute amounts to unanesthetized dogs in the postabsorptive state as an initial dose followed by a continuous infusion. The C 14 content of the plasma glucose was determined at intervals. When the ratio of priming dose to infusion rate was suitable, the plasma glucose specific activity remained relatively constant during the 60–180-minute period of the infusion, whereas during the first 60 minutes it decreased in a manner indicating the presence of two compartments exchanging glucose with the plasma glucose compartment. For a typical experiment of this kind, the amounts of glucose in these compartments and the rates at which these bodies of glucose underwent mixing with the plasma glucose were calculated. It was then possible to determine the magnitude of the errors in body glucose pool size and inflow-outflow (i.e., turnover) rate which are made when measurements are carried out at various ratios of priming dose to infusion rate. These errors are incurred when the usual simplifying assumption is made that instantaneous mixing occurs throughout the body glucose pool. It was found that there is an extensive range of ratios of initial dose to infusion rate over which the errors are small enough (less than ± 5%) to be ignored; it is not necessary to carry out a preliminary experiment on each dog to establish a desirable ratio. Average values of body glucose pool size and glucose inflow-outflow rate obtained in 10 experiments with seven normal dogs are compared with values which have been reported by others. The physiological significance of these parameters measured by isotope dilution is discussed.