Experimental validation of measurements of glucose turnover in nonsteady state

The aim of the present experiments is to validate, in conscious dogs, the tracer infusion methods of measuring nonsteady turnover rates. This was done in nine experiments performed in four normal dogs by infusing isotopically labeled glucose (2-3H, 6-3H, 1-14C) and monitoring the concentrations of both the labeled and unlabeled substances. The validation is based on the observation that a high exogenous infusion of glucose will suppress endogenous glucose production and become the sole source of glucose in the body. By infusing glucose at a high, time-varying rate, calculating its rate of appearance, (Ra) and comparing it to the infused rate, the method can be verified. The calculations were based on: a) a single-compartment model with a modified volume of distribution; b) a two-compartment model; and c) a generalized dispersion model. The absolute values of the areas of the deviations of the calculated from the infused curves were found to be, respectively, 9.5, 8.4, and 7.8 percent of the total area under the infused curve. It was concluded that the tracer infusion method can reliably measure Ra of glucose when it is changing rapidly, and the system is out of steady state.