Estimating glucose metabolism using glucose analogs and two tracer kinetic models in isolated rabbit heart

Abstract

The purpose of this investigation was to 1) evaluate the relative accuracy of the Sokoloff and Patlak tracer kinetic models in estimating glucose metabolic rate (GMR) in the presence and absence of insulin; 2) evaluate the effect of nutritional state on the lumped constant (LC); and 3) compare the kinetics of 2-fluoro-2-deoxy-d-[14C]glucose (FDG) and 2-deoxy-d-[3H]glucose (DG) membrane transport and phosphorylation. The experimental preparation was the isolated, red blood cell-albumin-perfused rabbit heart. Our results showed that both tracer kinetic models provided GMR estimates that correlated well with the Fick method (for FDG, R = 0.84 and 0.91 for the Sokoloff and Patlak models, respectively); nutritional state did not affect the LC; and FDG and DG have different transport and/or phosphorylation parameters. We also observed that 1) the addition of a fourth compartment to the Sokoloff model reduced the mean squared error between measured and modeled data by a factor of 7.4; 2) a longer time (21.8 min) was required to obtain a linear phase of the Patlak plot than is allowed in clinical studies; and 3) accurate GMR estimates were obtained only by using different LCs reflecting insulin’s presence or absence. Our results indicate potential sources of error in the use of FDG and positron emission tomography to quantify GMR in patients.

Role of glycolysis in the energy production for the non-mechanical myocardial work in isolated pig hearts

“…Indeed, some studies conducted on rabbits 30 and rats [31][32][33] have shown a difference between the uptake of 18 FDG and the glucose molecule, with variations in insulin concentration 29 , the presence of competitive substrates 29 , and the ischaemia-reperfusion sequence [32][33][34] . These differences of uptake between the tracer and the substrate molecule would be due to the variations of the lumped constant that would not always be equal to 0.67 33 .…”

Kinetic modeling of [18F]FDG in skeletal muscle by PET: a four-compartment five-rate-constant model

“…The use of compartmental models to describe [ 18 F]FDG kinetics in human skeletal muscle has recently seen important contributions (14,15,19,26,34). Common to all these reports is the tacit assumption that the 3K and 4K models, which were originally proposed to describe [ 18 F]FDG kinetics in the brain (24,31), also provide the appropriate compartmental structure for studying human skeletal muscle.…”

“…Recent reports indicate that the lumped constant is relatively insensitive to insulin (16,23,33), but glucose and [ 18 F]FDG individual unit processes exhibit different affinity. However, [ 18 F]FDG has proven to be a sensitive probe for assessing the individual steps of metabolism in human skeletal muscle in various physiopathological states (14,15,19,26,30,34).…”

Dissociation of glucose tracer uptake and glucose transporter distribution in the regionally ischaemic isolated rat heart: application of a new autoradiographic technique

“…In myocardial tissue, the dephosphorylation rate is negligible [26], and thus the accumulation of glucose analogues in the myocyte can essentially be viewed as a combination of transport and phosphorylation. The rate of transport is governed by the number of transporters present at the sarcolemma and the affinity of the transporters for their respective substrates.…”