A new Michaelis-Menten-based kinetic model for transport and phosphorylation of glucose and its analogs in skeletal muscle

Purpose: A new model is introduced that individually resolves the delivery, transport, and phosphorylation steps of metabolism of glucose and its analogs in skeletal muscle by interpreting dynamic positron emission tomography (PET) data.Methods: The model uniquely utilizes information obtained from the competition between glucose and its radiolabeled analogs. Importantly, the model avoids use of a lumped constant which may depend on physiological state. Four basic physiologic quantities constitute our model parameters, including the fraction of total tissue space occupied by interstitial space (f_IS), a flow-extraction product and interstitial (IS_g) and intracellular (IC_g) glucose concentrations. Using the values of these parameters, cellular influx (CI) and efflux (CE) of glucose, glucose phosphorylation rate (PR), and maximal transport (V^G) and phosphorylation capacities (V^H) can all be determined. Herein, the theoretical derivation of our model is addressed and characterizes its properties via simulation. Specifically, the model performance is evaluated by simulation of basal and euglycemic hyperinsulinemic (EH) conditions.Results: In fitting the model-generated, synthetic data (including noise), mean estimates of all but IC_g of the parameter values are within 5% of their values for both conditions. In addition, mean errors of CI, PR, and V^G are less than 5% whereas those of V^H and CE are not.Conclusions: It is concluded that under the conditions tested, the novel model can provide accurate parameter estimates and physiological quantities, except IC_g and two quantities that are dependent on IC_g, namely CE and V^H. However, the ability to estimate IC_g seems to improve with increases in intracellular glucose concentrations as evidenced by comparing IC_g estimates under basal vs EH conditions.