title: A new Michaelis-Menten-based kinetic model for transport and phosphorylation of glucose and its analogs in skeletal muscle.
abstract: OBJECTIVE
  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 VH 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 VH. 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.
authors.affiliation: Department of Biomedical Engineering, Case Western Reserve University, Cleveland, Ohio 44106, USA.
authors.forename: Hsuan-Ming
authors.initials: HM
authors.lastname: Huang
authors.forename: Faramarz
authors.initials: F
authors.lastname: Ismail-Beigi
authors.forename: Raymond F
authors.initials: RF
authors.lastname: Muzic
mesh_terms: D000818:Animals; D001693:Biological Transport, Active; D001786:Blood Glucose / Q000378:metabolism; D019788:Fluorodeoxyglucose F18 / Q000493:pharmacokinetics; D005947:Glucose / Q000031:analogs & derivatives / Q000378:metabolism*; D015309:Glucose Clamp Technique; D006946:Hyperinsulinism / Q000378:metabolism; D008954:Models, Biological; D018482:Muscle, Skeletal / Q000000981:diagnostic imaging* / Q000378:metabolism*; D010766:Phosphorylation; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D051381:Rats
chemical_list: D001786:Blood Glucose; D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18; D005947:Glucose