Intestinal glucose transport using perfused rat jejunum in vivo: model analysis and derivation of corrected kinetic constants.
1. The transport model that best describes intestinal glucose transport in vivo remains unsettled. Three models have been proposed: (1) a single carrier, (2) a single carrier plus passive diffusion, and (3) a two-carrier system. The objectives of the current studies were to define the transport model that best fits experimental data and to devise methods to obtain the kinetic constants, corrected for diffusion barrier resistance, with this model. 2. Intestinal glucose uptake was measured during perfusion of rat jejunum in vivo over a wide range of perfusate concentrations and diffusion barrier resistance was determined under identical experimental conditions. The data were fitted to the transport equations that describe the three models with appropriate diffusion barrier corrections, and the kinetic constants were derived by non-linear regression techniques. The fit of each model to the data was assessed using six statistical tests, five of which favoured a model described by a single carrier and passive diffusion. 3. The main conclusions of these studies are: (1) kinetic constants uncorrected for diffusion barrier resistance are seriously in error; (2) values for the derived kinetic constants are strongly dependent on the transport model selected for the data analysis which underscores the need for rigorous model analysis; (3) corrected kinetic constants may be obtained by either non-linear regression or by a simpler graphical analysis once the correct transport model has been selected and diffusion barrier resistance determined; (4) only corrected kinetic constants should be used for inter-species comparisons or to study the effect of specific interventions on intestinal glucose transport.
Meddings
J B
JB
Department of Internal Medicine, University of Texas Health Science Center, Southwestern Medical School, Dallas 75235-9030.
Westergaard
H
H
D000818:Animals; D001692:Biological Transport; D004058:Diffusion; D005260:Female; D005947:Glucose / Q000493:pharmacokinetics*; D007408:Intestinal Absorption; D007583:Jejunum / Q000378:metabolism*; D007700:Kinetics; D008433:Mathematics; D008954:Models, Biological; D010477:Perfusion; D051381:Rats; D011919:Rats, Inbred Strains
D005947:Glucose