Intestinal glucose transport using perfused rat jejunum in vivo: model analysis and derivation of corrected kinetic constants

Abstract

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.

Kinetics and mechanisms of glucose absorption in the rat small intestine under physiological conditions

“…In accordance with the classic view, glucose is transported across the brush border membrane by Na + /glucose co-transporter SGLT1, while the facilitated diffusion mediated by GLUT2 provides the output of glucose from enterocytes across the basolateral membrane into the extracellular space [1][2][3][4][5][6][7].…”

“…The results of numerous experiments in vivo have also revealed the existence of unsaturated ("diffusion") component of glucose absorption, which may exceed greatly the secondary active transport through SGLT1 at high substrate concentrations [6,8,9].…”

“…2) Absorption of glucose (both free, and released from maltose hydrolysis) is mainly determined by permeability of the apical membrane of the enterocytes and can be described by the well-known equation [4,6]:…”

“…We have used two approximations of the complex surface of the intestinal epithelium (Figure 1): a smooth surface with adjacent diffusion layer [4,6,7,11] (Figure 1(a)), and a folded surface with a diffusion layer between the folds, and partly over them (Figure 1(b)). …”

“…The experimental data were analyzed on the mathematical model with commonly used approximation of the intestinal epithelium in the form of a smooth surface with adjacent diffusion layer [4,6,7,11], and on the original model, which took into account geometric specificities of the intestinal surface [19].…”