Absorption of D-glucose in the rat studied using in situ intestinal perfusion: a permeability-index approach

Abstract

Purpose: A permeability-index approach was developed and used to study the transport of D-glucose in the jejunum and ileum of rats.

Methods: The effective permeability coefficient (Pe) of [3H]D-glucose and [14C]antipyrine (an internal standard) in jejunum and ileum of four rats was determined using an in situ rat intestinal perfusion technique. The permeability ratio of the test compound (D-glucose) to the internal standard was defined as the permeability-index (P(i)), which was mathematically independent of the length and surface area of the intestinal segment perfused. Using this approach, the transport of [3H]D-glucose in jejunum and ileum of eight animals was investigated at concentrations ranging from 1 to 300 mM. The tissue/perfusate distribution of [3H]D-glucose and [14C]antipyrine at steady state was also determined.

Results: The variability (%CV) in P(i) of D-glucose was only approximately 5%, compared with 23-36% in Pe values of D-glucose or antipyrine alone. The permeability and tissue distribution of [14C]antipyrine were unaffected by the presence of D-glucose. In contrast, the permeability and tissue distribution of [3H]D-glucose were concentration-dependent in both jejunum and ileum. The transport of D-glucose was studied assuming that the transport was mediated by a carrier (with maximum flux, Vmax and dissociation constant, Km) as well as by non-saturable transport (Pd). The maximum transport capacity for D-glucose in jejunum (0.522 mumole/min/cm2) was twice that in ileum (0.199 mumole/min/cm2), but the affinity (1/Km) was less than half of that in ileum (1/(48.2 mumole/mL) vs. 1/(21.4 mumole/mL)), rendering a similar active transport efficiency (Vmax/Km) in these two regions. The non-saturable permeability (Pd) in jejunum (44.6 x 10(-4) cm/min) was approximately twice that in ileum (20.4 x 10(-4) cm/min).

Conclusions: The permeability-index approach yielded parameters with reduced variability by eliminating potential imprecisions in length and surface area measurements of the intestinal segments perfused. D-glucose was transported via carrier-mediated systems in both jejunum and ileum, with different transport capacity and affinity in these two regions.