ABSORPTION OF D-GLUCOSE IN THE RAT STUDIED USING IN-SITU INTESTINAL PERFUSION - A PERMEABILITY-INDEX APPROACH

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 (P-e) of [H-3]D-glucose and [C -14]antipyrine (an internal standard) in jejunum and ileum of four rat s was determined using an in situ rat intestinal perfusion technique. The permeability ratio of the test compound (D-glucose) to the interna l standard was defined as the permeability-index (P-i), which was math ematically independent of the length and surface area of the intestina l segment perfused. Using this approach, the transport of [H-3]D-gluco se in jejunum and ileum of eight animals was investigated at concentra tions ranging from 1 to 300 mM. The tissue/perfusate distribution of [ H-3]D-glucose and [C-14]antipyrine at steady state was also determined . Results. The variability (%CV) in P-i of D-glucose was only similar to 5%, compared with 23-36% in P-e values of D-glucose or antipyrine a lone. The permeability and tissue distribution of [C-14]antipyrine wer e unaffected by the presence of D-glucose. In contrast, the permeabili ty and tissue distribution of [H-3]D-glucose were concentration-depend ent in both jejunum and ileum. The transport of D-glucose was studied assuming that the transport was mediated by a carrier (with maximum fl ux, V-max and dissociation constant, K-m) as well as by non-saturable transport (P-d) The maximum transport capacity for D-glucose in jejunu m (0.522 mu mole/min/cm(2)) was twice that in ileum (0.199 mu mole/min / cm(2)), but the affinity (1/K-m) was less than half of that in ileum (1/ (48.2 mu mole/mL) vs. 1/(21.4 mu mole/mL)), rendering a similar a ctive transport efficiency (V-max/K-m) in these two regions. The non-s aturable permeability (P-d) in jejunum (44.6 x 10(-4) cm/min) was appr oximately twice that in ileum (20.4 x 10(-4) cm/min). Conclusions. The permeability-index approach yielded parameters with reduced variabili ty by eliminating potential imprecisions in length and surface area me asurements of the intestinal segment perfused. D-glucose was transport ed via carrier-mediated systems in both jejunum and ileum, with differ ent transport capacity and affinity in these two regions.