Transport kinetics of D-glucose in human small intestinal mucosa: rate constants in histologically normal and abnormal mucosal biopsies

Abstract

Using D-glucose as the probe molecule, we analysed conditions which must be fulfilled in mucosal biopsy studies before the kinetic nature of the transport process can be established. Mucosal biopsies were obtained from the region of the ligament of Treitz from four healthy volunteers and from 47 patients: 29 of the 47 had histologically normal mucosa; seven had mild abnormalities; and 11 had moderate or severe ("flat") abnormalities in villus architecture. The rate of uptake of 40 mM glucose was constant only between 4 and 10 min, extrapolating through zero uptake at zero time with a constant adherent mucosal fluid volume. Incubation for shorter or longer periods was associated with over- or underestimation of the rate of uptake. Failure to use a nonabsorbable marker was also associated with overestimation of the rate of uptake. When biopsies were incubated for 6 min, a curvilinear relationship was observed between uptake rate and concentration. In biopsies with moderate and severe abnormalities, there was a marked reduction in the magnitude of the maximal transport rate and the apparent passive permeability coefficient, with little change in the magnitude of the apparent affinity constant. When human mucosal biopsies are used to study nutrient absorption, certain criteria must be fulfilled to establish valid rate constants and to make comparisons between normal and abnormal mucosa.