Gastrointestinal uptake and translocation of microparticles in the streptozotocin-diabetic rat

Uptake and translocation of particulates across the mucosal barrier of the gastrointestinal (GI) tract is now generally recognised but the effect of pathophysiologically induced changes on this process is less well established. This study evaluated the effect of diabetes mellitus on GI absorption of particles, comparing particle localisation and particle loading in different microanatomical sites of the primary organ (small intestine) and possible particle translocation pathways to selected secondary organs (mesenteric lymph nodes, liver, spleen) in normal and streptozotocin-induced diabetic animals. Fluorescent polystyrene latex particles (approximately 2 microns diameter) were fed orally to young adult Sprague-Dawley rats and quantitative bulk tissue and morphological techniques used to chart particle transit across the small intestine to secondary organs 0.5 h postadministration. In the normal animal, epifluorescence and confocal laser scanning microscopy provided confirmatory evidence for particle absorption within the primary organ and transport to other sites in the body. By contrast, in the diabetic animal, particle translocation and peripheral distribution were reduced with approximately 30% decrease in particle loading in the epithelial/nonepithelial tissue compartments. This could be a consequence of gastric retention and altered intestinal motility and permeability which are known to be associated with diabetes.