Abstract
The aim of this study was to test the effects of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on insulin absorption from rat intestinal loops in situ, using a water-in-oil-in-water (W/O/W) multiple emulsion. The enhancement effect of these long-chain polyunsaturated fatty acids was compared with that of free fatty acids having a C18 alkyl chain. The emulsion (insulin dose, 50 units/kg) was administered directly into the colonic and rectal loops. Both EPA and DHA strongly enhanced insulin absorption and induced hypoglycemia after colonic and rectal dosing. Comparing the pharmacological availability, the order of effectiveness with respect to the enhanced absorption of insulin was DHA ≥ EPA > C18 unsaturated fatty acids ≫ C18 saturated fatty acid at both sites. DHA showed greater effects upon rectal dosing than upon colonic dosing. Histological studies revealed that the emulsion incorporating DHA did not induce gross morphological changes in the structure of the intestinal mucosa. Our results indicate that a W/O/W multiple emulsion incorporating DHA is a possible means of facilitating the intestinal absorption of insulin without inducing any serious damage to the epithelial cells.
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