ENHANCED COLONIC AND RECTAL ABSORPTION OF INSULIN USING A MULTIPLE EMULSION CONTAINING EICOSAPENTAENOIC ACID AND DOCOSAHEXAENOIC ACID

The aim of this study was to test the effects of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on insulin absorption from rat i ntestinal loops in situ, using a water-in-oil-in-water (W/O/W) multipl e emulsion. The enhancement effect of these long-chain polyunsaturated fatty acids was compared with that of free fatty acids having a C18 a lkyl 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 wa s DHA greater than or equal to EPA > C18 unsaturated fatty acids much greater than C18 saturated fatty acid at both sites. DHA showed greate r effects upon rectal dosing than upon colonic dosing. Histological st udies revealed that the emulsion incorporating DHA did not induce gros s morphological changes in the structure of the intestinal mucose. 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.