Author(s): Ziv E, Bendayan M
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Abstract Transport of intact peptides and proteins from the intestinal lumen into the blood is a unique phenomenon, which differs from the regular process of food digestion and absorption. Intestinal absorption of minute amounts of proteins is, however, being considered as a normal physiological process. It is thus important to define and understand the routes for protein transfer from the intestinal lumen to the blood and the mechanisms by which the macromolecules overcome the sieving barrier of the intestinal wall. The study on insulin has demonstrated that, upon proper introduction into the intestinal lumen, insulin is absorbed by the epithelial cells and transferred to the circulation. The peptides absorbed and transferred to the blood retained their biological activity and induced significant lowering of blood glucose levels. The efficiency of the absorption does not differ among the ileum, duodenum, and colon. Morphological examination demonstrated no alteration of the structural integrity of the epithelia, the enterocytes stay intact with well-developed microvilli, and the cells remain joined by tightly closed junctions. Application of immunocytochemistry on thin tissue sections revealed insulin antigenic sites at different locations depending on the time point. Insulin detected in the lumen of the intestinal tract is absorbed through the endosomal compartment of the epithelial cells rather than passing between cells. Internalization occurs through invaginations of the luminal plasma membrane and vesicular structures of the endosomal compartment. In 5-10 minutes, insulin is transferred to the basolateral membrane and released into the interstitial space to reach the circulation. Definition of the transcytotic pathway will contribute to a better understanding of drug delivery for potential therapeutic applications. Copyright 2000 Wiley-Liss, Inc.
This article was published in Microsc Res Tech
and referenced in Journal of Bioequivalence & Bioavailability