BIOCHEMICAL AND MORPHO-CYTOCHEMICAL EVIDENCE FOR THE INTESTINAL-ABSORPTION OF INSULIN IN CONTROL AND DIABETIC RATS - COMPARISON BETWEEN THEEFFECTIVENESS OF DUODENAL AND COLON MUCOSA

A combined biochemical and morpho-cytochemical investigation was carri ed out in order to assess insulin absorption by the duodenal and colon epithelium. Insulin was introduced in the lumen of the rat duodenum o r colon in combination with sodium cholate and aprotinin. Blood analys is made at several time points has demonstrated a rapid increase in ci rculating levels of insulin followed by significant and consistent dec reases in blood glucose. This indicates that biologically active insul in is absorbed by the intestinal mucosa and transferred to the circula tion. Because of the initial high blood glucose levels, the lowering o f the glycaemic values was more significant in diabetic animals. Also, levels of circulating insulin remained higher for longer time when th e administration was performed in the colon. The integrity of the inte stinal wall after insulin administration, evaluated morphologically, w as retained. Application of protein A-gold immunocyto-chemistry has es tablished the pathway for insulin absorption. In both duodenal and col on epithelial cells the labelling for insulin was detected in the endo somal compartment, in the Golgi apparatus and in association with the base-lateral plasma membrane interdigitations. Some labelling was also present in the interstitial space and in capillary endothelial plasma lemmal vesicles. Insulin introduced in the lumen of the rat duodenum a nd colon appears thus to be rapidly internalized by the epithelial cel ls and transferred through a transcytotic pathway to the interstitial space from which it reaches the blood circulation. This exogenous insu lin then induces significant decreases in plasma glucose levels which lasts for several hours. The results obtained support the possibility for the clinical development of an oral preparation of insulin.