Enteral Absorption of Insulin

Abstract

Previous studies dealing with the enteral absorption of insulin have demonstrated the marked impermeability of the intestinal mucosa to this hormone. 1 It was considered of practical and theoretical interest to attempt to increase this degree of permeability by means of concomitantly administered drugs.

Normal dogs were prepared with Thierry loops about 12 cm. in length taken from about 50-60 cm. above the terminal ileum. Balloon and catheter arrangements similar to those described by Johnston 2 were used to insure retention of the introduced insulin mixture. This mixture was made up of Insulin-Lilly U-40 or U-80 and diluted with saline to 2 1/2 or 3 1/2 cc. before introduction. Blood samples were taken from the ear and sugar determined by the micro-method of Folin and Malmros. 3 (This method in our hands gives high absolute figures in the hypoglycemic range.) The dogs were ordinarily starved for 40 hours previous to the experiment. For purposes of brevity, the following hypoglycemic reaction, taken from the protocols is referred to as “typical hypoglycemia”. Normal blood sugar 102 mg. %; 1 1/2 hr. later 106. Insulin introduced. After 15 min., 94; 50 min., 65; 1 1/2 hr., 65; 2 hr., 58; 2 1/3 hr., 62;3 hr., 79 mg. %.

With insulin in saline alone, about 35 units per kg. body weight represents the minimal dosage producing typical hypoglycemia.

One trial with an addition of hexyl resorcinol and toluene failed to show favorable influence on absorption. One trial with 0.3% saponin and 5% lactic acid produced typical hypoglycemia with 1/2 the usual amount of insulin.∗

Several trials of insulin in a 20% alcohol solution produced typical hypoglycemia with dosages 1/2 to 1/3 those producing the same effect in saline alone.