Observations on Various Insulin Mixtures Administered Per Os

Abstract

At the time of publication of Stephan's paper 1 on the use of “cholosulin”, a desoxycholic acid-insulin mixture, we were engaged in the preparation and study of a similar compound based on identical theoretical considerations. Mixtures of desoxycholic acid and insulin were prepared and administered by stomach tube to fasting rabbits, the experiments controlled by subcutaneous injection. The results in 4 experiments with 4 rabbits each, were inconclusive. The blood sugar curves closely paralleled the controls. The recent reports of Bronkhorst, Freud and Laquer, 2 and Wahncau and Bertram, 3 seem to show some slight effect on carbohydrate metabolism by this compound, but they ascribe it to the bile acid and not the insulin in the mixture. The clinical use of Stephan's preparation by Umber and Rosenberg, 4 and others has not proven successful. Our mixture also had no effect on human diabetes.

Another line of approach to the problem of a practical and successful method of administering insulin by mouth suggested itself. In order to attempt the prevention of digestion of insulin in the gastro-intestinal tract, a preparation from the juice of ground and pressed Ascaris lumbricoides of the pig, yielding a potent, assayable anti-protease fraction, was made by the method of Weinland. 5 This substance, a fluffy, white, sticky powder, was assayed in potency by titrating it against active peptic and pancreatic proteases. In definite quantities it prevented the digestion of egg-white and casein. The action is inhibitory and not permanent, lasting about 24 hours.

When a known concentration of this anti-protease was added to mixtures of commercial insulin plus either peptic or tryptic proteases, the potency of the insulin as tested by subcutaneous injection into 8 fasting rabbits, was unimpaired. Typical hypoglycemic reactions resulted.