Measurement of Insulin Action. ∗

Abstract

The insulin required to maintain a normal blood sugar level in depancreatized dogs has been studied by Holm 1 and in the laboratories of Houssay 2 and Soskin. 3 , 4 Holm and Houssay found that 0.01 unit insulin per kilogram of body weight per hour was necessary. Soskin found values as low as 1-175th unit insulin per kg. per hour in dogs under pento-barbital sodium (Abbott).

We have determined the insulin requirement in dogs of different sizes which have completely recovered from the pancreatectomy. These dogs were maintained at a constant weight on a measured balanced diet and sufficient insulin to keep the urine nearly sugar-free. They received no food or insulin for 24 hours prior to a determination. No anesthetic was used. The initial high blood sugar was lowered to about 100 mg.% by an intravenous injection of 2-6 units of insulin, depending upon the size of the animal. A continuous or hourly intravenous injection of a weak solution of insulin in physiological saline was started about 4-6 hours following the initial injection. An amount is given which will keep the blood sugar at about 120 mg. %. Table I summarizes the results on 4 different animals.

Determinations of the insulin-glucose ratio were made. In one experiment the basal insulin requirement was increased from 0.21 unit insulin per hour to 0.41 unit and a continuous intravenous injection of 5% glucose was given. After 5 hours it was possible to inject 3.48 gm. of glucose per hour with the blood sugar constant at 125 mg. %. On the basis of the added insulin, the insulin-glucose ratio was therefore 1 unit to 17.4 gm. In another experiment 1 unit additional insulin per hour was added to the basal rate of 0.09 units insulin per hour, making a total of 1.09 units of insulin per hour. Eleven hours after starting the injection of glucose, 9.0 p. per hour were being given with a blood sugar of 116 mg. %. More experiments of this nature are in progress with varying amounts of insulin.