THE INCREASED DURATION OF INSULIN ACTION BY THE USE OF PROTAMINE ZINC INSULIN IN PELLET FORM1

BEST (1) has reviewed the numerous attempts to prolong the action of insulin. Many recent experiments have shown the increased effectiveness of compressed pellets of estrone, testosterone propionate and desoxycorticosterone implanted subcutaneously (2, 3). We are reporting experiments on the effect of compressed subcutaneous pellets of crystalline Zn insulin3 and mixtures of crystalline Zn insulin with protamine, on the blood sugar concentration of dogs. Adult dogs were depancreatized under nembutal anesthesia, and stabilized on a diet of lean meat 250 gm., cane sugar 25 gm., and pancreas 50 gm., given at 9 A.M. and 4 P.M. daily. The dogs received 10 u of insulin daily, except on the day before each experiment. Pellets were made of crystalline Zn insulin and carefully ground mixtures of Zn insulin and protamine, in an apparatus made for this purpose. The apparatus has two steel plates (fig. 1) with opposing surfaces that are machine ground. These can be fastened firmly together.