252 Hypophysial Diabetes 



createctomized and hypophysectomized toad, as shown by Campos, Curutchet 

 and Lanari" in 1933 and Foglia.=' By progressively reducing the amount of 

 liver left it was shown that when the loss was over 55 per cent the diabetogenic 

 action diminishes (Foglia'"). In dogs with full anterohypophysial diabetes, 

 hepatectomy produces a quick fall of the glucemia and within a few hours 

 they show serious hypoglycemic reactions, which disappear momentarily with 

 glucose. According to Soskin"^ the anterohypophysial diabetogenic action is 

 due to an overproduction of glucose in the liver. 



From 1934 to 1936 appeared the important works of Long and Lukens'"" 

 and in 1937 one by Long,'' studying the influence of hypophysectomy on pan- 

 creatic diabetes and the action of anterohypophysial extract in animals with 

 both operations. The above studies led them to investigate the influence of 

 adrenalectomy on pancreatic diabetes. In this field they did splendid work; 

 their last paper (Long, Katzin and Fry^) was in 1940. 



4. Misconceptioyis Prevailing in 19^6. During my trip to the United States 

 in 1936 I realized that two false notions were held: 1st, it was not possible to 

 observe the diabetogenic action in intact animals; 2d, the anterohypophysis 

 had no intrinsic action on the metabolism of the carbohydrates, its action 

 being exerted by way of the corticoadrenal hormones. 



Bennett, as well as Collip, and also Long and Lukens, had observed diageto- 

 genic action in animals without hypophysis and pancreas, but not in normals. 

 In reporting further work done in Evans's laboratory, RusselP in 1938 stated: 

 "In our own laboratory, in spite of initial successes, more extensive trials in 

 normal dogs and rabbits were unsuccessfid also, except in a few instances 

 which were considered doubtful because of attendant protein reactions in 

 the animals." 



In spite of this general incredulity, our Institute went on continuously ob- 

 taining and studying this diabetogenic action, which we have by now observed 

 in hundreds of dogs. The reason for our success was explained to all the above- 

 mentioned investigators and to Young (November, 1935) on the basis of the 

 following procedure used in preparing our extracts; immediately after the 

 slaughtering of the animals the hypophyses were placed in carbon-dioxide 

 snow and the dissection and subsequent preparation of the extracts was always 

 carried out near 0° C; the glands were kept frozen from then on; we realized 

 that at room temperature the glands and the extracts lose their action in a few 

 hours. Among all these investigators only Young followed our advice; that 

 is why he was able to accomplish the outstanding investigations well known 

 to all of us. 



When Young"' '^ in 1937 ^"^^ 193^ published his results the doubts vanished; 

 it explains why many believe he discovered the diabetogenic action of antero- 

 hypophysial extract, which really has been well known since 1930 and 1932. 



The idea that the diabetogenic action is mediated exclusively through the 

 adrenals comes from the work of Long. However, Long himself was always 

 rather cautious in his conclusions, and in the paper by Long, Katzin and Fry^" 



