250 Hypophysial Diabetes 



(attenuation of pancreatic diabetes by hypophysectomy, hypersensitivity to 

 insulin of hypophyscctoniized animals with or without pancreas, intense dia- 

 betogenic action of the anterior lobe in absence of the pancreas); (4) fasting 

 produces marked changes in hypophysectomized animals (rapid hypoglycemia 

 and death in animals with or without pancreas, great decrease in glycosuria 

 and in blood-sugar level of hypophysectomized-pancreatectomized dogs);^" 



(5) hypophysectomized dogs utilize food protein well but the endogenous ca- 

 tabolism is decreased during fasting or in pancreatic and phlorizin diabetes;^' ^^ 



(6) hypophysectomized-pancreatectomized dogs utilize glucose, excreting only 

 a part of the amount injected; hypoglycemia can appear during fasting, re- 

 covery following rapidly on administration of glucose;""'^ (7) hypophysectomy 

 decreases the ketonuria of pancreatic or phlorizin diabetes, as Rietti"" found 

 in 1931 ; (8) the removal of the posterior lobe* does not alleviate the symptoms 

 of pancreatic or phlorizin diabetes and does not increase the sensitivity to 

 insulin in the dog. 



In the following years we found^^"'" that: 1st, the diabetogenic action is 

 specific for the hypophysis, other organs being inactive; 2d, the anterior lobe 

 of vertebrates (fishes, batrachians, reptiles, birds, and mammals) is active when 

 injected into batrachians or mammals; 3d, removal of the hypophysis decreases 

 the intensity of pancreatic diabetes in mammals, reptiles, batrachians, and 

 fishes, and of phlorizin diabetes in mammals and batrachians. 



Oiu- work remained unnoticed from 1929 to 1931 and therefore we sent a 

 summary of it to two of the leading American medical journals. The paper 

 was not accepted by either of these journals but was finally published in 

 Endocrinology.^ After the appearance of this paper two workers in the Physi- 

 ological Institute of Chicago, Barnes and Regan,^ confirmed and extended our 

 experiments. Since 1934 Long and Lukens*" '^ in important papers confirmed 

 our results, using cats. 



In 1932 the diabetogenic action of the anterior hypophysis in mammals was 

 observed. The three papers which appeared were in chronological order: 1, 

 Evans, Meyer, Simpson and Reichert;"*^ 2, Bauman and Marine;'" 3, Houssay, 

 Biasotti and Rietti (with Di Benedetto).^^ Confirmatory experiments were 

 published in 1933 by Barnes and Regan," and E. I. Evans.^^ 



H. M. Evans and his co-workers"' *^ in their studies on the growth hormone 

 of the hypophysis injected anterior-lobe extracts free from gonadotrophic sub- 

 stances. They observed that a male dog after about eight months of continuous 

 injection "developed marked skin infections and abscesses, became emaciated 

 in spite of a large appetite, was easily exhausted, drank great amounts of water, 

 and excreted great amounts of urine. This led to investigation of the urine 

 of the injected male for the presence of sugar. It was present in large amounts. 

 Fasting blood sugar was also high (232 mg. per 100 cc). The animal was ob- 

 viously fail ing and injections were stopped to prevent its death. Four months 



* The alterations produced by dienceiDhalic lesions and total remo\al of the neinohy- 

 pophysis are still not clearly understood (see Davis and co-workers,^" and Houssay=»). 



