B. A. Houssay 249 



In 1927 Davidoff and Gushing'" observed that insulin acts on the diabetes oi 

 acromegaly but that larger amounts are needed to obtain normal blood sugar 

 than in other types of diabetes.* They attributed the insulin resistance to a 

 pituitary hyperactivity which would partially suppress the action of insulin 

 and found that after removing a part of the adenoma the insulin resistance 

 disappeared. They seemed inclined to assign some role to the anterior lobe: 

 "Whether in acromegaly the melituria is due to an excess of posterior lobe 

 extract, as the countereffect on insulin would appear experimentally to indi- 

 cate, or to an overactivity of the acidophilic cells of the anterior lobe as we are 

 inclined to believe, or possibly to a combination of both, for we know little 

 of the source of the active substance of the posterior lobe, time will surely tell." 



In 1927 Johns, O'Mulvenny, Potts and Laughton^ observed that extracts of 

 anterior lobe produced slight hyperglycemia and glycosuria. The preparation 

 of the extracts was not published in detail but it was stated that they were 

 free from protein. They may have erred in the last point, because according 

 to our experiments the diabetogenic activity is contained in the protein frac- 

 tion of the extracts. 



3. After ip2p, the Discovery of the Action of the Anterior Lobe on Diabetes. 

 Extending their studies on the hypersensitivity of hypophysectomized animals 

 to insulin, Houssay and Potick" in 1929 confirmed the fact that the hyper- 

 sensitivity appears in toads with no anterior lobe just as in those where the 

 whole hypophysis had been removed. They also discovered that the implanta- 

 tion of anterior lobe from toads or mammals (ox) protects hypophysectomized 

 toads against the action of insulin. This finding led us to study with Dr. 

 Biasotti the influence of hypophysectomy in pancreatectomized dogs and 

 toads. I clearly recall the impression we received when we found that our 

 first hypophysectomized dog did not excrete glucose in the urine during the 

 three days following total pancreatectomy. These results w^ere first published 

 in 1929 by Houssay" in a footnote of a paper in the jubilee volume dedicated 

 to Prof. G. Araoz Alfaro. 



In 1930 Houssay and Biasotti'""'^ published their experiments in detail in 

 three papers. The total removal of the pituitary in dogs'^ or toads^ or of the 

 anterior lobe in the toad"^ produced a great decrease in the intensity of pancre- 

 atic diabetes, also of phlorizin diabetes in the dog."' Implantation or injection 

 of anterior lobe (posterior lobe was much less active) to hypophysectomized- 

 pancreatectomized toads produced severe diabetes.^ 



These experiments allowed us to deduce the following conclusions: (1) the 

 anterior hypophysis has a diabetogenic action; (2) its action on carbohydrate 

 metabolism is physiologic and constant; (3) there exists a certain physiologic 

 antagonism between the anterior hypophysis and the endocrine pancreas 



* In the extensive literature this resistance has been found present in some cases of acro- 

 megaly but lacking in others. In the light of our present knowledge it may be assumed that 

 in the insulin-resistant cases there actually exists an increased secretion of the anterior hy- 

 pophysis, whereas in the nonresistant cases the pancreas had been damaged by an increased 

 secretion of the anterior hvpophvsis which afterwards had sulisided and had become normal. 



