B. A. Houssay 253 



(in 1940) it was stated that "not all the diabetogenic effect of the anterior 

 pituitary is mediated by the adrenal cortex, but rather that a synergism exists 

 between these two hormones." The proof of the diabetogenic action of antero- 

 hypophysial extracts in animals without adrenals was presented in the toad 

 by Houssay and Biasotti'""" in 1933 and 1936 and by Houssay and Leloir™ in 

 1935, and in adrenalectomized dogs with reduced pancreas, kept alive with 

 adrenal extract (Houssay and Biasotti^" in 1938) or with desoxycorticosterone 

 or only with sodium chloride (unpublished experiments™). While we do not 

 discard the possible existence of the synergism between anterohypophysis and 

 corticoadrenal hormones, in the latter experiments no such synergism was 

 detectable. Concerning participation of the adrenals in anterohypophysial 

 action we shall publish some other experimental results later. 



F,. Permanent Diabetes hiduced by Anterohypophysial Extracts. In 1932 

 Houssay, Biasotti and Rietti''''''" proved that the injection of anterohypophysial 

 extract into normoglycemic dogs with reduced pancreatic mass produces a 

 diabetogenic action. After the interruption of the injection the majority of 

 the animals returned to a normoglycemic state, but some remained perma- 

 nently diabetic until death. This was the first demonstration of permanent 

 diabetes due to the action of anterohypophysial extract. 



In 1937 Young" reported the very important verification, namely, that this 

 particular permanent diabetes can be produced in normal dogs. His remark- 

 able work was duly appreciated and the doubts of some concerning the antero- 

 hypophysial diabetogenic action definitely subsided. Summaries of these works 

 were published by Young"^""^ in 1939 and 1940. 



A year before, in 1936, Houssay and Foglia'" demonstrated that the pancreas 

 of dogs with hypophysial diabetes showed a decrease in its capacity to secrete 

 insulin. This was confirmed in 1941 by Houssay, Foglia, Smyth, Rietti and 

 Houssay"" who also showed that if the dog resists the diabetogenic action and 

 remains normoglycemic, or in case his diabetes subsides, tJie pancreas in 

 many instances has a normal (and sometimes supernormal) secretion of 

 insulin. 



Richardson"" and Young"" have shown that during anterohypophysial dia- 

 betes the beta cells show a disappearance of granules, vacuolization and 

 pyknosis; in case the animal remains with a permanent diabetes the islets 

 are found atrophic, hyalinized, with few or no beta cells. If the animal resists 

 the extract or if his hyperglycemia subsides, recuperation of the beta cells 

 can be observed, as shown by Porto." 



Actually the anterohypophysial extract produces two kinds of diabetes: 



(1) the appropriately designated anterohypophysial diabetes observed during 

 the injection of the extract; its origin is due first to extrapancreatic factors 

 for only afterwards are the islets injured and the secretion of insulin dimin- 

 ished. There is in these animals characteristic increase in resistance to insulin; 



(2) permanent diabetes, which is pancreatic and should be called metahypo- 

 physial diabetes, being due to the lack of active Langerhans islets; the antero- 



