^ 1 o Pituitary and Carbohydrate Metabolism 



betes by the administration of APE* to so-called "Houssay" animals and later 

 to normal animals of many species. Permanent diabetes, lasting long after the 

 cessation of APE injections, was first observed by Evans and collaborators and 

 later extensively studied by Young,' Campbell and Best,'' Dohan, Fish and 

 Lukens," and others. This permanent diabetes, observed so far only in dogs, has 

 now been ascribed to damage to the pancreatic islets induced by unknown 

 mechanisms during the prolonged administration of APE. The temporary 

 diabetes first observed, however, continues to be considered of direct pituitary 

 origin. All these observations have been many times confirmed, and many 

 other metabolic effects of APE have also been demonstrated— the glycotrophic 

 or anti-insulin effect (in which all trace of insulin action may be prevented by 

 suitable preparatory administration of APE to the experimental animals), the 

 pancreotrophic effect, the power of increasing the content of liver fat by trans- 

 ference of fat from peripheral depots, the ketogenic factor, and the glycostatic 

 effects— among them. 



In recent years, in work on small animals such as the rat and rabbit, it 

 has been possible to investigate the role of the anterior pituitary in metab- 

 olism with more precision than is usually possible in larger animals, such as 

 the cat and dog, in which most of the earlier work was done; and most of the 

 work defining the interrelationships of the hormones has been carried out on 

 the smaller animals. In the rat, rather complete studies have been made of the 

 effects of hypophysectomy upon the metabolism of carbohydrate. Hypophysec- 

 tomized rats, like other species of such animals, exhibit atrophy of the thyroid, 

 adrenals, and gonads, and fail to grow, but as long as they are well fed, they 

 do not show any great abnormalities in their metabolism of carbohydrate 

 except an extreme hypersensitivity to insulin. However, when these animals 

 are fasted, differences from the normal are at once apparent. In as short a time 

 as eight hours after the removal of food, glycogen is found to have disappeared 

 almost entirely from the liver, and the blood sugar has begun to fall rapidly. 

 At about this time the muscle glycogen content begins to fall, and by the time 

 the animal has been fasting 16 to 18 hours, the muscle glycogen may be only 

 half its normal value, whereas of course in normal animals the muscle glycogen 

 is ordinarily quite stable for long periods of fasting.'' During this period of 

 carbohydrate depletion, the RQ of the hypophysectomized rats is higher than 

 that of the normal, and sufficiently so to indicate that the rapid rate of glycogen 

 loss could have been due to more rapid oxidation of carbohydrate.' Similar 

 studies have not as yet been completed in other species than the rat; but the 

 loss of liver glycogen and rapid decline of the blood sugar has been observed 

 frequently. Cope' and others have shown clearly in hypophysectomized rabbits 

 that a rapid loss of liver glycogen and subsequent decline in the blood sugar 

 sets in dur ing fasting and something like this situation also is found in hy- 



* APE refers to anterior pituitary extracts, without distinguisliing between any of the 

 various types of extract. In most cases a crude, or at least not highly purified, extract was used, 

 which contained many of the several anterior pituitary factors. 



