504 DISEASES OF THE INSULAR APPARATUS OF THE PANCREAS 



mals disturbances in the metabolism of sugar. It is true that in certain 

 species of birds this does not go as far as glycosuria, but there results a hyper- 

 glycemia. The significance of the pancreas for the metabolism of sugars is 

 therefore universal. The extirpation of the organ in dogs has been studied 

 the most exactly; I shall therefore make especially the observations in the 

 experiments on dogs the foundation of the following dissertation. The 

 complete removal of the pancreas in dogs always causes a diabetes. The 

 negative results that were obtained by certain investigators, especially those 

 who preceded Mering and Minkowski, and referred to the facts that total ex- 

 tirpation of the pancreas is very difficult, and that sometimes slight remnants 

 suffice to prevent the outbreak of the disease. Luthje has contributed still 

 later reports in which in spite of complete extirpation, the glycosuria remained 

 absent. There occurred, however, as Luthje himself stated, hyperglycemia 

 after the operation, and later histological examinations of the duodenum 

 showed that remnants of pancreatic tissue were present. In more than forty 

 experiments that we ourselves have instituted in the course of the last year, 

 like Minkowski we never missed the occurrence of a severe diabetes. When 

 about a third of the organ is left behind, diabetes usually remains absent, but 

 can, however, develop later if the piece left behind undergoes inflammatory 

 processes. If a still smaller piece of the pancreas is left behind, there occurs 

 a light diabetes, that is, excretion of sugar occurs only when the carbohydrate 

 metabolism is overstrained by the administration of a diet rich in amylaceous 

 material (Sandmeyer's diabetes). 



The sugar that is excreted in the urine after the total extirpation of the 

 pancreas is grape-sugar. The sugar elimination usually starts only a few 

 hours after the operation and in about forty-eight hours the diabetes is at 

 its height. Before the death of the animal the excretion of sugar usually 

 gradually sinks. The duration of life after the operation is at the most 

 fourteen days. Exact information as to the intensity of the excretion of sugar 

 is furnished by the excellent work of Minkowski. This author showed that 

 administration of sugar raises the existing glycosuria by the amount ad- 

 ministered, and further that at the height of the disturbance in metabolism 

 the amount of excreted sugar bears a definite relation to the amount of ex- 

 creted nitrogen. This quotient, D:N, remains 2.8 to 3 [:i], just as well 

 when the dog is fasting as when it is fed with meat or other albuminous body. 

 Minkowski hence drew the conclusion that in this quotient is expressed the 

 extent to which the animal organism is enabled to form sugar out of protein. 

 The animals become poor in glycogen extraordinarily rapidly. After forty- 

 eight hours the liver is almost free of glycogen and later becomes highly 

 fatty. The glycogen is retained in the muscles for a long time, however. 

 Even the leucocytes are strikingly rich in glycogen. Administration of 

 grape-sugar cannot halt the disappearance of glycogen. The power of form- 

 ing glycogen does not however disappear entirely, for on the administration 



