702 A. S. WAKTHIN 



others noted also the relationship between pancreatic changes and diabetes 

 without advancing the solution of the problem. In his work on diabetes 

 published in 1884, Frerichs states that atrophy, fatty infiltration and in- 

 durative conditions of the pancreas have often been seen in diabetes, and 

 mentions two cases of his own, one of carcinoma of the head of the pancreas 

 with stenosis and dilatation of the pancreatic ducts, the other with calculus 

 obstruction of the duct, cystic dilatation and atrophy of the entire gland. 

 He concludes that the pancreas, as a gland, as shown by Haidenhain, Klebs 

 and Munk, and others has no influence on the excretion of sugar through 

 the kidneys; and that it is undecided whether morbid conditions of this 

 gland or its neighboring tissues could stimulate the coeliac plexus and 

 thereby cause diabetes, since experimental work upon the abdominal nerves 

 has led to uncertain results. 



Demonstration of the Sugar Function of the Pancreas. In 1889-90 

 appeared the classical work of von Mering and Minkowski which laid 

 the cornerstone for the future conception of the pancreas as an endo- 

 crin organ. Conquering the difficulties of the operation they succeeded 

 in obtaining complete extirpation of the organ, finding that dogs so 

 depancreatized developed without exception a true permanent diabetes 

 mellitus, glucose appearing in the urine as early as 4 to 6 hours after the 

 operation, but usually later, often on the next day, reaching its height 

 during the first 24 to 48 hours, even to 5 to 11 per cent before the animal 

 received any nourishment. Even in dogs starved for seven days, the sugar 

 did not disappear from the urine; when abundant food was taken larger 

 amounts of sugar were excreted in the urine. Other symptoms of diabetes, 

 as in man, were present in the form of hunger, thirst, polyuria, rapid ema- 

 ciation and loss of strength. The sugar of the blood was increased. Sooner 

 or later, in certain cases, acetone, acetoacetic acid and oxybutyric acid ap- 

 peared in the urine. The glycogen content of the organs was early reduced 

 to very slight traces. The diabetes persisted until the death of the animals, 

 none of them living longer than four weeks. At autopsy the complete ab- 

 sence of the pancreas was confirmed. Marked fatty change of the liver 

 was, also, a constant finding. From these experiments the investigators 

 considered the diabetes to be the direct result of the total extirpation of the 

 pancreas. When only a portion of the organ was removed no diabetes re- 

 sulted. Only when the remaining portion of the gland was removed did 

 the animal become diabetic. Injury to the solar plexus wae also excluded. 

 Ligation of the ducts was not followed by diabetes. Von Mering and 

 Minkowski regarded their experiments as proving absolutely that the 

 cause of diabetes was not the result of the absence of the pancreatic juice 

 in the intestine ; and concluded that the total extirpation of the pancreas 

 must cause a disturbance of the intermediary metabolism within the organ- 

 ism. Diabetes must be the result of the loss of a specific, hitherto un- 

 known, pancreatic function which is necessary to the consumption of 



