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Experimental Pancreatic Diabetes

pancreas, extirpation, disease, glycosuria, sugar, excretion and produced

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EXPERIMENTAL PANCREATIC DIABETES.

Of much more far-reaching significance, and of immense im portance for the fundamental doctrines of biology, is another form of experimental glycosuria. This is the diabetes mellitus occurring after extirpation of the pancreas.

I employ here for the first time the term "diabetes mellitus" to designate an artificially produced glycosuria. I have hitherto inten tionally avoided the expression because we have until now been con sidering a rapidly evanescent excretion of sugar which survived hardly more than a few hours the injuriously acting interference. In the case of extirpation of the pancreas, however, things are different; for we have here as the result a chronic disease which continues to the end of life.

After many clinical facts bearing upon the relation between pan creatic disease and diabetes mellitus had been recorded (Lancereaux and others), and after many experimenters had endeavored with lit tle or no success to cause a glycosuria by extirpation of the pan creas, division of the nerves supplying the organ, or ligation of the pancreatic duct, the question was taken up anew and elucidated by v. Mering and Minkowski (1890). We are ready to give full credit to the Italian scientist de Dominicis for having undertaken, simul taneously and independently of the above-named authors, the same researches and for having arrived at practically the same results. Nevertheless, from a biological standpoint he did not treat the ques tion so well or so carefully as did v. 3Iering and Minkowski, and consequently his investigations had less influence upon the development of this important question.

When the pancreas of a dog is completely extirpated a severe form of diabetes is developed within twenty-four hours, which leads to the death of the animal in a few weeks. The disease is denomi nated "severe" because the excretion of sugar continues even when all carbohydrates have been abstracted from the food. The disease thus produced resembles in every particular grave diabetes in man, for, besides the chronic glycosuria, we find polyphagia, polydipsia, polyuria, hyperglycemia, excessive destruction of albumin, emacia tion, loss of strength, excretion of large quantities of aceton, aceto acetic acid, oxybutyric acid and ammonia, coma and death. The

sugar excreted is, as in the disease in man, grape sugar.

Besides the discoverers of the affection, the following investiga tors have made contributions to our knowledge of pancreatic dia betes: Lepiue, Arthaud, Butte, Remond, Hedon, Glee, Thiroloix, and Lancereaux in France ; de DOM inicis, de Renzi, Reale, and Gaglio in Italy ; and Aldehoff and Saudmeyer in Germany. Some of these authors have been unable to confirm in every respect the accounts of the discoverers, since they were not always fortunate enough to induce diabetes or were able to cause a transitory glycosuria only. Min kowski, however, has shown conclusively that all these failures to produce the expected result were to be explained by defective methods of research. Extirpation of the pancreas in the dog is, indeed, an uncommonly difficult operation; small portions of the gland may very readily be left in the body, and are with difficulty to be dis covered in the cicatricial tissue at the subsequent autopsy. But when the pancreas has not been entirely removed the occurrence of diabetes is not to be expected (see below).

Omitting minor details, the most important points which have been established concerning experimental pancreatic diabetes are the following: I. Diabetes has, up to the present, been artificially produced by extirpation of the pancreas in the following-named animals : dogs, cats, pigs, carnivorous birds, frogs, and turtles. Most of the experi ments, however, have been carried out upon clogs, and what follows relates to the results of experiments upon this animal.

2. Diabetes occurs in dogs only when the pancreas has been totally removed, but then regularly. Assertions opposed to this statement are growing constantly fewer, while those in agreement therewith are as steadily increasing in number. The same results have been commonly, though not invariably, obtained after the injec tion of warmed paraffin into the duct of Wirsung. The paraffin hard ens upon cooling and plugs up the ducts, the result usually being complete atrophy of the entire gland.

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