720 PRINCIPLES OF GENERAL PHYSIOLOGY 



The Internal Secretion of the Pancreas. Mering and Minkovski (1889) showed 

 that complete removal of the pancreas invariably results in severe diabetes 

 mellitus. The animals excrete large amounts of glucose, even if no carbohydrate 

 food is given. They show great hunger and thirst, and, in spite of liberal food, 

 they die of inanition in the course of two or three weeks, or less. To obtain this 

 result extirpation must be complete ; one fifty-fifth of the organ suffices to prevent 

 the symptoms. Since total extirpation is of primary importance for success, the 

 excellent method of removal introduced by Hedon (1910) may be referred to. 



The glycogen vanishes from the liver in pancreatic diabetes, and although the 

 glucose content of the blood may be raised to 0-8 per cent., no glycogen is stored, 

 although it has been stated that fructose may give rise to glycogen in the liver. 



The meaning of this great loss of glucose is still obscure. Investigations 

 directed towards testing the power of the tissues to consume carbohydrate have 

 not been able to show that the power is entirely wanting (see the paper by 

 Patterson and Starling, 1913), although it seems to be diminished, especially in the 

 later stages. 



Although no attempts to prevent the diabetes by the injection of extracts 

 of pancreas have been successful, the transfusion experiments of Hedon (1913) 

 show that the glycosuria is due to the absence of a hormone secreted by the 

 normal pancreas. An anastomosis was made between the vein of the pancreas 

 of a normal dog and the jugular vein of a depancreatised and diabetic dog. The 

 glycosuria was almost abolished, and there was a diminution in the glucose content 

 of the blood. That the liver plays an important part in the process is shown 

 by the following variation of the experiment. A part of the normal pancreas of 

 another dog was intercalated, by vascular anastomosis, in the circulation of a 

 diabetic dog. This had a similar effect to the previous form of experiment, 

 but only when the venous blood of the pancreas, presumably containing the 

 hormone, was allowed to pass through the liver, by anastomosis with the splenic 

 vein of the diabetic dog. The serum of the venous blood of the pancreas is 

 said to have no anti-diabetic power. The fact of the relatively small effect on 

 the glucose content of the blood leads Hedon to the view that the hyperglycsemia 

 and the glycosuria are more or less independent. The blood sugar may be 

 scarcely diminished at all when its excretion by the kidneys ceases owing to 

 the influx of normal blood. But, since the blood sugar did not increase, it is 

 clear that either the excess production had been retarded, or the rate of 

 consumption by the tissues increased ; otherwise it must accumulate when 

 excretion stops. These experiments indicate, then, (1) that the liver plays an 

 important part, and (2) that there is some influence exerted by the pancreatic 

 hormone on the excretion of sugar by the kidneys. This latter may be either 

 decreased permeability, or, perhaps more probably, an effect on the reabsorption 

 in the tubules of the glucose contained in the glomerular filtrate. A third 

 possibility is suggested by Hedon, namely, that there might be some change in 

 the state in which the sugar exists in the blood. 



In connection with these results, the experiments of De Meyer (1906-1910) 

 are of interest. He finds that the liver, perfused with Ringer's solution, loses 

 less glycogen if pancreatic extract is added. If the liver came from a 

 depancreatised animal, it was found that its function of storing glycogen could 

 be restored by the perfusion of fluids containing pancreatic extracts. Perfusion 

 with blood, instead of with Ringer's solution, showed still more marked effects 

 of addition of pancreatic extract. Perfusion of the kidney with Ringer's solution 

 containing glucose, together with pancreatic extract, showed that considerably 

 less sugar came out in the secretion than in the absence of pancreatic extract. 

 De Meyer finds that the addition of such extract to solutions of glucose -does 

 not diminish its rate of diffusion through a colloidal membrane, and interprets 

 the effect as being due to a diminution of the permeability of the kidney for 

 glucose. It might, of course, be exerted on the power of reabsorption. The 

 experimenter is inclined to attribute the action, both in the case of the liver 

 and the kidney, to the increase of hydrogen ion concentration in the blood in 

 diabetes, which is counteracted by the internal secretion of the pancreas. 



