128 The Endocrine Organs 



augmented by the fact that the permeability of the kidneys to blood-sugar 

 seems also to be somewhat increased by absence of the pancreas. The 

 hyperglycsemia is produced in the first instance by transformation of the 

 liver glycogen into sugar, which is passed into the blood ; while the glycogen 

 of the muscles is also diminished. 1 The sugar thus produced from the liver 

 glycogen is not utilised in the body, but is for the most part at once got rid 

 of by the kidneys. Since, therefore, the carbohydrates of the food are not 

 used for nutrition, there is a comparatively greater call upon the proteins 

 and fats both of the food and of the body, so that the animal loses flesh 

 rapidly and death may ultimately result from inanition, unless the end has 

 arrived sooner as the result of the accumulation in the body of abnormal 

 by-products of the metabolism of proteins and fats (such as the acetone- 

 bodies) tending to acidosis and the production of diabetic coma. 



Kausch, and independently Noel Paton, have shown that in birds re- 

 moval of the pancreas does not cause glycosuria although hyperglycaBinia is 

 produced ; on subsequently administering adrenalin, glycosuria supervenes. 



NATURE OF THE PANCREATIC AUTACOID 



The results of pancreas extirpation and pancreas grafting can, as we 

 have seen, be best explained by supposing that the islet tissue produces 

 an autacoid which passes into the blood and affects carbohydrate meta- 

 bolism and carbohydrate storage in such a manner that there is no undue 

 accumulation of glucose in the blood. Provisionally, it will be convenient 

 to refer to this hypothetical autacoid as insuline. It must, however, be 

 stated that it has yet to be determined whether the active substance is 

 present as such in the pancreas or whether it exists there as pro-insuline, 

 which becomes elsewhere converted into the active autacoid. It is not found 

 that pancreas extracts have the effect of antagonising the results of pancreas 

 extirpation : in this respect they offer a parallel to the negative results of 

 suprarenal extracts in antagonising the effects of adrenal deprivation. On 

 the other hand, it has been shown by Hedon and others that the blood of a 

 normal dog contains substances which, when allowed to circulate through 

 the system of a depancreatised dog, prevent the occurrence of glycosuria. 

 It has also been shown by Carlson and Drennan that if a pregnant bitch 

 be deprived of the pancreas she does not suffer from glycosuria as long as 

 her foetuses remain in utero. This experiment indicates that the autacoids 

 produced by the fretal pancreas can pass to the maternal circulation through 

 the placenta ; and both experiments afford a clear indication that the influ- 

 ence of the pancreas upon carbohydrate metabolism is due to a chemical 

 agent circulating in the blood. Later experiments of Hedon seem to show 

 that the autacoid is inactive whilst within the pancreatic vein, and only 

 becomes activated on passing through the liver. 



] Ehrlich found the glycogen of the blood-leucocytes to be markedly increased in amount 

 in pancreatic diabetes. 



