676 METABOLISM 



HORMONE CONTROL AND PERMANENT DIABETES 



Nervous excitation can explain only transitory increases in blood sugar, 

 the more permanent hyperglycemias being dependent upon some dis- 

 turbance in the hormone control of carbohydrate utilization. This dis- 

 turbance is a much more serious affair than that produced by nervous 

 excitation. In the latter case the hyperglycemia ceases whenever all 

 of the glycogen stores of the liver have been exhausted; whereas a dis- 

 turbance in the hormone control, besides causing as its first step a 

 breakdown of all the available glycogen, goes on to cause a production 

 of sugar out of protein. A process of gluconeogenesis (new formation 

 of glucose) becomes superadded on one of glycogenolysis. 



To ascertain the nature of this hormone and the mechanism of its 

 action has been the object of most of the researches on those forms of 

 diabetes that are produced by changes in certain of the ductless glands. 

 The following possibilities may be considered: (1) that the controlling 

 agency is the concentration of glucose in the blood; (2) that it is the 

 presence in the blood of decomposition products of glucose; (3) that it 

 is due to a special hormone produced from some ductless gland. Con- 

 cerning the first of these possibilities, it is supposed that the mechanism 

 involved is dependent on the law of mass action ; namely, that glycogen be- 

 comes converted into glucose whenever the blood flowing to the liver con- 

 tains less than its normal concentration of glucose, and conversely, when this 

 blood contains an excess of glucose, as during absorption, that a glycogen- 

 building process occurs. Although there can be little doubt that the process 

 of glycogen formation or destruction will depend to a certain extent 

 upon the amount of glucose present in the blood flowing to the liver 

 cells, yet it is impossible that this can be an important means in the 

 control that exists between sugar production by the liver and sugar 

 consumption by the tissues, because the sugar that is added to the portal 

 blood during absorption would mask any depletion caused by sugar 

 consumption in the tissues. 



The second possibility that the hormone is some decomposition prod- 

 uct of glucose would appear to have some support, if we consider this 

 hormone to be an acid product (carbon dioxide or lactic acid) produced by 

 sugar metabolism, for it is known that an increase in the hydrogen-ion 

 concentration of the blood flowing to the liver cells excites a glycogen- 

 olysis. As we have already seen, however, it is difficult to secure ex- 

 perimental evidence, in anesthetized animals at least, that glycogen- 

 olytic activity is readily excited in this way. 



The third possibility that some specific hormone may exist in the 

 blood exciting the glycogenolytic process is investigated by producing 



