THE METABOLISM OF THE CARBOHYDRATES 703 



edly depressing their activities. That a tendency to increasing acidity in the liver 

 cells may accelerate the breakdown of glycogen is suggested by the depressing effect 

 produced on the assimilation limit of sugars by administering acids, and by the ob- 

 servation that postmortem glycogenolysis becomes marked in proportion as the dying 

 liver becomes acid in reaction. It might be thought then that glycogenolysis in the 

 liver cell could be set up by the local production of a certain amount of acid. Such 

 a liberation of free acid could be brought about by a curtailment in the arterial blood 

 supply of the hepatic cell, producing a local accumulation either of carbonic or of other 

 less completely oxidized acids (e. g., lactic). It may be that asphyxia causes hyper- 

 glycemia by such a mechanism. Vasoeonstriction and consequent curtailment of ar- 

 terial blood supply occurs in the liver when the hepatic nerves are stimulated, and 

 it is possible that the glycogenolysis which is also set up by such stimulation is due to 

 the appearance of acids. The accelerating effect of epinephrine on glycogenolysis might 

 also be explained as due to limitation of blood supply on account of vasoconstriction 

 and local asphyxia. 



THE REGULATION OF THE BLOOD SUGAR LEVEL 



The level at which the concentration of sugar in the systemic blood 

 is maintained represents the balance between two opposing factors: (1) 

 the consumption of glucose bv the tissues, and (2) the production of 

 glucose by the liver. Since this is the most readily oxidizable of all 

 the proximate principles of food (page 685), muscular activity causes 

 large quantities of it to be consumed, so that its concentration in the 

 blood tends to fall below the physiological level, a tendency which is 

 immediately met by an increased discharge of glucose from the liver. 

 The question therefore arises as to how the muscles or other tissues 

 transmit their requirements for glucose to the liver. There are two 

 possible ways by which this could be done: (1) by means of a nervous 

 reflex, or (2) by changes in the composition of the blood, either with 

 regard to the percentage of sugar itself or because of the appearance in 

 it of decomposition products of glucose or of some special exciting 

 agent or hormone. 



In order to ascertain the relative importance of these methods of 

 correlation between the places of supply and demand of glucose in the 

 normal animal, it is necessary to investigate the conditions under which 

 an excessive discharge of glucose occurs either because of overstimulation 

 of the nervous control, or because of the presence of exciting substances 

 (hormones) in the blood. The glycogenolytic function can be excited through 

 the nervous system in a variety of ways so as to cause hyperglycemia 

 and glycosuria. This constitutes one form of experimental diabetes. In 

 laboratory animals mechanical irritation of the medulla oblongata and 

 stimulation of the great splanchnic nerves act in this way. Similar stimula- 

 tion may also occur under certain conditions in man. Excitation as a result 

 of changes in the composition of the blood can be produced experimen- 

 tally by certain drugs (phlorhizin), or by the removal of certain of the 



