674 METABOLISM 



corroborated by the fact that stimulation of the hepatic plexus, even 

 with a strong electric current, some time after complete removal of 

 both adrenals, is not followed by the usual degree of excitement of the 

 glycogenolytic process. 



These experiments demonstrate an important relationship between 

 the nervous control, and at least one form of hormone control, of the 

 sugar output of the liver. They indicate that when a sudden increase 

 of blood sugar is required, the glycogenic center sends out impulses 

 which not only directly excite the breakdown of glycogen in the he- 

 patic cells, but also simultaneously influence the adrenals in such a man- 

 ner as to produce more epinephrine in the blood and so augment the ac- 

 tion of the nerve impulse. 



We are as yet quite in the dark as to the mechanism by which the 

 nerve impulses or the hormone brings about increased glycogenolysis. 

 It must consist of a removal of the influence that prevents glycogenolysis 

 from occurring in the normal liver, for it has been shown by direct ob- 

 servation that there is no increase in the amount of glycogenase present 

 in extracts of the liver removed from diabetic animals over that present 

 in extracts of the liver of normal animals. The possible nature of this 

 influence has already been discussed (page 669). The change may con- 

 sist either in a loosening of the combination between the glycogen and 

 the protoplasm of the liver cell, or in a removal of the chemical influence 

 that ordinarily prevents the glycogenase from attacking the glycogen. 

 In the former case the glycogen liberated from its union with the sus- 

 tentacular substances would either become attacked by the glycogenase 

 present in the liver cell itself or it would first of all migrate, as glyco- 

 gen, into "the blood capillaries and there be attacked by the blood 

 glycogenase. Evidence for the possibility of the occurrence of such a 

 process has already been given (page 670). The chemical change re- 

 ferred to under the second possibility might consist in an alteration in 

 the hydrogen-ion concentration of the liver cell, a change, however, 

 which for obvious reasons it is impossible to investigate. 



Nervous Diabetes in Man. The main interest attaching to the inves- 

 tigation of these nervous forms of experimental diabetes depends on the 

 insight which they afford us into the nature of the mechanism by which 

 a prompt mobilization of glucose may be brought about in the normal 

 animal. There is also some evidence that a relationship may exist be- 

 tween certain of the clinical varieties of the disease in man and repeated 

 excitation of glycogenolysis brought about by nerve stimulation. In- 

 creased glucose output from the liver as a result of nerve excitation 

 may be a normal process, but there is reason to believe that frequent 

 repetition of this process tends to induce a permanent rise in the glucose 



