THE METABOLISM OF THE CARBOHYDRATES 705 



adrenal glands and that extracts of the gland, which we must suppose 

 act in the same way as the internal secretion, cause hyperglycemia when 

 injected intravenously (epinephrine hyperglycemia and glycosuria) (page 

 776). 



But on theoretical grounds alone, certain difficulties immediately pre- 

 sent themselves in accepting this as the mechanism by which the nervous 

 system controls the sugar output of the liver, for if increased sugar 

 formation in the liver is dependent on a discharge of epinephrine, the 

 question may be asked why this secretion should be caused to traverse 

 the entire circulation before reaching the liver. 



There are, besides, certain experimental facts which do not conform 

 with such a view. Thus, after complete severance of the hepatic plexus 

 of nerves, stimulation of the splanchnic nerve does not cause the usual 

 degree of hyperglycemia, whereas electric stimulation of the peripheral 

 end of the cut plexus does cause it. On the one hand, therefore, there 

 is evidence that stimulation of the efferent nerve path above the level of 

 the adrenals has no effect on the sugar production of the liver in the 

 absence of these glands; and on the other, we see that when they are 

 present, stimulation of the nerve supply of the liver is effective, even 

 though the point of stimulation is beyond them. There is but one con- 

 clusion that we may draw namely, that the functional integrity of the 

 efferent nerve-fibers that control the glycogenolytic process of the liver 

 depends on the presence of the adrenals, very probably because of the 

 hormone which the glands secrete into the blood. This conclusion is 

 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 observation 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 702). The change may consist 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 at- 



