METABOLISM 523 



The Release of Sugar. The necessity for a release of carbohydrate 

 material from the storage tissues, and more especially from the liver, arises 

 from the fact that the circulating sugar which readily passes into the 

 muscle tissues is promptly oxidized, and hence the sugar content of the 

 blood rapidly falls below the normal and a condition of hypoglycemia is 

 temporarily established. With the establishment of this condition the 

 liver cells transform a portion of the glycogen into glucose by the addition 

 of the molecule of water, and as the sugar is highly diffusible, it passes 

 across the wall of the capillary vessel into the blood and thus restores the 

 sugar content and brings it up to normal. This procedure continues until 

 the necessity arises for the consumption of a new supply of food materials. 

 From the foregoing fact the liver is said to possess a sugar-forming or a 

 glycogenetic function. To this transformation of glycogen into sugar the 

 term glycogenolysis has recently been applied. 



The question now arises, by what agency or mechanism are the liver 

 cells stimulated to release the glycogen and transform it into sugar and 

 discharge it into the blood in amounts just sufficient to replace the sugar 

 oxidized, without giving rise to hyperglycemia and glycosuria? 



Influence of the Nerve System. That the nerve system is in some way 

 concerned in the regulation of sugar formation in the liver is apparent 

 from the effects that follow certain lesions of the nerve system, whether 

 established by pathologic processes, experimental procedures, or psychic 

 states such as major emotions, prolonged anxiety, etc.; but whether the 

 regulation is direct (i.e., through its action on the liver cells) or indirect 

 (i.e., through its action on glands of internal secretion) e.g., adrenals and 

 hypophysis is a subject of discussion and experimentation. 



It is well-known fact that if the floor of the fourth ventricle is punc- 

 tured at a point between the origin of the acoustic and vagus nerves, 

 near the middle line, a glycosuria will be established in from one to two 

 hours, and which will last from five to six hours in the rabbit, ancj from 

 three to seven hours in the dog. Coincidently there is an increased 

 amount of sugar in the blood (hyperglycemia) and a higher percentage 

 of sugar in the liver than is normally the case. Apparently the initial 

 step in this series of phenomena is an increased conversion of glycogen 

 into glucose, increased glycogenolysis. This supposition receives con- 

 firmation from the fact that the degree of the hyperglycemia and gly- 

 cosuria is determined by the amount of glycogen previously present in 

 the liver. If the percentage of glycogen is high, the resulting glycosuria 

 is pronounced; if the percentage is low, as it will be after a fast of several 

 days' duration, the glycosuria will be slight or entirely wanting. The 

 foregoing fact, together with other facts derived from the fields of path- 

 ology and clinical medicine, has led to the view that there is in the medulla 

 oblongata a group of cells which through efferent fibers influence the 

 production of sugar in the liver. From the further fact that the glyco- 

 suria is but temporary in character the inference is that the puncture 

 stimulates rather than destroys these cells. This view is corroborated by 

 the fact that a similar glycosuria is established by psychic states of an 

 emotional character e.g., fear, and injuries to sensory nerves in different 

 regions of the body. In either case the nerve impulses so developed in 

 the cerebrum or in the periphery are transmitted to the group of cells in 



