•Mil. METABOLISM OF THE CARBOHYDRATES 663 



conditions under which glycogen may be formed in the liver; thai is, 

 whether it is formed exclusively from absorbed sugar, or whether other 

 substances, such as protein and fa1 may also form it. The importance of 

 such knowledge rests in the fad thai in severe diabetes, sugar continues 



to be added to the blood, although do sugar is being taken with the f I. 



To check the hyperglycemia in such cases i1 becomes necessary, therefore, 

 to curtail the did uo1 only with regard to its carbohydrate content, bul 

 also with regard to whatever other foodstuff may be capable of causing 

 glycogen formation. The practical question therefore is. What arc these 

 foodstuffs? There are two methods by which the problem may be investi- 

 gated. The first, which we may call the direct method, consists iii rendering 



the liver free of glycogen and then some time afterward £ ling the animal 



with the foodstuff in question, afterward killing it and examining the liver 

 for glycogen. The other, which we may call the indirect method, con- 

 sists in first of all rendering the animal incapable of oxidizing glucose — 

 that is. making it diabetic — and then proceeding to see whether the in- 

 gestion of a given foodstuff causes an increase in the sugar exeretion in 

 the urine. The methods for rendering an animal experimentally diabetic 

 will he considered later; for the present it is important to note that, if 

 a diabetic animal excretes more glucose while fed on a given foodstuff. 

 we may infer that the normal animal would convert it into glycogen. 



The results of the direct method are much less reliable than those of 

 the indirect for the reason that it is extremely difficult to remove all 

 traces of glycogen from the liver. The methods employed for this pur- 

 pose have consisted in: (1) starvation of the animal; (2) muscular ex- 

 ercise; (3) exercise and starvation combined; and (4) the production of 

 certain forms of experimental diabetes — for example, that produced by 

 phlorhizin. Starvation alone is unsatisfactory, for it has been found 

 that, although a1 certain stages of this condition the liver may become al- 

 most entirely free from any trace of glycogen, at a later stage glycog 

 may again make its appearance. It is therefore most difficult to decide 

 at what stage in starvation the animal should be considered as glycogen- 



frec. 



If the starving animal is made to perform muscular exercise, coin]) 1 

 removal of glycogen from the liver can be depended upon. The exer 



may be produced by the administration of strychnine in such dosage as 



just to produi nvulsions of the voluntary muscles without permanent 



contraction of those of respiration. The most useful method, however. 

 consists in starving the animal for a few days and then placing it in a 

 cold, damp room, after giving it a cold hath. The evaporation of m 

 ture from the surface so cools the body down that the stores of glycogen 

 all become used up in the attempt to supply fuel for the production of 



