THE METABOLISM OF CARBOHYDRATES 



845 



second dose of phloridzin be given to the other, which may be regarded as 

 free from glycogen, glycosuria is produced as before, and the excretion of 

 sugar can be continued indefinitely by repeated administration of the drug. 

 So long as sufficient food is given, including carbohydrates, the loss of sugar 

 does not entail any increase in the destruction of the tissues ; but if the drug 

 be administered to starving animals the waste of sugar has to be made good 

 at the expense of material other than carbohydrate. The source of the 

 sugar excreted under these circumstances is the protein of the tissues. The 

 nitrogen excreted in the urine rises in amount in proportion to the quantity 

 of sugar excreted, and there is a constant ratio between the amount of 

 nitrogen and the amount of sugar excreted in the urine. In different experi- 

 ments this ratio D : N varies from 2-8 : 1 to 3-6 : 1. If meat be administered 

 to such starving animals with glycosuria, the D : N ratio does not alter ; the 

 amount of nitrogen in the urine increases, but the sugar increases in the 

 same proportion. The sugar production is therefore proportional to the 

 protein metabolism and must be derived from protein. The source of the 

 sugar is the amino-acids of which the protein is composed. It has been 

 shown by Lusk, Embden, and Dakin that the following amino-acids yield 

 large amounts of glucose when administered to a phloridzinised animal : 

 glycine, alanine, serine, cystine, aspartic acid, glutamic acid, ornithine, 

 proline and arginine. We must assume that these amino-acids produced 

 in digestion or by the autolysis of the tissues undergo deamination and that 

 the sugar is formed by a process of synthesis from the oxyacids thereby 

 produced. On the other hand leucine, tyrosine and phenylalanine give no 

 increase in the output of sugar. It is however just these amino-acids which 

 seem to follow the fine of fat metabolism, since they are converted into 

 aceto-acetic acid when perfused through a dog's liver; and the adminis- 

 tration of fats to phloridzinised dogs is also without effect on the sugar 

 excretion. The drain of sugar from the organism determined by the action 

 of phloridzin on the kidneys thus necessitates a continued breakdown of the 

 nitrogenous tissues of the body in the effort to maintain a normal supply of 

 sugar to the tissues, and unless excessive feeding be employed the animal 

 must waste. The great increase in the nitrogenous output resulting from the 

 condition of phloridzin diabetes is shown in the following table (Lusk) : 





1 The high D : N ratio on the first day is evidently due to the conversion of 

 the glycogen still present in the body. 



