802 



PHYSIOLOGY 



be given to the other, which may be regarded as glycogen-free, 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 experiments 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 line of fat 



metabolism, since they are converted into aceto-acetic acid when perfused 



through a dog's liver and the administration 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) : 



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

 glycogen still present in the body. 



