DRUG GLYCOSURIA 521 



causes a transient but marked glycosuria ; as much as 19 per 

 cent, of sugar may be present in the urine of well-fed animals, 

 and from 0.3 to 2.5 per cent, if the animals are starving. The 

 way in which phlorhizin causes glycosuria is not fully deter- 

 mined. It has been generally considered that it acts directly 

 upon the kidneys, so that they excrete sugar from the blood 

 until it contains much less sugar than normal. That the drug 

 acts directly upon the kidney is apparently proved by Zuntz's 

 experiment, which consisted of injecting phlorhizin into one 

 renal artery, with the result that sugar appeared in the urine 

 from this kidney at once, and considerably later in the urine 

 from the other kidney. It would also seem that the excretion 

 of sugar does not depend upon a renal lesion that causes the 

 glomerules to " leak " sugar, but rather upon a direct secretory 

 activity of the kidney, since any disease or injury of the renal 

 tissue diminishes or prevents the glycosuria following phlorhizin 

 administration, although phlorhizin itself causes necrotic changes 

 in the renal epithelium. 



However, these views have been vigorously opposed. Pavy 

 claims that the blood in phlorhizin diabetes does not contain less 

 sugar than normal, indeed, he found that it might contain 

 more, but his results are in contradiction to those of many 

 others, who have found a decreased amount of sugar in the 

 blood (fiypoglycemia) as a characteristic feature of phlorhizin 

 diabetes. Pfliiger questions Zuntz's results on the ground that 

 the sugar observed in the urine might have come from the 

 phlorhizin itself, through splitting, and questions the justifica- 

 tion of considering phlorhizin glycosuria as a special, peculiar 

 form of glycosuria, differing from all other forms, which 

 depend upon a hyperglycemia. 



After repeated doses of phlorhizin, the glycogen may disap- 

 pear to a large extent from the liver, and also from the muscles, 

 but the reduction is by no means so marked as in some other 

 forms of glycosuria. Apparently, phlorhizin does not act upon 

 the glycogenic function of the organs, but simply causes a drain- 

 ing away of sugar, to replace which the glycogen is converted 

 into sugar. Corroborating this view is the fact that if the 

 kidneys are tied off, administration of phlorhizin does not 

 cause a rise in the amount of sugar in the blood. 



If an animal to which phlorhizin is being repeatedly given is 

 starved, the elimination of sugar does not cease, but continues 

 at a low level, while at the same time the elimination of nitro- 

 gen is increased until a maximum constant ratio of nitrogen to 

 sugar is established, with the proportion of dextrose to nitrogen 



