PHLORHIZIN DIABETES (107 



could be split into glucose ('' phlorose") and u subytanee (phlorctin) 

 which by acid hydrolysis yielded phloroglucin and an acid (phlorctinic 

 acid). It was not until 18SC that von Mcrin^^ puhjislied his first 

 experiments upon its physiolofj;ic action. 



While phlorhizin causes glycosuria wiicn taken by mouth, its great- 

 est effect is obtained by subcutaneous injection. One gram of 

 phlorhizin triturated in 5 to 15 c.c. of olive oil, or in 20 per 

 cent, alcohol, and injected subcutaneously once every 24 hours, 

 will maintain the maximum glycosuria which can be produced 

 in a dog of 10 kilogrammes. Phlorhizin is mostly (80-90 per cent.) 

 excreted in the urine. It is soluble in ether, optically active, and gives 

 a garnet coloration with ferric chloride, so that it interferes with the 

 polariscopic tests for )3-hydroxybutyric acid in the urine, and masks 

 the Gerhardt reaction for aceto-acetic acid. 



Phlorhizin causes glycosuria in frogs and other cold-blooded ani- 

 mals, as well as in warm-blooded forms in general, including birds. 

 That geese show glycosuria with phlorhizin (von Mering, Thiel) is 

 important, because birds do not pass sugar in the urine when op- 

 erations are performed upon them which do cause a definite excess 

 of blood sugar (pancreatectomy, Minkowski). Phlorhizin causes 

 glycosuria in birds — hyperglycemia does not. Hence phlorhizin does 

 not cause glycosuria by producing hyperglycemia. In harmony with 

 this syllogism are the data obtained by Minkowski, Levene, von 

 Czylharz and Schlesinger, Lewandowsky, Lepine, Porcher, Junkers- 

 dorf, Erlandsen, Frank and Isaac — all of whom have found the blood 

 sugar concentration in phlorhizinized animals low (0.065 per cent.; 

 0.072 per cent.; 0.012 per cent., etc.). Conflicting results have also 

 been published, but the methods emploj'ed in these ifistances have not 

 usually been beyond criticism (Pavy, Biedle and Kolisch). Even 

 after ligation of the renal vessels or bilateral nephrectomy, no hyper- 

 glj^cemia has been demonstrated in phlorizinized animals, whereas if 

 phlorhizin acted by liberating sugar from glycogen reserves in the 

 liver and elsewhere, or from any source distant from the kidneys, 

 hyperglycemia might be expected. In view of these facts von Mering 

 himself interpreted the action of phlorhizin as a kidney diabetes. 



Zuntz injected phlorhizin directly into one renal artery and col- 

 lected the urine from each kidney separately. The kidney on the 

 injected side almost at once secreted saccharine urine, and the other 

 kidney secreted sugar only after the lapse of minutes. This experi- 

 ment has been successfully repeated by others, and seems to prove 

 that phlorhizin can cause glycosuria by acting directly on the kid- 

 neys. The many experiments which have been made to determine 

 the relative blood sugar content of the renal artery and vein during 

 phlorhizin glycosuria, add little to tliis subject. 



The questions arise: Are the kidney cells the only structures which 

 are directly affected by phlorhizin? and, What is the exact nature of the 

 phlorhizin effect? 



