PHLOIiHIZIX DIABETES (Wi!) 



the synthesis and hydrolysis of phlorhizin would have to occur. He 

 makes it 26 times per minute, which he deems too fast to be probable, 

 but in view of the work which can be accomplished by traces of organic 

 and inorganic carriers (catalyzers, enzymes), this criticism is not con- 

 vincing. 



Whatever the action of phlorhizin may prove ultimately to be, this 

 action finds its chief or final expression in the cells of the kidney, and 

 there leads to a disturbance of equilibrium, whereby the relative blood 

 sugar and urinary sugar concentrations are altered in favor of the urine. 

 The blood sugar must be in equilibrium with the sugar content of the 

 various cells, and this with the sources (glycogen and protein) from 

 which the sugar comes. The sugar of the entire body may be conceived 

 of as a gas exerting its partial pressure in every cell and body fluid, — 

 here more dense, there less so, depending upon local phj-sico-chcmical 

 conditions, but nevertheless everywhere in communication. Piilor- 

 hizin acting in the kidneys, and regardless of a possible action elsewhere, 

 creates a void into which the blood sugar flows, and into which second- 

 arily, as into a vortex, sugar flows from all the sources of the body. 



Metabolic Phenomena.^ — When a fasting dog is kept continuously 

 under the maximum effects of phlorhizin, there is at first a very great 

 glycosuria while the urinary nitrogen remains low. The ratio of the 

 urinary glucose to the urinary nitrogen (G : N ratio) may be as high 

 as 10 or 15 to 1, or higher. If such a dog is killed the liver is found 

 to have a normal appearance and to contain glycogen. As time goes 

 on the rate of glucose excretion falls and the nitrogen tends to increase, 

 until after two or three days the G : N ratio is about 3.65 to 1, as 

 shown by Lusk. Then for 12 to 24 hours it may remain constant. 

 It sometimes happens that the ratio falls to 2.8 or some point between 

 3.65 arid 2.8 before constancy is established. It then proceeds at this 

 lower level instead of 3.65. If a dog is killed at about the time con- 

 stancy is attained, or somewhat sooner, the liver may be found in a 

 state of fatty infiltration with the glycogen low but not absent. In 

 later stages the excessive fat in the liver again disappears. There is 

 then first a rapid loss of glucose and a simultaneous melting away of 

 glycogen. To compensate for the falling out of the carbohydrate 

 from the metabolism there is an increased breakdown of protein and 

 a rapid mobilization of fat, finding temporary expression in a fatty 

 infiltration of the liver. But as the fat reserves run low the fat de- 

 posited in the liver is utihzed. Coincident with the partial exhaustion 

 of the carbohydrate reserves of the body and the increased fat and 

 protein metabolism, acetoacetic and (3-hydroxy butyric acids begin to 

 appear in the urine, and since they are excreted partly in the form of 

 the ammonium salts the urinary ammonia is also increased. These 

 acids arise from lower fatty acids having an even number of carbon 

 atoms in the chain, and from certain amino-acids, whenever the mix- 

 ture of fatty acids and glucose actually metabolizing is too rich in the 

 former in comparison with the latter. 



