662 DIA BETES 



wliieh can be accomplished by traces of organic and inorganic car- 

 riers (catalyzers, enzymes), this criticism is not convincing. 



Whatever the action of phlorhizin niaij prove ultimately to he, 

 this action, finds its chief or final expression in the cells of the kid- 

 ney, and there leads to a. disturbance of equilibrium, whereby the 

 relative blood sugar and urinarij sugar concentrations are altered 

 in favor of the urine. The blood sugar nnist 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 upoii local physico-chemical conditions, but nevertheless 

 everywhere in communication. Phlorhizin acting in the kidneys, and 

 regardless of a possible action elsewhere, creates a void into which the 

 blood sugar flows, and into which secondarily, as into a vortex, sugar 

 flows from all the sources of the body. 



Metabolic Phenomena. — When a fasting dog is kei)t continuously 

 under the maximum effects of phlorhizin, there is at first a verj- 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 in- 

 crease, 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 and 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 consequent melting away of 

 glycogen. To compensate for the falling out of the carbohydrate 

 from the nieta])olism there is an increased breakdown of i)rotein and 

 a rapid mo])i]i/ation of fat, finding tempoi-ary expression in a fatty 

 infiltration of the liver. But as the fat resei-vcs rnn low tlio fat de- 

 posited in the liver is utilized. Coincident with the ])artial exhaustion 

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

 protein metabolism, acetoacetic and ^-hydroxy butyi-ic acids begin to 

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

 the ammonium sails flic urinary ammonia is also increased. These 

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

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

 ture of fatty acids and L'lncosc actually nictabolizini;- is loo I'icli in 1lie 

 former in comparison willi llic lalio-. 



lTovv('\('r, such animals ai'c not U-i.'^ of <ih-co<i'en. If thev are sub- 



