INTERMEDIATE METABOLISM OF THE FATS 399 



muscles is brought about by the lactic acid and even, in part, by the 

 carbon dioxide which accumulates in fatigued muscles. 



The Creatine content of muscular tissues is not decisively affected by 

 muscular work. It appears that the increase, if any, is very slight, a 

 fact which corresponds to the subordinate part which is normally 

 played by proteins in the development of muscular energy. Neverthe- 

 less Van Hoogenhuyze and Verploegh have found a definite increase 

 of creatine in muscular tissues after severe work, provided the work 

 was performed by starving animals. In other words if protein is of 

 necessity employed by the muscles as a source of energy, then creatine 

 is numbered among the chemical products of muscular work. The 

 production of creatine appears, however, to bear an especial significance 

 in relation to muscular Tonus; any agent tending to increase the tonic 

 contraction of the muscles leading to an increased creatine-content. 

 Thus the creatine-content of the muscles is increased by drugs such as 

 Cinchonine which increase tonus, and in pregnancy the creatine-content 

 of the muscular tissues of the Uterus is very greatly increased. 



THE INTERMEDIATE METABOLISM OF THE FATS; DIABETES. 



The normal products of the oxidation of the fats and sugars are 

 finally, as we have seen, carbon dioxide and water. In animals with 

 normal metabolism, but few of the intermediate products of oxidation 

 can be perceived, because the various stages are passed through rapidly 

 when the oxidation is once begun, and intermediate products of the 

 process, therefore, have no opportunity to accumulate. One stage 

 which is easily recognizable is that afforded by the production of 

 Lactic Acid because the next step in the oxidative processes is evidently 

 accomplished with relative difficulty, so that a proportion of this prod- 

 uct accumulates in the tissues, especially if the oxidative processes 

 are interfered with so as to increase the difficulty of further transfor- 

 mation. Our knowledge of other stages, in the oxidation-processes 

 of the body is, however, very largely derived from an experiment which 

 is performed for us by nature in the disease or group of diseases known 

 as Diabetes Mellitus. 



Glycosuria, the excretion of sugar in the urine, may be induced by 

 the injection of physiologically unbalanced Salt Solutions and particu- 

 larly by solutions containing Magnesium Salts. The origin of this 

 glycosuria, whether it arises from an unusual discharge of sugar from 

 the muscles or the liver, or from an increased permeability of the 

 kidneys for sugar, has not as yet been ascertained. A glycosuria 

 without any accompanying Glucohemia, that is, without any increase 

 in the normal percentage of sugar in the blood, may be induced by the 

 administration of the glucoside Phloridzin. This glycosuria is evidently 

 due to an alteration of the normal Permeability of the kidney for sugar. 

 The epithelium of the normal kidney interposes an impassable barrier 



