TIIEOUY OF DIMiKTES, 675 



irrcvcrsiblo, although it mij^ht luivc; (\\i.st(Ml iiujiucnturily in tlic Ixjdy 

 as glycogen or other isomer of ghicosc. What j)haHe in tin; utihzation 

 of this glucose is primarily disturbed is another fjuestion. To say 

 that 40 grams of ingested glucose causes the appearance of 40 grams 

 of extra sugar in the urine does not prove that tlu; diabetic body is 

 inherently incapable of using any sugar or every carbohydrate. It 

 might still be capable of using a two, three, or four carbon atom sugar, 

 some other member of the group of 32 hexoses, or, as some have it (von 

 Noorden), sugar which has first been built up into glycogen, etc., 

 provided these substances could be kept from undergoing transfor- 

 mations into the non-utilizable glucose. As a rule, however, when 

 other sugars are fed to complete diabetics, they are transformed into 

 glucose and appear as such in the urine. This phenomenon has much 

 of significance for the general theory of sugar metabolism and is an 

 indication of the nature of the primary disturbance in diabetes, as will 

 now be shown. 



Theory of Diabetes. — What sort of a chemical process is involved 

 when levulose, for example, is converted in the body into glucose? 

 As already stated in the chemical introduction, the reciprocal trans- 

 formations of hexoses one into another in the alkaline solution in 

 vitro depend upon a preliminary ionization of the sugars followed by salt 

 formation, the salts then undergoing dissociation which, according 

 to Mathews and Michaelis, is still purely electrolytic with rearrange- 

 ments of the anion; but which, according to Nef, is a non-electrolytic 

 dissociation of the type which he calls methylene dissociation. Some 

 form of dissociation must he a prelude also to these transformations in 

 the body. This view is logically just as necessary as it has been found 

 to be for the organic chemist, and, it may be added, that for the oxida- 

 tion of sugars as well as for their polymerization a preliminarj' dissoci- 

 ation is essential. Now since the diabetic body can transpose other 

 sugars into glucose, it must be able at least to dissociate the former 

 sugars deeply enough for this process. These transpositions are ac- 

 complished chiefly in the portal system and perhaps in other places 

 too, but certainly levulose and many other substances can be made in 

 the liver into glycogen, whose hydrolysis then yields glucose. 



The degree or character of the dissociation necessary for reciprocal 

 transformations differs from that which is a necessary prelude to de- 

 structive reactions such as oxidation. A very weak alkali suffices 

 in vitro for the former, while for the latter it is necessary to use a 

 somewhat stronger alkali concentration.^^ The diabetic body there- 

 fore behaves as though it were weakened with respect to the alkali 

 concentrations which it can bring to bear on sugars. 



As far back as 1871, Schultzen suggested that the error in diabetes 

 might be found in the disability of the body to dissociate the glucose 



"See Woodyatt, Jour. Biol. Cheni., 1915 (20), 129. 



