DIABETOGENIC ACTION 



385 



activity, and it has been postulated that this is perhaps due to the lack of 

 enolization (Hidy, 1946), but it could also be due to greater instability 

 and toxicity (Bernhard et al., 1947). Dialurate is diabetogenic since it 

 can be oxidized to alloxan in the body (Siliprandi and Pisati, 1949), but 

 if this is prevented by the administration of cysteine, it becomes inactive 

 (Lazarow et al., 1948). Alloxantin readily breaks down to alloxan and 

 hence is diabetogenic (Brada, 1949). Urate has been reported to produce 

 diabetes in massive doses under appropriate conditions, and metabolism 

 to alloxan has been thought to be responsible, but the present evidence 

 is against this. Some metal chelates of alloxan produce an initial hyper- 

 glycemia, but whether /5-cell destruction can occur is not known (Lange 

 and Foye, 1956). 



The following substances have been found to be nondiabetogenic: isatin, 

 ninhydrin, and benzoyleneurea (Hidy, 1946); alloxanate, barbiturate, mu- 

 rexide, mesoxalate, oxalurate, and parabanate (Jacobs, 1937); alloxantin, 

 murexide, isatin, and ninhydrin (Briickmann and Wertheimer, 1947); caf- 

 feine and phenoldialurate (Bernhard et al., 1947); violuric acid and uramil 

 (Briickmann and Wertheimer, 1945); and uridine (Lazarow, 1954 a). 



HN 





NOH jl /NHj 



HN Y 



H 



HN ^ 



H 



Barbituric 

 acid 



Violuric 

 acid 



Uramil 



Parabanic 

 acid 



,ri 



O" ~^N 

 H 



HN 



O-^N 



Ninhydrin 



Benzoyleneurea 



Briickmann and Wertheimer (1947) pointed out that the reactive por- 

 tion of the alloxan molecule seems to be the central hydrated carbonyl of 

 the — CO — C(0H)2 — CO — moiety, and that alteration of this abolishes 

 the diabetogenic activity. Dehydroascorbate possesses this grouping and is 

 somewhat diabetogenic. However, as discussed previously, it is not certain 

 that the 5-CO group is hydrated. Also, any change at the 5-position would 

 not only change its properties, but alter the rest of the molecule; e. g., the 

 quinonoid structure would become impossible. The inactivity of N, N'- 

 dimethylalloxan, which possesses the above grouping, is difficult to explain, 



