FATE OF ALLOXAN IN ANIMALS 393 



that alloxan is rapidly broken down to alloxanate in blood and hence one 

 should perhaps analyze for the latter to detect if alloxan is produced in 

 the tissues. Hydrolysis of alloxanate gives oxomalonate and this can be 

 detected as a dinitrophenylhydrazone. Alloxanate was found in the urine 

 of normals and diabetics, but the levels were not stated. 



Schieler (1948) administered glucose orally to fasted rats and found the 

 blood alloxan to be increased some 50-fold to around 0.07 mM. This could 

 not be confirmed in rats by Huisman et al. (1950) or in the dog and man 

 by Sobotka and Luisada-Opper (1954). However, Loubatieres and Bou- 

 yard (1951 a, b) found a similar 50-fold increase when the glucose is given 

 orally, but essentially no effect when the glucose is injected parenterally. 

 They believe that alloxan arises in the intestine and depends on glucose 

 absorption, since isolated intestine releases alloxan when treated with glu- 

 cose, Hyperalloxanemia was claimed to occur in experimental diabetes, 

 due to the elevated glucose levels, and it was suggested that diabetes might 

 occasionally be produced by release of alloxan during periods of hyper- 

 glycemia (Loubatieres, 1954). 



The interesting problem of the possible role of alloxan in the genesis 

 of diabetes has thus not been settled. It is conceivable that a disturbance 

 in purine metabolism in the /5-cells could lead to a localized high concen- 

 tration of alloxan, but this would be very difficult to detect. 



FATE OF ALLOXAN IN ANIMALS 



Alloxan is unstable in aqueous solutions and even more so in the pres- 

 ence of tissues or when injected into animals. Any direct effects of al- 

 loxan must therefore be exerted rapidly. Early work showed that alloxan 

 is metabolized completely in the body, alloxanate, alloxantin, parabanate, 

 and the red murexide appearing in the urine (Koehme, 1894; Lusini, 1894; 

 Cerecedo, 1931), and that application of high concentrations of alloxan to 

 various tissues leads to a red color, due presumably to murexide (Labes 

 and Freisburger, 1930; Lieben and Edel, 1932, 1933). We have seen that 

 alloxan is rapidly destroyed in blood and so it is not surprising that in- 

 travenously injected alloxan disappears from the blood within 3-5 min 

 (Leech and Bailey, 1945; Veksler, 1956). It has thus been concluded that 

 the effect of alloxan on the /?-cells must occur within 5 min after injection. 

 Some of the alloxan is converted to alloxanate (Paley et al., 1953) but 

 an appreciable fraction must be reduced to dialurate, which could be 

 reoxidized to alloxan in certain tissues, possibly by the cytochrome system. 

 The level of alloxan in a tissue might then be determined in part by the 

 balance between oxidizing and reducing potencies. The results of Siliprandi 

 (1948) are somewhat different from those obtained by other workers 

 (Fig. 4-4), in that a much slower loss in the blood was observed. It is also 



