MECHANISMS IN HYPERGLYCEMIA AND HYPOGLYCEMIA 405 



Protein Synthesis 



The complexities which may be encountered with alloxan are well illus- 

 trated by the effects on tryptophan peroxidase levels in rat liver (Schor 

 et al, 1958; Schor and Frieden, 1958). It is known that tryptophan and 

 insulin induce the formation of liver tryptophan peroxidase. The admin- 

 istration of alloxan leads to a biphasic curve for the levels of this enzyme: 

 an initial peak around 6 hr (6-fold increase) is followed by a fall to normal 

 levels and then a second rise at 72 hr (8- to 10-fold increase). These fluc- 

 tuations are independent of blood glucose. The initial peak may be due 

 to the release of insulin or to an adrenal-mediated stress reaction, since 

 adrenalectomy abolishes this early peak, and the delayed peak may be 

 due to tryptophan liberated from cellular breakdown in certain tissues. 

 These effects are discussed here because superficial interpretation or limited 

 experimental data might lead one to conclude that alloxan directly affected 

 protein synthesis. It may, but these results can be explained otherwise. 

 There has been essentially no work indicating what alloxan may do to 

 protein synthesis. Berenbaum (1962) could find no depression of antibody 

 formation by alloxan at high doses in mice given vaccine, but this is not 

 a very good test for protein synthesis. It is interesting to note, in view 

 of the results discussed above, that alloxan inhibits the conversion of tryp- 

 tophan to kynurenine both in vitro and in vivo (Takagi et al., 1958). It 

 is not known whether the action is on tryptophan pyrrolase or on kynu- 

 renine formylase, but it might provide an additional mechanism for the 

 effects of alloxan on tryptophan peroxidase levels, inasmuch as increased 

 tryptophan levels might result from the inhibition. 



MECHANISMS INVOLVED IN THE EARLY HYPERGLYCEMIA 

 AND HYPOGLYCEMIA 



There have been several postulated mechanisms to explain the early 

 changes in blood glucose following the administration of alloxan, and these 

 have often revolved around the problem of whether the site of action is 

 pancreatic or extrapancreatic. Certainly the major site of action seems 

 now to be on the /5-cells and knowledge of the early changes may provide 

 a clue to the diabetogenic mechanism. 



Initial Hyperglycemia 



The rapidly developing hyperglycemia might most reasonably be due 

 to a suppression of glucose utilization by the tissues or to a release of glu- 

 cose from the tissues (particularly the liver) at a rate faster than its utili- 

 zation. It was suggested originally by Dunn et al. (1943 a) that the hyper- 

 glycemia may result from hepatic glucose release due to adrenal discharge 



