MECHANISM OF THE DIABETOGENIC ACTION 411 



it is doubtful if high or low levels of glutathione would make much dif- 

 ference. Furthermore, MacDonald (1959) found no significant difference in 

 the SH group contents of acinar and islet tissue, using Bennett's red SH 

 reagent. 



{E) The reducing power of jS-cells is relatively low. Alloxan is readily re- 

 duced to dialurate by various substances and certain dehydrogenase sys- 

 tems in the cell. If the reducing activity of the /3-cells were low, less al- 

 loxan would be converted to dialurate and would be free to act for a longer 

 time. Supravital staining of the pancreas with Janus green B and placing 

 the tissue under anaerobic conditions lead to bleaching of the dye in those 

 regions with the highest reducing activity, and Bensley (1911) had shown 

 that the bleaching rate in the islets is very slow. Since Janus green B is 

 reduced by NADH-flavoprotein systems and oxidized by the cytochromes, 

 the state of the dye roughly indicates the balance between oxidative and 

 reductive potencies in a cell. The results on islet tissue point to a low con- 

 centration of dehydrogenases and their coenzymes. Lazarow and Cooper- 

 stein (1951) took advantage of the separable islets of the toadfish and 

 demonstrated a relatively low level of succinate dehydrogenase. The ratio 

 of the dehydrogenase to cytochrome oxidase is low and if this is true 

 of other dehydrogenases, the alloxan ±^ dialurate equilibrium would be 

 shifted to the left, i. e., any dialurate formed would be rapidly reoxidized 

 to alloxan. Succinate dehydrogenase has also been shown to be lower in 

 islet tissue than in acinar tissue by the neotetrazolium technique (Barr- 

 nett, 1951). Lazarow and Cooperstein thus suggested that the effective 

 level of alloxan would remain higher for a longer time in islet tissue, and 

 that this might account for the selective action. It must be mentioned 

 that certain other tissues, e. g. the gonads, exhibit a similar reducing 

 deficiency and are not susceptible to alloxan. One again wonders if this 

 effect could be sufficiently great to prolong the alloxan concentration sig- 

 nificantly, inasmuch as other pathways of alloxan inactivation are quite 

 active. 



(F) The P-cells contain a low concentration of some vital enzyme or cof actor. 

 The effects of pseudoirreversible or titration inhibitors depend on the 

 relative amounts of the component attacked in the different tissues (page 

 1-78). Ackermann and Potter (1949) suggested that the selective damage 

 to the /?-cells by alloxan might be an example of this, the /?-cells containing 

 a smaller amount of some SH component with which alloxan reacts. La- 

 zarow (1954 a) has also considered the possibility that the /?-cells contain 

 a low level of some thiol (such as glutathione or coenzyme A), the inactiva- 

 tion of which would impair glyceraldehyde-3-P dehydrogenase or certain 

 transacetylations, or of some SH enzyme with which alloxan readily reacts. 

 It is, of course, not only a matter of the level of some critical substance, 



