Sensitivity of BB rat beta cells as determined by dose-responses to the cytotoxic effects of streptozotocin and alloxan.

BB rats of diabetes-prone lines develop a spontaneous Type 1 diabetic syndrome, with many immunological concomitants. No data are available as to the integrity of their islet beta cells prior to onset of the insulitis which proceeds to their selective destruction. We tested the effects of the beta-cytotoxins streptozotocin and alloxan on such rats, compared to Wistar and to non diabetes-prone BB control rats studied prior to usual age of diabetes onset. A dose-response of a single injection of the agents with respect to pancreatic insulin content 48 hr post-injection as well as to circulating insulin and glucose, weight, and lymphocyte counts was established. Clear dose-responses were found for pancreatic insulin content. Though less sensitive, plasma insulin and glucose values showed responses. Whereas some litters of diabetes-prone rats showed greater reductions of pancreatic insulin than controls after some doses of streptozotocin, overall results in 8-26 recipients of each dose showed no significant differences when compared with either BB or Wistar controls. With smaller numbers of diabetes-prone rats, the same was obtained for alloxan, though with fewer doses tested. The latter required the construction of an alloxan dose-response in normal Wistar rats. Thus, this study has not demonstrated a nonspecific increase in "fragility" of BB rat beta cells in response to these classical diabetogenic agents. This would be consistent with other data suggesting that the primary abnormality in the syndrome does not necessarily reside within the beta cell.