Responses of pancreatic b cells to alloxan and streptozotocin in the guinea pig.

Guinea pigs injected with streptozotocin were significantly hyperglycemic on day 1 after injection but only mildly so on day 14. However, serum insulin levels were significantly depressed on day 14; at this time the animals had lost 25% of their initial body weights and were severely glycosuric. The volume fraction of immunostainable B cells in the pancreas was reduced to one third of control values by day 1 after injection and remained at this level by day 14. Animals that received alloxan were slightly hyperglycemic on day 1 but not day 14. Both serum insulin and volume fraction of B cells in the pancreas were reduced by 70% on day 1 but had returned to control levels by day 14. Body weights for this group were equivalent to controls at both time points. These data indicate that: streptozotocin treatment of guinea pigs causes a diabetes-like condition characterized by insulin deficiency, pancreatic B cell loss, glycosuria, and weight loss, which are not reversed in the first 2 weeks after injection, whereas hyperglycemia is only transitory; alloxan also produces a diabetes-like condition early after injection, but all signs of diabetes disappear within 2 weeks, by which time serum insulin levels and the volume fraction of B cells in the pancreas have returned to normal. The experimental results suggest that regeneration of islet B cells following destruction by alloxan may be the primary cause of the recovery of alloxan-injected guinea pigs from the effects of the drug, whereas the persistence of insulin deficiency is consistent with an absence of islet B cell regeneration in the streptozotocin-treated animals.