Islet implantation into diabetic mice with pancreatic insulitis.

Repeated injections of small doses of streptozotocin (s.z.) lead to a slowly-developing hyperglycemia with a concomitant infiltration of lymphocytes into the pancreatic islets. Similarly, intrasplenically islet-implanted but otherwise normal mice became diabetic when given the multi-s.z.-treatment, suggesting that the splenic location of the islets does not protect them from the toxic effects of s.z. or immune-reactions. Intrasplenic, syngeneic islet implantation normalized the elevated blood sugars of multi-s.z.-treated mice, irrespective of whether the transplantation was performed 8 or 15 days after the first injection of s.z. These findings suggest that s.z. has to be present in order to trigger the auto-immune process of this insulitis model. In support of this suggestion, we observed that hyperglycemic, multi-s.z.-treated mice cured by islet implantation reverted to a hyperglycemic state when treated repeatedly with small doses of s.z., suggesting the presence of a booster-dose phenomenon.