Survival of intrasplenically implanted islets in mice with experimental insulitis and hyperglycemia.
Injections of repeated, subdiabetogenic doses of streptozotocin to C57BL/KsJ mice induced a slowly developing hyperglycemia and pancreatic insulitis similar to that observed in human type I diabetes. It was found that the hyperglycemia could be normalized in these animals by the intrasplenic implantation of syngeneic islets. This could be achieved both 9 and 14 days after the first streptozotocin injection. At the first time point there was a severe insulitis in the pancreas of the recipient. When animals that had been cured by an intrasplenic islet implant were given three subdiabetogenic booster-doses of streptozotocin, they reverted to hyperglycemia. This suggests that cell-mediated immune reactions are of etiologic significance in this diabetes model, since mice made diabetic by a single large dose of streptozotocin and subsequently cured by islet transplantation remained unaffected by the booster-dose administration of streptozotocin. To test the hypothesis that the beta-cell destruction induced by streptozotocin is the triggering mechanism for the insulitis process, syngeneic islets were implanted into the spleen after being exposed in vitro to a weak streptozotocin concentration. This treatment led to normoglycemia in only two of seven alloxan-diabetic recipients. Streptozotocin-treated islets implanted into normoglycemic recipients were recovered intact in the spleens, and pancreatic islet morphology was not influenced by this treatment. The present data do not speak against ongoing attempts to cure human diabetics with islet cell transplantation despite the fact that islet lesions that may reflect immunologic mechanisms are encountered in type I diabetes.
D000496:Alloxan; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000628:therapy*; D003922:Diabetes Mellitus, Type 1 / Q000628:therapy; D005260:Female; D006085:Graft Survival; D006943:Hyperglycemia / Q000139:chemically induced / Q000628:therapy*; D007249:Inflammation / Q000139:chemically induced; D007515:Islets of Langerhans / Q000187:drug effects / Q000473:pathology; D016381:Islets of Langerhans Transplantation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D013311:Streptozocin / Q000008:administration & dosage
D013311:Streptozocin; D000496:Alloxan