Autoimmune response directed to pancreatic beta cells in rats induced by combined treatment with low doses of streptozotocin and complete Freund's adjuvant.

Despite the existence of circumstantial evidence, a direct proof of an autoimmune basis for beta cell destruction in human type I diabetes has not yet been obtained. The present study was designed to test on Wistar rats whether a low-dose streptozotocin (SZ) treatment in combination with complete Freund's adjuvant (CFA) could be a useful approach to induce an autoimmune response to beta cells. Rats were weekly injected i.p. either with CFA or with SZ alone or with both CFA and SZ. Only the SZ-CFA-treated rats developed severe hyperglycemia. In these animals the pancreatic insulin content was nearly completely depleted. Only in SZ-CFA-treated rats cytotoxic autoantibodies to islet cells were found. The results show that in this new model of type I diabetes autoimmune reactions are involved in the destruction of beta cells.