The role of thymic immunity and insulitis in the development of streptozocin-induced diabetes in mice.
This article is concerned with the role of thymic immunity in the development of diabetes experimentally induced by multiple injections of subdiabetogenic doses of streptozocin (STZ). Euthymic +/+, +/nu, and athymic nu/nu mice of CD-1 and BALB/cAJcl origin were studied. Daily intraperitoneal (i.p.) injections of 30 mg/kg body wt of STZ for 5 consecutive days in CD-1 +/+ and +/nu mice resulted in hyperglycemia and mononuclear cell infiltrations of islets (insulitis). The CD-1 nu/nu mice developed neither insulitis nor hyperglycemia after the same treatment. In the nu/nu mice, when thymic immunity was restored by thymus grafting, both insulitis and hyperglycemia developed, thus demonstrating that thymic immunity was a prerequisite for the development of insulitis and hyperglycemia. There was a positive correlation among the degrees of thymic immunity, insulitis, and hyperglycemia in CD-1 +/nu, nu/nu with thymus grafts, and nu/nu mice, indicating that thymic immunity may amplify the diabetogenic effect of STZ by eliciting insulitis. In contrast, in BALB/cAJcl mice, a nonsusceptible strain to insulitis, no significant differences in plasma glucose levels were observed between the +/nu and nu/nu or between the nu/nu and thymus-grafted nu/nu mice. Furthermore, no significant difference was found in plasma testosterone levels between the +/nu and nu/nu mice of both CD-1 and BALB/cAJcl origin. In conclusion, our data indicate that thymic immunity enhances the diabetogenic effect of STZ by eliciting insulitis in susceptible mice.
D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000276:immunology* / Q000473:pathology; D007111:Immunity, Cellular; D007515:Islets of Langerhans / Q000473:pathology*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008819:Mice, Nude; D013045:Species Specificity; D013311:Streptozocin / Q000633:toxicity; D013601:T-Lymphocytes / Q000276:immunology; D013739:Testosterone / Q000097:blood; D013950:Thymus Gland / Q000276:immunology* / Q000637:transplantation
D001786:Blood Glucose; D013739:Testosterone; D013311:Streptozocin