Differential Susceptibility of BALB/c Sublines to Diabetes Induction by Multi-Dose Streptozotocin Treatment

Abstract

Streptozotocin (SZ), an antibiotic isolated from Streptomyces acromogenes, has potent diabetogenic activity in mice. Chemically, Sz consists of 2-deoxy-D-glucose coupled at the second carbon to a N-nitrosomethylurea side chain; targeting of this toxin to the pancreatic beta (β) cells probably is a function of the glucose ring whereas the cell damage is likely mediated via the alkylating activity of the N-nitroso moeity (Wilson et al. 1983). When Sz is administered at doses between 150–300 mg per kg body weight in a single bolus (either i.p. or i.v.), males and females of most inbred strains of mice will develop an insulin-dependent diabetic state within 72 hours post-injection. The diabetes is primarily the consequence of direct Sz-mediated cytotoxicity to the β-cells, and the ensuing hyperglycemia is permanent. Although mice made diabetic by a single high dose of Sz are often used as a model for juvenile onset (insulin-dependent) diabetes, the model is compromised because Sz also exerts direct toxic effects on the liver, kidneys, and on cells of the immune sytem, a fact which complicates analysis of the insulin deficient state.