Induction of diabetes by cumulative environmental insults from viruses and chemicals.

Encephalomyocarditis virus (EMC) induces diabetes in certain inbred strains of mice by infecting and destroying pancreatic beta cells, the severity of the diabetes depending on the number of beta cells destroyed. In strains of mice resistant to EMC-induced diabetes, insufficient beta cells are damaged to alter glucose homeostasis. However, diabetes can be produced in many species by streptozotocin, a highly specific beta-cell toxin. Here, we used concentrations of streptozotocin that did not produce diabetes, but reduced the beta-cell reserve. When strains of mice normally resistant to EMC-induced diabetes were first treated with sub-diabetogenic doses of streptozotocin, then infected with EMC virus, diabetes developed. Furthermore, when mice were infected with viruses such as Coxsackie B3 and B5, which ordinarily produce little if any beta-cell damage, diabetes developed if the mice were first treated with sub-diabetogenic doses of streptozotocin. These findings suggest that diabetes may result from cumulative beta-cell damage induced by sequential environmental insults.