Induction of diabetes by cumulative environmental insults from viruses and chemicals

Abstract

Encephalomyocarditis virus (EMC) induces diabetes in certain inbred strains of mice by infecting and destroying pancreatic β cells^1,2, the severity of the diabetes depending on the number of β cells destroyed³. In strains of mice resistant to EMC-induced diabetes, insufficient β cells are damaged to alter glucose homeostasis^3,4. However, diabetes can be produced in many species by streptozotocin, a highly specific β-cell toxin⁵. Here, we used concentrations of streptozotocin that did not produce diabetes, but reduced the β-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 β-cell damage⁶, diabetes developed if the mice were first treated with sub-diabetogenic doses of streptozotocin. These findings suggest that diabetes may result from cumulative β-cell damage induced by sequential environmental insults.