Key result
Combined EMC-B virus and low-dose streptozocin induces diabetes in male but not female mice.
The combination of EMC-B virus and low-dose streptozocin induces insulin-dependent diabetes in male mice, with the timing of insults playing a critical role likely mediated by virus-induced interferon.
Indicates male-specific vulnerability to sequential viral-toxin exposure in mice; leaves open relevance to human diabetes triggers.
The induction of insulin-dependent diabetes in outbred male and female mice was examined using a combination of the usually nondiabetogenic B-variant of encephalomyocarditis (EMC-B) virus and single low doses of streptozocin (STZ). Neither EMC-B virus nor low doses of STZ were overtly diabetogenic when administered alone; however, when these two insults occurred 1 day apart, diabetes resulted in male but not in female mice. The induction of diabetes was dependent on the time interval between these two insults, since EMC-B virus and STZ given 4 days apart did not induce diabetes. Unexpectedly, when the order of these two insults was reversed, diabetes occurred. The absence of diabetes when EMC-B virus was given before STZ suggested the possibility that virus-induced interferon blocked the cytotoxic effects of STZ. This suggestion was supported by the observation that an antiserum against beta interferon abrogated the virus-mediated protection against STZ-mediated cytotoxicity. Also, Poly I:C administered before a single diabetogenic dose of STZ delayed the onset of severe hyperglycemia.
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Blay et al. (1985) studied Insulin-dependent diabetes mellitus. Combination of EMC-B virus and streptozocin vs. EMC-B virus alone or streptozocin alone was evaluated on Induction of diabetes. A combination of EMC-B virus and a single low dose of streptozocin administered 1 day apart induced diabetes in male but not female mice, whereas neither agent alone was overtly diabetogenic.
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