A murine model of insulin-dependent diabetes mellitus resulting from the cumulative effects of the nondiabetogenic strain of encephalomyocarditis virus and a single low dose of streptozocin.
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.
D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D003921:Diabetes Mellitus, Experimental / Q000209:etiology* / Q000382:microbiology; D003922:Diabetes Mellitus, Type 1 / Q000209:etiology* / Q000382:microbiology; D004195:Disease Models, Animal; D004686:Encephalomyocarditis virus; D004769:Enterovirus Infections / Q000150:complications*; D005260:Female; D005951:Glucose Tolerance Test; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D013311:Streptozocin / Q000008:administration & dosage; D013997:Time Factors
D001786:Blood Glucose; D013311:Streptozocin