CHARACTERIZATION OF INSULIN-DEPENDENT DIABETES-MELLITUS INDUCED BY A NEW VARIANT (DK-27) OF ENCEPHALOMYOCARDITIS VIRUS IN DBA 2 MICE/

A murine diabetes mellitus induced with a new diabetogenic variant (DK -27) which we isolated from the M variant of the encephalomyocarditis (EMC) virus was characterized. Male DBA/2 mice (9.5 weeks old) were in fected with various infectious doses of DK-27 intraperitoneally. Blood glucose and insulin levels were examined in association with the vira l replication. Pancreatic pathology and hormone contents and stable he moglobin A1c (St-A1c) levels were also examined on the final day of ob servation (35 days of post-infection). in infected mice, blood glucose levels rapidly elevated at 72 hr, slightly decreased between 7 and 10 days and finally became sustained hyperglycemia. On the other hand, b lood insulin levels elevated at 48 hr, promptly decreased, and subsequ ently became sustained hypoinsulinemia. Viral replication in pancrease s reached the highest titers at 48 hr and rapidly disappeared with all infectious doses used. Pancreatic insulin contents in infected mice w ere not detectable, and glucagon contents were not affected In patholo gical examination, atrophy of islets and marked diminution of B-cells were observed, and A-cells occupied the major part of an infected isle t. St-A1c levels reflected lasting hyperglycemia. These findings show that DK-27 causes insulin-dependent diabetes mellitus by the specific and direct destruction of pancreatic B-cells in susceptible mice. Such a diabetic model mouse will be useful for therapeutic studies.