Characterization of Insulin-Dependent Diabetes Mellitus Induced by a New Variant (DK-27) of Encephalomyocarditis Virus in DBA/2 Mice

Katsuaki Dan, Yoshiko Seto, Tomonobu Fujita, Haruhisa Fujita, Ryuichi Kato, Yoshiaki Asaba, Izumi Takei

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Abstract

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 infected with various infectious doses of DK-27 intraperitoneally. Blood glucose and insulin levels were examined in association with the viral replication. Pancreatic pathology and hormone contents and stable hemoglobin A1c (St-A1c) levels were also examined on the final day of observation (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, blood insulin levels elevated at 48 hr, promptly decreased, and subsequently became sustained hypoinsulinemia. Viral replication in pancreases reached the highest titers at 48 hr and rapidly disappeared with all infectious doses used. Pancreatic insulin contents in infected mice were not detectable, and glucagon contents were not affected. In pathological examination, atrophy of islets and marked diminution of B-cells were observed, and A-cells occupied the major part of an infected islet. 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.

Original languageEnglish
Pages (from-to)211-218
Number of pages8
JournalExperimental Animals
Volume44
Issue number3
DOIs
Publication statusPublished - 1995 Jan 1

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Keywords

  • DK-27 variant
  • diabetes animal model
  • encephalomyocarditis virus
  • insulin-dependent diabetes mellitus
  • stable hemoglobin A1c

ASJC Scopus subject areas

  • Animal Science and Zoology
  • Biochemistry, Genetics and Molecular Biology(all)
  • veterinary(all)

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