Abstract
Series of 7-wk male and female DBA/2 N mice were infected intraperitoneally with 0.5 ml of M variant of encephalomyocarditis (EMC) virus with a titer of TCID50, 103/0.1 ml.
Glucose tolerance tests in fasting mice were performed by intraperitoneal injection of glucose, 2 mg/g body weight. The fasting IRI concentrations of male mice were determined at 0, 3, 7, and 14 days after inoculation. Histological examinations with H-E staining were performed on pancreatic tissues of male mice at 3, 7, and 14 days after inoculation. The specific binding of 125I-insulin to insulin receptors was observed by radioreceptor assay using liver particulate membrane of fasting mice at 0, 1, 3, and 7 days after inoculation.
The fasting blood glucose of infected male mice remained normal at the 1st and 3rd day, but elevation of fasting blood glucose appeared at the 7th day and continued for 7-14 days after inoculation. Elevation of blood glucose after glucose load appeared at the 3rd day after inoculation and maximal blood glucose elevation was observed at the 7th day. The glucose intolerance continued for 5 months, although the severity of glucose intolerance showed a decline. The glucose intolerance of female mice remained milder than that of male mice at the same period.
Changes of fasting IRI concentrations in infected male mice were not observed at the 3rd and 7th day, but a remarkable decrease in IRI concentrations was observed at the 14th day.
Histological alterations of the islets of Langerhans became evident at the 3rd day. Disruption of the overall architecture of the insular tissue, degeneration and pyknosis of the insular cells, and proliferation of blood vessels were observed, but infiltration of mononuclear cells did not appear unitl the 14th day after inoculation.
The specific binding of 125I-insulin to insulin receptors of infected mice remained unchanged at the 1st day after inoculation, but was markedly decreased at the 3rd day. The binding returned to a normal control value at the 7th day in infected female mice. Scatchard analysis revealed that there was no change in the affinity constant of high affinity-low capacity component for 1-7 days after inoculation, but the affnity constant of low affinity-high capacity component was significantly decreased at the 3rd day and returned to a normal control value at the 7th day after inoculation. The numbers of insulin receptors in infected mice decreased slightly at the 1st day after inoculation, showed a minimum value at the 3rd day, and then returned to a normal control value at the 7th day.
It is considered that glucose intolerance at the early stage of virus-induced diabetes mellitus is due to impairment of insulin receptors, and that glucose intolerance at the late stage is due to hypoinsulinemia resulting from pancreatic damage.
