Non-obese diabetic (NOD) mice spontaneously develop an autoimmune diabetes with higher incidence in females than in males. In order to elucidate possible factors involved in the different incidence of diabetes between male and female mice, we studied the progression of pancreatic beta-cell loss in relation to mononuclear cell infiltration of the pancreas (insulitis). We examined the pancreas of 76 NOD mice (39 males and 37 females) of different ages. The beta-cell content was assessed by immunoperoxidase staining of sections with an anti-insulin serum and the severity of insulitis was determined by haematoxylin staining of the same sections. A semi-quantitative criterion was used to grade both parameters. The results showed that females have a faster loss of beta-cell mass, which progressively decreases with the increase of severity of insulitis. In males, a medium to severe degree of insulitis is required before initial loss of beta cells occurs. Under the age of 10 weeks there was a significantly lower content of beta cells in females than males (2.84 +/- 0.03 vs 2.67 +/- 0.07; P = 0.02). Since we never observed a significant difference in the degree of mononuclear cell infiltration in age-matched males and females, these data support the hypothesis of weaker beta-cell resistance to immunological attack in female mice. Thus beta-cell sensitivity, in addition to immunological activity, is an important factor in the pathogenesis of insulin dependent diabetes.
The non-obese diabetic (NOD) mouse is widely used to study the pathogenesis of insulin-dependent diabetes mellitus. However, the mechanisms responsible for beta-cell destruction, in this model, are still poorly defined. The CD95/CD95L system among other effector systems has been implicated in beta-cell death. In this study we investigated in NOD, non- obese resistant (NOR) and Balb/c mice the expression of CD95 and CD95L in alpha and beta pancreatic cells by immunohistochemistry and immunofluorescence. We demonstrate that alpha cells in the islets of Langherans constitutively express CD95L forming a natural shield around beta cells
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