endocrine/exocrine glands
• by 4 weeks after birth, few insulin positive beta-cells are present in pancreata
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• function is impaired as indicated by lower circulating insulin levels
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• islets in pancreata of diabetic mice contain CD8+ and CD4+ T cells, B-cells, and macrophages at 3 weeks
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homeostasis/metabolism
• after postnatal day 10, mice begin to develop elevated blood sugar level compare to controls
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• by 3 weeks of age, both males and females exhibit severe hyperglycemia
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• levels are significantly lower at 3 weeks compared to controls
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immune system
• mice show impaired immune tolerance towards insulin; tolerance towards other autoantigens is unimpaired
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• islets in pancreata of diabetic mice contain CD8+ and CD4+ T cells, B-cells, and macrophages at 3 weeks
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• upon stimulation with insulin, interferon-gamma secreting T cells are detected;
• pancreata of nude mice that received transplants of thymi from diabetic mutants display insulitis with T cell infiltrates at 16 weeks after transplantation
• Rag1 mice that received transfer of splenocytes from diabetic mutants show elevated blood glucose at 1-2 weeks after transfer with autoreactive T cells detected; at 4 weeks after transfer of CD4+ or CD8+ T cells, pancreata of Rag1 mice show insulitis and beta-cell destruction
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• insulin-stimulated T cells show high production of interferon-gamma
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• levels of anti-insulin autoantibodies in sera of 3-8 week old mice are significantly higher than in controls
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hematopoietic system
• upon stimulation with insulin, interferon-gamma secreting T cells are detected;
• pancreata of nude mice that received transplants of thymi from diabetic mutants display insulitis with T cell infiltrates at 16 weeks after transplantation
• Rag1 mice that received transfer of splenocytes from diabetic mutants show elevated blood glucose at 1-2 weeks after transfer with autoreactive T cells detected; at 4 weeks after transfer of CD4+ or CD8+ T cells, pancreata of Rag1 mice show insulitis and beta-cell destruction
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