endocrine/exocrine glands
• 70% of mice show dysplastic islets with disorganized cells, irregular in shape and size
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• pancreatic beta cells are 5 times larger than wild-type cells
• beta cells have prominent nuclei with large nucleoli and are surrounded by dilated and asymmetric vessels
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• increase in beta cell mass by 3.5-fold
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• islet hypertrophy, as defined by large beta cells which maintain an organized structure with well-defined margins
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• mice develop pancreatic islet tumors in older age
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• 30% penetrance of insulinomas after 10 months of age
• insulinomas are classified as adenomas with rounded and encapsulated edges or multinodular adenomas with partial loss of the fibrous capsule
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• 4 of 19 tumor cases are invasive carcinomas
• one case of lung metastasis is seen
• in the pancreatic carcinoma and lung metastasis, Brd-U positive malignant tumor cells are negative for the transgene and insulin expression and negative for neuroendocrine markers
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• peripheral or infiltrating fibrosis is commonly seen in islets
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homeostasis/metabolism
hypoglycemia
(
J:144599
)
• hypoglycemia in the fed and fasted state
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• 2.6-fold higher insulin levels at 3 months of age
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• control of glycemia after injection of glucose is improved
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mortality/aging
• lethality is increased after 1 year of age; death is preceded by hypoglycemia
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neoplasm
• mice develop pancreatic islet tumors in older age
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• 30% penetrance of insulinomas after 10 months of age
• insulinomas are classified as adenomas with rounded and encapsulated edges or multinodular adenomas with partial loss of the fibrous capsule
|
• 4 of 19 tumor cases are invasive carcinomas
• one case of lung metastasis is seen
• in the pancreatic carcinoma and lung metastasis, Brd-U positive malignant tumor cells are negative for the transgene and insulin expression and negative for neuroendocrine markers
|