endocrine/exocrine glands
• total islet glucagon content is 71% less than in controls
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• at 6 weeks of age alpha cells comprise only ~6% of islets compared to ~13% in wild-type controls at 6 weeks of age
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• significant alpha cell and islet hyperplasia at 7 months of age
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• modest increase in beta cell area, ~79% compared to ~71% in controls at 6 weeks of age
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• cultured islets secrete ~60% less glucagon compared to controls in response to low glucose and ~47% less in response to 10 mM arginine
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• when glucagon secretion is normalized to islet glucagon content islet cells hypersecrete glucagon in high glucose conditons
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homeostasis/metabolism
• significantly hypoglycemic throughout an insulin tolerance test at 6 weeks of age compared to similarly treated wild-type mice
• however, mice over 6 months of age are hyperglycemic throughout an insulin tolerance test
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• cultured islets secrete ~60% less glucagon compared to controls in response to low glucose and ~47% less in response to 10 mM arginine
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• when glucagon secretion is normalized to islet glucagon content islet cells hypersecrete glucagon in high glucose conditons
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• become significantly hypoglycemic following an overnight fast at 6 weeks of age
• however, by 3 and 6 months of age mice are no longer hypoglycemic following an overnight fast
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• 30 min after an insulin injection mice have a ~2.5 fold decrease in plasma glucagon relative to wild-type mice
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