Analysis Tools
homeostasis/metabolism
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• mice exhibit a phenotype changing from neonatal hypoglycemia with hyperinsulinemia to adult hyperglycemia with insulin deficiency and diabetes
• normal insulin sensitivity of peripheral tissues at 3 and 30 weeks of age, as determined by insulin tolerance testing (ITT)
• normal body weight and food intake at all tested ages
• normal serum GLP-1 or glucagon levels at 3 and 30 weeks of age
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• mice exhibit a phenotype changing from insulin hypersecretion at 3 weeks of age to insulin hyposecretion at 30 weeks of age
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• reduced first- and second-phase insulin secretory responses to glucose in intraperitoneal insulin releasing testing (IPIRT, 3 g glucose/kg bw) in young adult mice at 14 weeks of age
• reduced insulin secretion in response to high glucose stimulation at 30 weeks of age
• reduced total pancreas insulin content at 30 weeks of age
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• high insulin secretion in response to high glucose stimulation at 3 weeks of age
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• trend towards higher fasting plasma glucose levels in young adult mice at 14 weeks of age relative to age-matched wild-type controls
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• random plasma glucose levels are low in neonatal mice relative to age-matched wild-type controls
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• reduced plasma insulin levels in young adult mice at 14 weeks of age relative to age-matched wild-type controls
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• trend towards higher plasma insulin levels in neonatal mice relative to age-matched wild-type controls
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• increased blood glucose levels and area under the curve (AUC) during intraperitoneal glucose tolerance testing (IPGTT, 3 g glucose/kg body weight) in young adult mice at 14 weeks of age
• increased blood glucose levels and AUC during IPGTT (2 g glucose/kg body weight) at 12, 16, and 28 weeks of age, with no significant changes in AUC at 3 or 8 weeks of age
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• increased basal intracellular calcium ion concentration in young pancreatic beta cells at 3 weeks of age
• blunted intracellular calcium ion concentration in beta cells following glucose stimulation at 30 weeks of age
• chronic elevation of intracellular calcium causes beta cell loss and hypoinsulinemia
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endocrine/exocrine glands
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• increased apoptosis of islet cells at 30 weeks of age
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• acridine orange/propidium iodide (AO/PI) staining revealed an increase in dead pancreatic islet cells at 30 weeks of age
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• immunocytochemistry analysis revealed a significant increase in glucagon-staining cells within the core of the islets at 30 weeks of age
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• islet beta cell mass is significantly decreased at 30 weeks of age
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• immunocytochemistry analysis revealed a significant reduction in insulin staining and beta cell area of islets at 30 weeks of age
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• in primary pancreatic beta cells, the voltage-dependent K+ (Kv) channel current is significantly decreased while duration of the action potential is prolonged
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• mice exhibit a phenotype changing from insulin hypersecretion at 3 weeks of age to insulin hyposecretion at 30 weeks of age
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• reduced first- and second-phase insulin secretory responses to glucose in intraperitoneal insulin releasing testing (IPIRT, 3 g glucose/kg bw) in young adult mice at 14 weeks of age
• reduced insulin secretion in response to high glucose stimulation at 30 weeks of age
• reduced total pancreas insulin content at 30 weeks of age
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• high insulin secretion in response to high glucose stimulation at 3 weeks of age
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nervous system
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• although the magnitude of action potential evoked by a 0.5 nA current is normal, the duration of action potential, esp. the repolarization time, is prolonged in primary pancreatic beta cells
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• in primary pancreatic beta cells, the voltage-dependent K+ (Kv) channel current is significantly decreased relative to that in wild-type controls
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cellular
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• increased apoptosis of islet cells at 30 weeks of age
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• acridine orange/propidium iodide (AO/PI) staining revealed an increase in dead pancreatic islet cells at 30 weeks of age
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• CHOP immunohistochemistry revealed increased ER stress in pancreatic islet cells at 30 weeks of age
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| glucose metabolism disease | DOID:4194 | J:271003 | ||
