Analysis Tools
cellular
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• isolated heterozygous islets are significantly more susceptible to apoptosis at basal glucose concentrations than wild-type islets
• however, no significant differences are noted at high glucose (25 mM) or Ca2+ stress
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• dispersed beta cells are significantly more susceptible to apoptosis at basal glucose concentrations than wild-type islets
• however, no significant differences are noted at high glucose (25 mM) or Ca2+ stress
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endocrine/exocrine glands
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• isolated heterozygous islets are significantly more susceptible to apoptosis at basal glucose concentrations than wild-type islets
• however, no significant differences are noted at high glucose (25 mM) or Ca2+ stress
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• dispersed beta cells are significantly more susceptible to apoptosis at basal glucose concentrations than wild-type islets
• however, no significant differences are noted at high glucose (25 mM) or Ca2+ stress
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• islet isolation procedures generate very few islets (always <100) from heterozygotes compared with wild-type mice (almost always >200 islets)
• isolated heterozygous islets appear fragmented and slightly smaller than wild-type
• in vivo, heterozygotes show a striking disruption of islet architecture and expansion of islet microvasculature at 3 months; however, even at 12 months, some heterozygous islets show no signs of damage or apoptosis
• in heterozygotes, islet number fails to increase with age and is ~50% less than wild-type by 12 months
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• in heterozygotes, beta cell mass fails to increase with age and is ~50% less than wild-type by 12 months
• reduced beta cell mass is mirrored by a lower pancreatic insulin content in older mice and can be explained by a reduced number of functional islets, rather than a reduction in insulin stored in single beta cells
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• perfused pancreata from heterozygous males display attenuated first-phase insulin secretion in response to a stepwise increase in glucose concentration from 5 mM to 20 mM glucose
• mutant pancreata show a reduced insulin release in response to 20 mM KCl; in the continued presence of 26 mM glucose, the large response to 20 mM arginine is also reduced
• insulin secretion in perfusion or static incubation experiments in response to glucose and other secretagogues is similar in islets isolated from heterozygous mutants compared with wild-type littermates
• glucose sensing and islet Ca2+ responses are normal in large, intact heterozygous mutant islets
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• at 12 months, older heterozygotes exhibit infiltration of lymphocytes (some TUNEL-positive) within or around islets
• immunofluorescent localization of Ki67 nuclear antigen indicates proliferation of lymphocytes within these islets
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homeostasis/metabolism
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• perfused pancreata from heterozygous males display attenuated first-phase insulin secretion in response to a stepwise increase in glucose concentration from 5 mM to 20 mM glucose
• mutant pancreata show a reduced insulin release in response to 20 mM KCl; in the continued presence of 26 mM glucose, the large response to 20 mM arginine is also reduced
• insulin secretion in perfusion or static incubation experiments in response to glucose and other secretagogues is similar in islets isolated from heterozygous mutants compared with wild-type littermates
• glucose sensing and islet Ca2+ responses are normal in large, intact heterozygous mutant islets
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• heterozygous mutant males exhibit significantly elevated blood glucose concentrations relative to wild-type males
• notably, heterozygous females display an attenuated increase in blood glucose levels relative to wild-type
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• heterozygotes exhibit a decline in glucose tolerance with increasing age
(J:82969)
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immune system
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• at 12 months, older heterozygotes exhibit infiltration of lymphocytes (some TUNEL-positive) within or around islets
• immunofluorescent localization of Ki67 nuclear antigen indicates proliferation of lymphocytes within these islets
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| maturity-onset diabetes of the young | DOID:0050524 |
OMIM:606391 |
J:48516 , J:82969 | |
| maturity-onset diabetes of the young type 4 | DOID:0111103 |
OMIM:606392 |
J:82969 | |
