Analysis Tools
homeostasis/metabolism
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• mice show a defect in glucose-dependent insulin secretion that leads to early-onset, mild and moderately progressive diabetes
• mice subjected to hyperglycemic clamps require an approximate 50% lower rate of glucose infusion to maintain steady-state hyperglycemia
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• mice are impaired in secreting insulin in response to the ATP-dependent K-channel blocker, glibenclamide, and to the depolarizing agent, I-arginine
• beta cells exhibit reduced calcium-dependent insulin secretion
• purified islets show lower insulin secretion in response to the sulfonylurea glibenclamide, the PKC activator PMA, and the L-type Ca channel activator Bay-K8644
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• mice exhibit hyperglycemia in the fasted, refed, and random-fed states as early as 12 weeks of age
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• mice exhibit lower plasma insulin levels in fasted, refed, and random-fed states, although not significant in the latter state
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• mice show impaired glucose tolerance that worsens progressively with age during intraperitoneal glucose tolerance tests, without changes to peripheral insulin sensitivity
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endocrine/exocrine glands
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• as mice age to 12 months, beta cell dedifferentiation occurs
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• beta cells are metabolically inflexible such that they preferentially utilize lipids rather than carbohydrates as an energy source resulting in impaired ATP generation and reduced calcium-dependent insulin secretion
• glucose oxidation to carbon dioxide is impaired by about 50% in islets at most glucose concentrations
• palmitate oxidation by islets in the presence of basal glucose is 2-fold higher and nearly 2.5-fold higher in high glucose
• glycerolipid synthesis of islets is normal at low glucose concentrations but fails to increase at elevated glucose concentrations, resulting in lower conversion of palmitate into diacylglycerides and triglycerides indicating that beta cells appear to be locked in a lipid oxidative state
• membrane depolarization-induced calcium influx in response to rising glucose concentrations is lower in beta cells
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• mice are impaired in secreting insulin in response to the ATP-dependent K-channel blocker, glibenclamide, and to the depolarizing agent, I-arginine
• beta cells exhibit reduced calcium-dependent insulin secretion
• purified islets show lower insulin secretion in response to the sulfonylurea glibenclamide, the PKC activator PMA, and the L-type Ca channel activator Bay-K8644
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cellular
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• as mice age to 12 months, beta cell dedifferentiation occurs
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• islets show a decrease in glucose-induced oxygen consumption
• raising glucose levels does not increase ATP turnover in purified islets as in control 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:215526 | |
