mortality/aging
• increased spontaneous death observed at 6 weeks of age in males and at 10 weeks of age in females
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growth/size/body
• weight gain begins to lag relative to that of wild-type mice after 6 weeks of age
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homeostasis/metabolism
hypoglycemia
(
J:71840
)
• at 10-12 weeks of age, fasted homozygotes show a small but significant reduction of serum glucose levels relative to wild-type mice
• however, no significant differences are noted in fasted serum electrolytes at 6-8 weeks of age or in fed or fasting serum insulin levels and fed or fasting serum triglyceride levels at 10-12 weeks of age relative to wild-type mice
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• in response to i.p. injection of glucose (2 g/kg), homozygotes display a significantly improved glucose tolerance curve, with peak serum glucose levels of ~250 mg/dl at 30 min post-injection relative to 420 mg/dl in wild-type mice
• during in vivo hyperinsulinemic euglycemic clamp studies, homozygotes require a higher glucose infusion rate to maintain target serum glucose levels than wild-type mice
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• in response to 0.5 U/kg of insulin challenge, homozygotes exhibit a more rapid and sustained decrease in serum glucose than wild-type mice, with 50% of mutants either succumbing to hypoglycemia or requiring glucose injections to restore glucose levels
• increased insulin action is intrinsic to skeletal muscle, as shown by a 59% increase in in vitro insulin-stimulated glucose uptake into the soleus muscle
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muscle
• following incubation with insulin, male homozygotes show a 1.5-fold increase in in vitro glucose uptake into skeletal (soleus) muscle relative to wild-type males
• however, in the absence of insulin, in vitro glucose uptake into mutant skeletal muscle is similar to that in wild-type, indicating normal basal glucose transport
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cellular
• following incubation with insulin, male homozygotes show a 1.5-fold increase in in vitro glucose uptake into skeletal (soleus) muscle relative to wild-type males
• however, in the absence of insulin, in vitro glucose uptake into mutant skeletal muscle is similar to that in wild-type, indicating normal basal glucose transport
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