Analysis Tools
growth/size/body
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• at >12 months of age, homozygotes of both sexes weigh ~20% more than wild-type controls
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• at >12 months of age, homozygotes show a small increase in body length relative to wild-type controls
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• at >3 months of age, both male and female homozygotes gain weight more rapidly than wild-type controls
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adipose tissue
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• at >12 months of age, homozygotes show a ~4-fold increase in abdominal adipose tissue relative to wild-type controls
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• at >12 months of age, homozygotes of both sexes display increased fat deposits around the heart and massive deposits of abdominal fat
• increased fat deposition is likely to be due to impaired blood glucose utilization in skeletal muscle
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homeostasis/metabolism
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• at 11 months, of age, fasted homozygotes of both sexes exhibit ~40% higher blood glucose levels at all times tested after a glucose challenge relative to similarly treated wild-type controls, and blood glucose returns to baseline levels at a much slower rate than in wild-type controls
• however, at 11 months of age, homozygotes of both sexes display normal fasting blood glucose levels relative to wild-type controls
• neither male nor female homozygotes display glucose intolerance at 6-8 months of age
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• after a 16-hr overnight fast, glycogen levels in skeletal muscle are reduced to ~10% of wild-type controls
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• at >11 months of age, homozygotes develop insulin resistance in skeletal muscle
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• basal glycogen synthase (GS) activity, presented as a ratio of GS activity in the absence of G-6P divided by the total activity in the presence of G-6P, is equal to only 0.1 in mutant skeletal muscle relative to 0.3 in wild-type controls
• insulin-stimulated GS activity in mutant skeletal muscle is increased by 1.5- to 2-fold, but fails to even approach the basal levels observed in wild-type controls, rising only to 0.2
• both basal and insulin-stimulated phopshorylase activity, presented as a ratio of phosphorylase activity in the absence of AMP divided by the total activity in the presence of AMP, is increased in mutant skeletal muscle relative to wild-type controls
• total levels of both phosphorylase and GS activity are reduced by 40-50% in mutant skeletal muscle relative to wild-type controls
• basal activity of PP1-R5/PTG, another glycogen targeted form of protein phosphatase 1 (PP1), is decreased in mutant skeletal muscle relative to that in wild-type controls
• insulin-stimulated PP1-R5/PTG activity is doubled in mutant skeletal muscle but not significantly altered in wild-type skeletal muscle
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muscle
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• at >12 months of age, basal uptake of 2-deoxy-d-[1,2-3H]-glucose (2-DOG) into skeletal muscle is reduced by 69% relative to wild-type controls during a glucose tolerance test
• in contrast, glucose transport into adipose tissue, glycogen levels, and glycogen synthase activity in adipose tissue remain normal
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• after a 16-hr overnight fast, glycogen levels in skeletal muscle are reduced to ~10% of wild-type controls
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cellular
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• at >12 months of age, basal uptake of 2-deoxy-d-[1,2-3H]-glucose (2-DOG) into skeletal muscle is reduced by 69% relative to wild-type controls during a glucose tolerance test
• in contrast, glucose transport into adipose tissue, glycogen levels, and glycogen synthase activity in adipose tissue remain normal
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| type 2 diabetes mellitus | DOID:9352 |
OMIM:125853 OMIM:601283 OMIM:601407 OMIM:603694 OMIM:608036 |
J:82422 | |
