endocrine/exocrine glands
• after high-fat diet (HFD) feeding for 20 weeks, mean beta cell mass is ~2-fold smaller than that in HFD-fed wild-type controls
• however, no differences in beta cell mass are observed in untreated mice
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• after HFD treatment, mean pancreatic islet mass is ~2-fold smaller than that in HFD-fed wild-type controls
• however, no differences in pancreatic islet mass are observed in untreated mice
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• under untreated conditions, a significantly higher % of beta cells stain positive for the ER stress markers Hspa5 and Dnajc3 than in wild-type islets, indicating a basal islet defect
• however, no differences in the expression of these stress markers are observed after HFD treatment
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• after HFD treatment, the proliferative index of beta cells is significantly lower than that in HFD-fed wild-type controls, as shown by Ki67 staining
• after treatment with streptozotocin (STZ, a beta cell-specific toxin), the number of proliferating beta cells is significantly lower than that in STZ-treated wild-type islets, as shown by insulin and BrdU staining
• no differences in beta cell proliferation are observed in untreated mice
• apoptosis levels are similar to those in wild-type controls under untreated or HFD-treated conditions
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• upon glucose challenge, HFD-fed mice show a lower level of insulin release than HFD-fed wild-type controls in glucose tolerance tests
• however, insulin sensitivity is normal after HFD treatment in insulin tolerance tests
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homeostasis/metabolism
• upon glucose challenge, HFD-fed mice show a lower level of insulin release than HFD-fed wild-type controls in glucose tolerance tests
• however, insulin sensitivity is normal after HFD treatment in insulin tolerance tests
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• after HFD treatment, mice show significantly lower fed blood insulin levels than HFD-fed wild-type controls
• however, blood glucose and body weight remain normal after HFD treatment
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• under untreated conditions, very long chain ceramide species containing C26 and C26:1 fatty acids are significantly reduced in pancreatic islets relative to those in wild-type islets
• however, circulating sphingolipid profiles are normal in the plasma
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cellular
• after HFD treatment, the proliferative index of beta cells is significantly lower than that in HFD-fed wild-type controls, as shown by Ki67 staining
• after treatment with streptozotocin (STZ, a beta cell-specific toxin), the number of proliferating beta cells is significantly lower than that in STZ-treated wild-type islets, as shown by insulin and BrdU staining
• no differences in beta cell proliferation are observed in untreated mice
• apoptosis levels are similar to those in wild-type controls under untreated or HFD-treated conditions
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• under untreated (basal) conditions, a significantly higher % of pancreatic beta cells stain positive for the ER stress markers Hspa5 and Dnajc3 than in wild-type islets, indicating increased beta cell ER stress
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integument
N |
• mice show no apparent skin defects at P4 or during adulthood
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