homeostasis/metabolism
• plasma insulin levels are increased at 2 min and 5 min of glucose challenge, but not at later 15 and 30 min time points
• mice fed a high-fat diet exhibit increased insulin secretion
• however, insulin sensitivity and insulin content remain unchanged and high-fat diet fed mice show unchanged intraperitoneal insulin tolerance test
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• mice stressed with low-dose streptozotocin (STZ) injections display a greater increase in blood glucose levels than treated controls
• mice fed a high-fat diet and treated with a single dose of STZ exhibit higher blood glucose levels
• however, random-fed blood glucose levels in high-fat diet fed mice are similar to controls
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• STZ-injected mice show a reduction in plasma insulin levels by about 40% after 18 days compared to controls
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• mice fed a normal diet show augmented glucose tolerance
• mice fed a high-fat diet for 12 weeks exhibit improved intraperitoneal glucose tolerance
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cellular
• mice treated with S961 for 3 days exhibit lower BrdU incorporation in beta cells, indicating a reduced proliferative capacity under oxidative/metabolic stress conditions
• mice show an approximate 2-fold increase in apoptosis in beta cells 3 days after the last STZ injection
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• mice show an approximate 2-fold increase in apoptosis in beta cells 3 days after the last STZ injection
• islets ex vivo treated with cytokines and interferon gamma show increased apoptosis of beta cells
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endocrine/exocrine glands
• STZ-injected mice show an approximate 2-fold lower beta cell mass after 18 days compared to controls
• mice fed a high-fat diet and treated with a single dose of STZ exhibit lower beta cell mass
• mice treated with the insulin receptor antagonist S961 for 3 days exhibit a lower pancreatic beta cell mass than controls
• however, beta cell mass and islet morphology are normal under basal conditions
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• STZ-injected mice show a reduction in total pancreatic insulin content by about 70% after 18 days compared to controls
• mice fed a high-fat diet and treated with a single dose of STZ exhibit lower total insulin content
• mice treated with S961 for 3 days exhibit lower BrdU incorporation in beta cells, indicating less proliferation under oxidative/metabolic stress conditions
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• mice show an approximate 2-fold increase in apoptosis in beta cells 3 days after the last STZ injection
• islets ex vivo treated with cytokines and interferon gamma show increased apoptosis of beta cells
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• plasma insulin levels are increased at 2 min and 5 min of glucose challenge, but not at later 15 and 30 min time points
• mice fed a high-fat diet exhibit increased insulin secretion
• however, insulin sensitivity and insulin content remain unchanged and high-fat diet fed mice show unchanged intraperitoneal insulin tolerance test
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growth/size/body
• STZ-injected mice show a decrease in body weight by about 20% after 18 days compared to controls
• however, body weight of high-fat diet fed mice is similar to controls
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