homeostasis/metabolism
• in doxycycline-treated mice there is an increase in glucagons-positive cells
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• there is a marked reduction in insulin in pancreata of doxycycline-treated mice; after withdrawal of doxycycline, insulin +ve cells are detected in islets of smaller islet-like cell clusters
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• 14 days after doxycycline withdrawal after 14 days of treatment resulted in a significant decrease in blood glucose levels with 4/5 mice becoming normoglycemic by 28 days
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• with doxycycline treatment for 21 day, adult rescue mice show a 4-fold increase in fasting blood glucose to diabetic levels
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• adult transgenic rescue animals treated with doxycycline for 14 days exhibit a defective response to glucose challenge compared to wild-type, non mutant transgenic, or untreated rescue mice
(J:79206)
• when adult mice are treated with doxycycline for 0, 7, 14, or 21 days, mice show an increased early glucose response within 7 days of start of treatment and ability to recover from glucose challenge is impaired compared to untreated transgenics where glucose levels recover to basal levels within 3 hours; by 14 days of doxycycline treatment, mice have diabetes
(J:101742)
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endocrine/exocrine glands
• after 14 or 28 days of dox treatment there are, still present, beta cells which lack insulin
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• after dox treatment for 14 days, there is a significant decrease in islet area compared to wild-type
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• pancreas of transgenic rescue newborn mice is 50% the size of a normal wild-type neonatal pancreas
• treatment of pregnant mice with doxycycline from the first day of pregnancy through parturition prevents formation of the pancreas in mice with the transgenic rescue genotype
• treatment on E11.5 arrests pancreatic development ~36 hours later; at birth the underdeveloped remnant consisted of a large and extended duct with several terminal, aborted, ductal buds with ducts lined with a single layer of primitive epithelial cells and with no acinar or islet tissue
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• in doxycycline-treated mice there is an increase in glucagons-positive cells
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• there is a marked reduction in insulin in pancreata of doxycycline-treated mice; after withdrawal of doxycycline, insulin +ve cells are detected in islets of smaller islet-like cell clusters
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cellular
• foci of duct proliferation are present in mice after 14 days of doxycycline treatment and become more prominent with continued treatment
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