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- W3048494645 endingPage "115187" @default.
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- W3048494645 abstract "Prenatal exposure to dexamethasone (PDE) impairs pancreatic β cell development and glucose homeostasis in offspring especially females. To explore the underlying intrauterine programming mechanism, pregnant Wistar rats were subcutaneously administered with dexamethasone (0, 0.2 and 0.8 mg/kg·d) from gestational days (GD) 9 to 20. Female offspring were collected on GD20 (fetus) and in postnatal week 28 (adult), respectively. PDE reduced the serum insulin levels, β cell mass, and pancreatic insulin expressions in fetuses and adults, causing glucose intolerance after maturity. The persistent suppression of pancreatic angiotensin II receptor type 2 (AT2R) expression before and after birth could be observed in the PDE females, which is accompanied with decreased histone 3 lysine 14 acetylation (H3K14ac) and H3K27ac levels in AT2R promoter. PDE increased the gene expressions of glucocorticoid receptor (GR) and histone deacetylase 2 (HDAC2) in fetal pancreas. Furthermore, dexamethasone inhibited insulin biosynthesis while activated GR and HDAC2 expression in the rat INS-1 cells. The AT2R expression was repressed by dexamethasone in vitro but only H3K27ac levels in AT2R promoter were lowered. Dexamethasone enhanced the interaction between GR and HDAC2 proteins as well as the binding of GR/HDAC2 complex to AT2R promoter. Moreover, overexpression of AT2R could restore the suppressed insulin biosynthesis induced by dexamethasone in vitro, and both GR antagonist and histone deacetylase abolished the decreased H3K27ac level and gene expression of AT2R. In conclusion, continuous epigenetic repression of AT2R before and after birth may be involved in β cell dysfunction and glucose intolerance of the PDE adult female offspring." @default.
- W3048494645 created "2020-08-18" @default.
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- W3048494645 date "2020-10-01" @default.
- W3048494645 modified "2023-10-15" @default.
- W3048494645 title "Epigenetic repression of AT2 receptor is involved in β cell dysfunction and glucose intolerance of adult female offspring rats exposed to dexamethasone prenatally" @default.
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- W3048494645 doi "https://doi.org/10.1016/j.taap.2020.115187" @default.
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