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NR1H2 & NR1H3 regulate gene expression linked to gluconeogenesis

Reactome ID: R-HSA-9632974

中文名称

NR1H2 和 NR1H3 调节与糖异生相关的基因表达

通路描述

肝 X 受体α (LXRα, NR1H3) 的激活改变肝脏和脂肪组织中基因的表达,这些基因共同可能限制肝脏葡萄糖输出并改善外周葡萄糖摄取。
在肝脏中,NR1H3 的激活导致参与糖异生基因表达抑制,包括葡萄糖 -6-磷酸酶 (G6Pase) 和磷酸烯醇丙酮酸羧激酶 (PEPCK 或 PCK1)。
在脂肪组织中,NR1H3 的激活导致胰岛素敏感葡萄糖转运体 GLUT4 的转录诱导。
相比之下,LXRβ (NR1H2) 的基础表达已被证明对由另一核受体糖皮质激素受体 (GR, NR3C1) 调节的 PCK1 至关重要。
LXR 在肝脏中似乎具有相反的作用,因为 NR1H3 (LXRα) 的激活通过抑制由糖皮质激素诱导的 PCK1 mRNA 表达,而 NR1H2 (LXRβ) 的拮抗减少糖皮质激素诱导的 PCK1 mRNA 表达。
由于 NR1H3 (LXRα) 的激活通过抑制糖皮质激素诱导的 PCK1 mRNA 表达,而 NR1H2 (LXRβ) 的拮抗减少糖皮质激素诱导的 PCK1 mRNA 表达,LXR 在肝脏中似乎具有相反的作用,因为 NR1H3 (LXRα) 的激活通过抑制由糖皮质激素诱导的 PCK1 mRNA 表达,而 NR1H2 (LXRβ) 的拮抗减少糖皮质激素诱导的 PCK1 mRNA 表达。
英文描述
NR1H2 & NR1H3 regulate gene expression linked to gluconeogenesis Activation of liver X receptor α (LXRα, NR1H3) alters the expression of genes in liver and adipose tissue that collectively may limit hepatic glucose output and improve peripheral glucose uptake (Laffitte BA et al. 2003). In the liver, activation of NR1H3 led to the suppression of the expression of genes involved in gluconeogenesis including glucose-6-phosphatase (G6Pase) and phosphoenolpyruvate carboxykinase (PCK1 or PEPCK) (Laffitte BA et al. 2003; Dalen KT et al. 2003; Herzog B et al. 2007; Commerford et al. 2007). In adipose tissue, activation of NR1H3 led to the transcriptional induction of the insulin-sensitive glucose transporter, GLUT4 (Laffitte BA et al. 2003; Dalen KT et al. 2003). In contrast, basal expression of LXRβ (NR1H2) has been shown to be essential for the regulation of PCK1 by another nuclear receptor, the glucocorticoid receptor GR (NR3C1) (Patel et al. 2011; Patel et. al. 2017). The LXRs appear to have somewhat opposing roles in the regulation of PCK1 in the liver since NR1H3 (LXRα) activation represses PCK1 mRNA expression induced by glucocorticoids (Nader et al. 2012) and NR1H2 (LXRβ) antagonism reduces glucocorticoid-induced PCK1 mRNA expression (Patel et al. 2017).

所含基因

5 个基因