Loss of Cyp8b1 Improves Glucose Homeostasis by Increasing GLP-1
Loss of Cyp8b1 Improves Glucose Homeostasis by Increasing GLP-1
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DOI：
10.2337/db15-0518
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发表时间：
2015-04-01
期刊：
影响因子：
7.7
通讯作者：
Hayden, Michael R.
中科院分区：
文献类型：
--
作者：
Kaur, Achint;Patankar, Jay V.;Hayden, Michael R.
除了促进脂质吸收的作用外，胆汁酸越来越被认为是激活细胞信号受体的信号分子。靶向破坏甾醇12-羟化酶基因（Cyp8b1）导致胆酸（CA）及其衍生物完全缺失。在这里，我们研究Cyp8b1缺失对葡萄糖稳态的影响。Cyp8b1缺失导致葡萄糖耐量、胰岛素敏感性和-细胞功能的改善，这是由Cyp8b1（-/-）小鼠CA缺失介导的。此外，我们表明，在缺乏胆道CA的情况下，肠道脂肪吸收减少导致到达回肠L细胞的游离脂肪酸增加。这与促肠促素GLP-1分泌增加有关。反过来，GLP-1增加了-细胞的胰岛素的生物合成和分泌，导致在Cyp8b1（-/-）小鼠中观察到的葡萄糖耐量改善。因此，我们的数据阐明了Cyp8b1抑制对葡萄糖代谢调节的重要性。
Besides their role in facilitating lipid absorption, bile acids are increasingly being recognized as signaling molecules that activate cell-signaling receptors. Targeted disruption of the sterol 12-hydroxylase gene (Cyp8b1) results in complete absence of cholic acid (CA) and its derivatives. Here we investigate the effect of Cyp8b1 deletion on glucose homeostasis. Absence of Cyp8b1 results in improved glucose tolerance, insulin sensitivity, and -cell function, mediated by absence of CA in Cyp8b1(-/-) mice. In addition, we show that reduced intestinal fat absorption in the absence of biliary CA leads to increased free fatty acids reaching the ileal L cells. This correlates with increased secretion of the incretin hormone GLP-1. GLP-1, in turn, increases the biosynthesis and secretion of insulin from -cells, leading to the improved glucose tolerance observed in the Cyp8b1(-/-) mice. Thus, our data elucidate the importance of Cyp8b1 inhibition on the regulation of glucose metabolism.