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Publication : Loss of Cyp8b1 improves glucose homeostasis by increasing GLP-1.

First Author  Kaur A Year  2015
Journal  Diabetes Volume  64
Issue  4 Pages  1168-79
PubMed ID  25338812 Mgi Jnum  J:243988
Mgi Id  MGI:5912767 Doi  10.2337/db14-0716
Citation  Kaur A, et al. (2015) Loss of Cyp8b1 improves glucose homeostasis by increasing GLP-1. Diabetes 64(4):1168-79
abstractText  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 12alpha-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 beta-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 beta-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.
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