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Farnesoid X receptor is inhibited after ileum transposition in diabetic rats: its hypoglycemic effect
Background: Aim to investigate bile acid profile changes and the Farnesoid X receptor (FXR) status after ileotransposition (IT), and reveal its possible hypoglycemic mechanism. Methods: Twenty male diabetic rats were randomly assigned into the IT group and the sham IT (SH) group. Bile acid profiles...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Ivyspring International Publisher
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10110471/ https://www.ncbi.nlm.nih.gov/pubmed/37082732 http://dx.doi.org/10.7150/ijms.80563 |
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author | Chen, Weijie Zhou, Shengnan Xiao, Jianchun Liu, Wei Qu, Qiang He, Xiaodong |
author_facet | Chen, Weijie Zhou, Shengnan Xiao, Jianchun Liu, Wei Qu, Qiang He, Xiaodong |
author_sort | Chen, Weijie |
collection | PubMed |
description | Background: Aim to investigate bile acid profile changes and the Farnesoid X receptor (FXR) status after ileotransposition (IT), and reveal its possible hypoglycemic mechanism. Methods: Twenty male diabetic rats were randomly assigned into the IT group and the sham IT (SH) group. Bile acid profiles were measured using an ultra-performance liquid chromatography-tandem mass spectrometry. Glucose metabolism was monitored after oral administration of FXR inhibitor and agonist. And the expression of key FXR target genes were measured. Results: The levels of β-muricholic acid (P = 0.047), tauro-α-muricholic acid and tauro-β-muricholic acid (P < 0.001) in plasma in the IT group were higher than those in the SH group, and the levels of taurocholic acid (P = 0.049) and turoursodeoxycholic acid (P = 0.030) were lower than those in the SH group. After inhibition of intestinal FXR, the glucose metabolism in the SH group was improved. When FXR agonist was given, the blood glucose level was increased in both groups. After sacrifice, the levels of glycoursodeoxycholic acid, tauro-α-muricholic acid and tauro-β-muricholic acid in liver and ileum tissues were higher than those in the SH group (P < 0.05), the level of α- muricholic acid (P < 0.001) in liver tissues were lower than that in the SH group. Moreover, the expression of CYP7A1 mRNA (P < 0.001) and FGF15 mRNA (P = 0.001) in the IT group was significantly higher, and the expression of PEPCK mRNA (P = 0.004), SREPB1c mRNA (P = 0.005) and SRB1 mRNA (P = 0.001) were significantly lower than that in the SH group. Conclusions: We demonstrate a remarkable heterogeneity of BA profiles after IT, FXR activation might has a detrimental effect on glucose metabolism. |
format | Online Article Text |
id | pubmed-10110471 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Ivyspring International Publisher |
record_format | MEDLINE/PubMed |
spelling | pubmed-101104712023-04-19 Farnesoid X receptor is inhibited after ileum transposition in diabetic rats: its hypoglycemic effect Chen, Weijie Zhou, Shengnan Xiao, Jianchun Liu, Wei Qu, Qiang He, Xiaodong Int J Med Sci Research Paper Background: Aim to investigate bile acid profile changes and the Farnesoid X receptor (FXR) status after ileotransposition (IT), and reveal its possible hypoglycemic mechanism. Methods: Twenty male diabetic rats were randomly assigned into the IT group and the sham IT (SH) group. Bile acid profiles were measured using an ultra-performance liquid chromatography-tandem mass spectrometry. Glucose metabolism was monitored after oral administration of FXR inhibitor and agonist. And the expression of key FXR target genes were measured. Results: The levels of β-muricholic acid (P = 0.047), tauro-α-muricholic acid and tauro-β-muricholic acid (P < 0.001) in plasma in the IT group were higher than those in the SH group, and the levels of taurocholic acid (P = 0.049) and turoursodeoxycholic acid (P = 0.030) were lower than those in the SH group. After inhibition of intestinal FXR, the glucose metabolism in the SH group was improved. When FXR agonist was given, the blood glucose level was increased in both groups. After sacrifice, the levels of glycoursodeoxycholic acid, tauro-α-muricholic acid and tauro-β-muricholic acid in liver and ileum tissues were higher than those in the SH group (P < 0.05), the level of α- muricholic acid (P < 0.001) in liver tissues were lower than that in the SH group. Moreover, the expression of CYP7A1 mRNA (P < 0.001) and FGF15 mRNA (P = 0.001) in the IT group was significantly higher, and the expression of PEPCK mRNA (P = 0.004), SREPB1c mRNA (P = 0.005) and SRB1 mRNA (P = 0.001) were significantly lower than that in the SH group. Conclusions: We demonstrate a remarkable heterogeneity of BA profiles after IT, FXR activation might has a detrimental effect on glucose metabolism. Ivyspring International Publisher 2023-04-02 /pmc/articles/PMC10110471/ /pubmed/37082732 http://dx.doi.org/10.7150/ijms.80563 Text en © The author(s) https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions. |
spellingShingle | Research Paper Chen, Weijie Zhou, Shengnan Xiao, Jianchun Liu, Wei Qu, Qiang He, Xiaodong Farnesoid X receptor is inhibited after ileum transposition in diabetic rats: its hypoglycemic effect |
title | Farnesoid X receptor is inhibited after ileum transposition in diabetic rats: its hypoglycemic effect |
title_full | Farnesoid X receptor is inhibited after ileum transposition in diabetic rats: its hypoglycemic effect |
title_fullStr | Farnesoid X receptor is inhibited after ileum transposition in diabetic rats: its hypoglycemic effect |
title_full_unstemmed | Farnesoid X receptor is inhibited after ileum transposition in diabetic rats: its hypoglycemic effect |
title_short | Farnesoid X receptor is inhibited after ileum transposition in diabetic rats: its hypoglycemic effect |
title_sort | farnesoid x receptor is inhibited after ileum transposition in diabetic rats: its hypoglycemic effect |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10110471/ https://www.ncbi.nlm.nih.gov/pubmed/37082732 http://dx.doi.org/10.7150/ijms.80563 |
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