Basic Study
Copyright ©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Diabetes. Jun 15, 2025; 16(6): 103616
Published online Jun 15, 2025. doi: 10.4239/wjd.v16.i6.103616
Pig bile powder maintains blood glucose homeostasis by promoting glucagon-like peptide-1 secretion via inhibiting farnesoid X receptor
Yi-Min Sun, Jun-Liang Kuang, Hui-Heng Zhang, Xi-Xi Xia, Jie-Yi Wang, Dan Zheng, Ke-Jun Zhou, Ya-Jun Tang, Ai-Hua Zhao, Wei Jia, Guo-Xiang Xie, Xiao-Jiao Zheng
Yi-Min Sun, Jun-Liang Kuang, Hui-Heng Zhang, Xi-Xi Xia, Jie-Yi Wang, Dan Zheng, Ya-Jun Tang, Ai-Hua Zhao, Xiao-Jiao Zheng, Center for Translational Medicine, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200233, China
Ke-Jun Zhou, Guo-Xiang Xie, Human Metabolomics Institute, Inc., Shenzhen 518109, Guangdong Province, China
Wei Jia, Department of Pharmacology and Pharmacy, University of Hong Kong, Hongkong 999077, China
Co-first authors: Yi-Min Sun and Jun-Liang Kuang.
Co-corresponding authors: Guo-Xiang Xie and Xiao-Jiao Zheng.
Author contributions: Zheng XJ, Xie GX, and Jia W conceptualized and designed the study; Zheng XJ, Xie GX, Tang YJ, and Zhao AH coordinated the experimental planning and execution; Kuang JL, Sun YM, Zhang HH, Xia XX, Wang JY, and Zhou KJ were responsible for the mouse experiments; Sun YM, Kuang JL, and Wang JY were responsible for cell studies; Zhao AH, Kuang JL, and Zheng D were responsible for sample preparation and chemical composition analysis of bile powder; Sun YM, Kuang JL, and Zhang HH performed the data preprocessing and statistical analysis; Sun YM and Kuang JL drafted the manuscript and produced the figures, meriting their designation of co-first authorship; Zheng XJ and Xie GX critically revised the manuscript, meriting their designation of co-corresponding authorship.
Supported by the National Natural Science Foundation of China, No. 82122012, No. 82270917, No. 82170833 and No. 82170601; Shanghai Sixth People’s Hospital Project, No. ynjq202401 and No. ynms202117; and Shanghai Research Center for Endocrine and Metabolic Diseases, No. 2022ZZ01002.
Institutional review board statement: This study does not involve any human experiments.
Institutional animal care and use committee statement: Institutional animal care and use committee statement: The animal feeding and animal experiments of this project strictly follow the experimental animal welfare policy. All experimental operations and experimental inspections are carried out after the use of isoflurane. The researchers do their best to reduce and eliminate the fear and pain of experimental animals. The Institutional Animal Care and Use Committee of Shanghai Jiao Tong University School of Medicine affiliated Shanghai Sixth People’s Hospital approved the animal experimental research project (No. DWLL2024-1028).
Conflict-of-interest statement: The authors declare that they have no conflict of interest.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Data sharing statement: No additional data are available.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Xiao-Jiao Zheng, PhD, Center for Translational Medicine, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, No. 600 Yishan Road, Shanghai 200233, China. joyzheng99@sjtu.edu.cn
Received: December 16, 2024
Revised: March 13, 2025
Accepted: April 25, 2025
Published online: June 15, 2025
Processing time: 181 Days and 6.3 Hours
Abstract
BACKGROUND

Traditional Chinese medicine offers many valuable remedies for maintaining blood glucose homeostasis in patients with type 2 diabetes mellitus. Bile powder (BP) is a powdered form of bile derived from pigs. It has been used historically in various medicinal applications. Currently, the therapeutic potential of BP in regulating glucose homeostasis remains unclear. Bile acids (BAs) are increasingly recognized for their role in glucose metabolism particularly through the modulation of glucagon-like peptide-1 (GLP-1).

AIM

To investigate BP effects on glucose homeostasis and elucidate its mechanistic role through GLP-1 and farnesoid X receptor (FXR) signaling.

METHODS

A diabetic mouse model was established using a high-fat diet and streptozotocin administration. Mice were treated with BP at doses of 25, 50, or 75 mg/kg/day for 45 days. Glucose homeostasis was assessed via the oral glucose tolerance test and insulin tolerance test. Serum GLP-1 levels were measured by enzyme-linked immunosorbent assay. A GLP-1 receptor antagonist and an FXR agonist were used to clarify the underlying mechanisms. In vitro STC-1 murine enteroendocrine cells were treated with a BP-mimicking BA mixture to assess GLP-1 secretion and proglucagon gene expression.

RESULTS

BP treatment significantly improved glucose homeostasis in the diabetic mouse model as indicated by lower blood glucose (P < 0.05) and improved insulin sensitivity. BP enhanced GLP-1 secretion (P < 0.05), which was an effect abolished by the GLP-1 receptor antagonist. This observation confirmed its dependence on GLP-1 signaling. In STC-1 cells, BP-derived BA mixtures stimulated GLP-1 secretion and upregulated proglucagon expression (P < 0.05). Mechanistically, BP inhibited FXR signaling as evidenced by the reversal of its effects upon fexaramine administration. In addition, long-term BP treatment suppressed FXR signaling, resulting in elevated GLP-1 levels and preventing glucose dysregulation.

CONCLUSION

BP improved glucose homeostasis by promoting GLP-1 secretion via FXR inhibition, highlighting its potential as a therapeutic strategy for metabolic disorders.

Keywords: Pig bile powder; Type 2 diabetes mellitus; Glucagon-like peptide 1; Farnesoid X receptor; Traditional Chinese medicine

Core Tip: Traditional Chinese medicine has several substances that regulate blood glucose in the treatment of type 2 diabetes mellitus. One of these substances is pig bile powder (BP). However, its mechanism of action remains unclear. This study demonstrated that BP treatment improved glucose tolerance and insulin sensitivity in a diabetic mouse model. Bile acids in the BP act as farnesoid X receptor antagonists and enhance glucagon-like peptide-1 production. Glucagon-like peptide-1 is a key hormone for glucose regulation. Our findings furthered the understanding of the therapeutic potential of BP for type 2 diabetes mellitus treatment.