{"title":"猪胆汁粉通过抑制法内酯X受体促进胰高血糖素样肽-1的分泌，维持血糖稳态。","authors":"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","doi":"10.4239/wjd.v16.i6.103616","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>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).</p><p><strong>Aim: </strong>To investigate BP effects on glucose homeostasis and elucidate its mechanistic role through GLP-1 and farnesoid X receptor (FXR) signaling.</p><p><strong>Methods: </strong>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 <i>via</i> 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. <i>In vitro</i> STC-1 murine enteroendocrine cells were treated with a BP-mimicking BA mixture to assess GLP-1 secretion and proglucagon gene expression.</p><p><strong>Results: </strong>BP treatment significantly improved glucose homeostasis in the diabetic mouse model as indicated by lower blood glucose (<i>P</i> < 0.05) and improved insulin sensitivity. BP enhanced GLP-1 secretion (<i>P</i> < 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 (<i>P</i> < 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.</p><p><strong>Conclusion: </strong>BP improved glucose homeostasis by promoting GLP-1 secretion <i>via</i> FXR inhibition, highlighting its potential as a therapeutic strategy for metabolic disorders.</p>","PeriodicalId":48607,"journal":{"name":"World Journal of Diabetes","volume":"16 6","pages":"103616"},"PeriodicalIF":4.6000,"publicationDate":"2025-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12179914/pdf/","citationCount":"0","resultStr":"{\"title\":\"Pig bile powder maintains blood glucose homeostasis by promoting glucagon-like peptide-1 secretion <i>via</i> inhibiting farnesoid X receptor.\",\"authors\":\"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\",\"doi\":\"10.4239/wjd.v16.i6.103616\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>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).</p><p><strong>Aim: </strong>To investigate BP effects on glucose homeostasis and elucidate its mechanistic role through GLP-1 and farnesoid X receptor (FXR) signaling.</p><p><strong>Methods: </strong>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 <i>via</i> 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. <i>In vitro</i> STC-1 murine enteroendocrine cells were treated with a BP-mimicking BA mixture to assess GLP-1 secretion and proglucagon gene expression.</p><p><strong>Results: </strong>BP treatment significantly improved glucose homeostasis in the diabetic mouse model as indicated by lower blood glucose (<i>P</i> < 0.05) and improved insulin sensitivity. BP enhanced GLP-1 secretion (<i>P</i> < 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 (<i>P</i> < 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.</p><p><strong>Conclusion: </strong>BP improved glucose homeostasis by promoting GLP-1 secretion <i>via</i> FXR inhibition, highlighting its potential as a therapeutic strategy for metabolic disorders.</p>\",\"PeriodicalId\":48607,\"journal\":{\"name\":\"World Journal of Diabetes\",\"volume\":\"16 6\",\"pages\":\"103616\"},\"PeriodicalIF\":4.6000,\"publicationDate\":\"2025-06-15\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12179914/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"World Journal of Diabetes\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.4239/wjd.v16.i6.103616\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"ENDOCRINOLOGY & METABOLISM\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"World Journal of Diabetes","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.4239/wjd.v16.i6.103616","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ENDOCRINOLOGY & METABOLISM","Score":null,"Total":0}
Pig bile powder maintains blood glucose homeostasis by promoting glucagon-like peptide-1 secretion via inhibiting farnesoid X receptor.
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.
期刊介绍：
The WJD is a high-quality, peer reviewed, open-access journal. The primary task of WJD is to rapidly publish high-quality original articles, reviews, editorials, and case reports in the field of diabetes. In order to promote productive academic communication, the peer review process for the WJD is transparent; to this end, all published manuscripts are accompanied by the anonymized reviewers’ comments as well as the authors’ responses. The primary aims of the WJD are to improve diagnostic, therapeutic and preventive modalities and the skills of clinicians and to guide clinical practice in diabetes. Scope: Diabetes Complications, Experimental Diabetes Mellitus, Type 1 Diabetes Mellitus, Type 2 Diabetes Mellitus, Diabetes, Gestational, Diabetic Angiopathies, Diabetic Cardiomyopathies, Diabetic Coma, Diabetic Ketoacidosis, Diabetic Nephropathies, Diabetic Neuropathies, Donohue Syndrome, Fetal Macrosomia, and Prediabetic State.
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