ReferenceID 2084
Hyocholic acid species improve glucose homeostasis through a distinct TGR5 and FXR signaling mechanism
Cell Metab
Hyocholic acid (HCA) and its derivatives are found in trace amounts in human blood but constitute approximately 76% of the bile acid (BA) pool in pigs, a species known for its exceptional resistance to type 2 diabetes. H
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Record Fields
Scalar fields from the final reference record.
- Reference Id
- 2084
- Evidence Id
- 18674
- Core Evidence Id
- 18674
- Source Reference Id
- 4182
- Herb2 Reference Id
- HBREF004979
- Subject Paper Key
- HBIN029808_33338411
- Pubmed Id
- 33338411
- Doi
- 10.1016/j.cmet.2020.11.017
- Paper Title
- Hyocholic acid species improve glucose homeostasis through a distinct TGR5 and FXR signaling mechanism
- Paper Abstract
- Hyocholic acid (HCA) and its derivatives are found in trace amounts in human blood but constitute approximately 76% of the bile acid (BA) pool in pigs, a species known for its exceptional resistance to type 2 diabetes. Here, we show that BA depletion in pigs suppressed secretion of glucagon-like peptide-1 (GLP-1) and increased blood glucose levels. HCA administration in diabetic mouse models improved serum fasting GLP-1 secretion and glucose homeostasis to a greater extent than tauroursodeoxycholic acid. HCA upregulated GLP-1 production and secretion in enteroendocrine cells via simultaneously activating G-protein-coupled BA receptor, TGR5, and inhibiting farnesoid X receptor (FXR), a unique mechanism that is not found in other BA species. We verified the findings in TGR5 knockout, intestinal FXR activation, and GLP-1 receptor inhibition mouse models. Finally, we confirmed in a clinical cohort, that lower serum concentrations of HCA species were associated with diabetes and closely related to glycemic markers.
- Journal
- Cell Metab
- Publish Year
- 2021
- Experiment Subject
- mouse; human; pig
- Experiment Type
- Clinical & Animal Experiment
- Phenotype Related
- Diabetes; Type 2 Diabetes; Diabetic
- Paper Title Cn
- Paper Title En
- Hyocholic acid species improve glucose homeostasis through a distinct TGR5 and FXR signaling mechanism
- Bilingual Status
- semi_complete