ArticleThe Journal of clinical investigation2022
Haploinsufficiency of CYP8B1 associates with increased insulin sensitivity in humans.
Article in The Journal of clinical investigation, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 33 citations in OpenAlex.
- Structure-Based Drug Design of Quinoline CYP8B1 Inhibitors for the Potential Treatment of Metabolic Disease.ACS medicinal chemistry letters · 2026Article
- Bile acid signaling in health and disease.Molecular biomedicine · 2026Review
- mTORC1-TFEB/TFE3 signaling is associated with bile acid diversification during hepatic metabolic adaptation.Science advances · 2026Article
- Alcohol-related liver disease disrupts bile acid homeostasis and gut microbial bile acid metabolism.JHEP reports : innovation in hepatology · 2026Article
- Gut Microbiota-Bile Acid Axis in Type 2 Diabetes-Associated Gallbladder Diseases: Mechanisms and Therapeutic Potential.Metabolites · 2026Review
- Bile acids regulate lipid metabolism through selective actions on fatty acid absorption.Cell metabolism · 2026Article
- Bile acid-axis dysregulation in MASLD/MASH progression: from metabolic mismatch to inflammatory-fibrotic remodeling.Frontiers in medicine · 2026Review
- Review
- Differential roles of individual bile acid in physiology and disease.Pharmacological research · 2025Review
- Bile Acids and Type 2 Diabetes: Roles in Glucose Homeostasis and Therapeutic Opportunities.Metabolites · 2025Review
- Unresolved alterations in bile acid composition and dyslipidemia in maternal and cord blood after UDCA treatment for intrahepatic cholestasis of pregnancy.American journal of physiology. Gastrointestinal and liver physiology · 2025Article
- Bile acid metabolism in type 2 diabetes mellitus.Nature reviews. Endocrinology · 2025Review
- Effects ofFrontiers in pharmacology · 2025Article
- Implementation of the Methyl-Seq platform to identify tissue- and sex-specific DNA methylation differences in the rat epigenome.Epigenetics · 2024Article
- Bile Acid Signaling in Metabolic and Inflammatory Diseases and Drug Development.Pharmacological reviews · 2024Review
- A new mechanism of thyroid hormone receptor β agonists ameliorating nonalcoholic steatohepatitis by inhibiting intestinal lipid absorption via remodeling bile acid profiles.Acta pharmacologica Sinica · 2024Article
- Article
- High-Fat Diet-Induced Decreased Circulating Bile Acids Contribute to Obesity Associated with Gut Microbiota in Mice.Foods (Basel, Switzerland) · 2024Article
- Gut microbiota and metabolomic profile changes play critical roles in tacrolimus-induced diabetes in rats.Frontiers in cellular and infection microbiology · 2024Article
- Decreased FXR Agonism in the Bile Acid Pool Is Associated with Impaired FXR Signaling in a Pig Model of Pediatric NAFLD.Biomedicines · 2023Article
Corrections and comments
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Authors and funding
26 authors at 10 institutions in 5 countries.
Funding
Abstract
BACKGROUNDCytochrome P450 family 8 subfamily B member 1 (CYP8B1) generates 12α-hydroxylated bile acids (BAs) that are associated with insulin resistance in humans.METHODSTo determine whether reduced CYP8B1 activity improves insulin sensitivity, we sequenced CYP8B1 in individuals without diabetes and identified carriers of complete loss-of-function (CLOF) mutations utilizing functional assays.RESULTSMutation carriers had lower plasma 12α-hydroxylated/non-12α-hydroxylated BA and cholic acid (CA)/chenodeoxycholic acid (CDCA) ratios compared with age-, sex-, and BMI-matched controls. During insulin clamps, hepatic glucose production was suppressed to a similar magnitude by insulin, but glucose infusion rates to maintain euglycemia were higher in mutation carriers, indicating increased peripheral insulin sensitivity. Consistently, a polymorphic CLOF CYP8B1 mutation associated with lower fasting insulin in the AMP-T2D-GENES study. Exposure of primary human muscle cells to mutation-carrier CA/CDCA ratios demonstrated increased FOXO1 activity, and upregulation of both insulin signaling and glucose uptake, which were mediated by increased CDCA. Inhibition of FOXO1 attenuated the CDCA-mediated increase in muscle insulin signaling and glucose uptake. We found that reduced CYP8B1 activity associates with increased insulin sensitivity in humans.CONCLUSIONOur findings suggest that increased circulatory CDCA due to reduced CYP8B1 activity increases skeletal muscle insulin sensitivity, contributing to increased whole-body insulin sensitization.FUNDINGBiomedical Research Council/National Medical Research Council of Singapore.
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