ArticleFrontiers in physiology2014
Release of GLP-1 and PYY in response to the activation of G protein-coupled bile acid receptor TGR5 is mediated by Epac/PLC-ε pathway and modulated by endogenous H2S.
Article in Frontiers in physiology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
65 citing papers in PubMed, 1 synthesis or guideline pooled it, 112 citations in OpenAlex.
- The Role of Short-Chain Fatty Acids in Microbiota-Gut-Brain Cross-Talk with a Focus on Amyotrophic Lateral Sclerosis: A Systematic Review.International journal of molecular sciences · 2023Pooled it
- Chenodeoxycholic acid stimulates glucagon-like peptide-1 secretion in patients after Roux-en-Y gastric bypass.Physiological reports · 2017Trial
- Intestinal gases as markers to study the diet-gut microbiota-host metabolism axis in humans and their relationship to metabolic health.Gut microbes · 2026Review
- Glucagon-like peptide-1: a critical link between gut microbiota dysbiosis and degenerative musculoskeletal diseases.Gut microbes · 2026Review
- Activation of the TGR5/cAMP/PKA/CREB axis in cholangiocytes mediates epithelial-mesenchymal transition and fibrosis in hepatolithiasis.Biology direct · 2026Article
- Fermented Plant-Based Foods and Postbiotics for Glycemic Control-Microbial Biotransformation of Phytochemicals.Molecules (Basel, Switzerland) · 2026Review
- Crosstalk Between HHandbook of experimental pharmacology · 2026Review
- The role of bile acid-activated receptor TGR5 in inflammation and liver diseases.Frontiers in physiology · 2026Review
- Peptide YY in Type 2 Diabetes: A Complementary Gut Hormone with Therapeutic Potential Beyond GLP-1.Nutrients · 2025Review
- The Critical Role of the Bile Acid Receptor TGR5 in Energy Homeostasis: Insights into Physiology and Therapeutic Potential.International journal of molecular sciences · 2025Review
- Rewiring the Brain Through the Gut: Insights into Microbiota-Nervous System Interactions.Current issues in molecular biology · 2025Review
- Bile Acids and Type 2 Diabetes: Roles in Glucose Homeostasis and Therapeutic Opportunities.Metabolites · 2025Review
- Integration of signal transduction pathways in sensory epithelial enteroendocrine cells.Molecular biology of the cell · 2025Review
- Microbiota-neuroepithelial signalling across the gut-brain axis.Nature reviews. Microbiology · 2025Review
- Western Diet and fecal microbiota transplantation alter phenotypic, liver fatty acids, and gut metagenomics and metabolomics in Mtarc2 knockout mice.Genes & nutrition · 2025Article
- Unraveling the gut microbiota's role in obesity: key metabolites, microbial species, and therapeutic insights.Journal of bacteriology · 2025Review
- The Enteric Neuronal Circuitry: A Key Ignored Player in Nutrient Sensing Along the Gut-Brain Axis.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Review
- Select microbial metabolites in the small intestinal lumen regulate vagal activity via receptor-mediated signaling.iScience · 2025Article
- Antibiotic-induced gut microbiota depletion enhances glucose tolerance linked to GLP-1 signaling.Frontiers in endocrinology · 2025Article
- Untargeted metabolomic analysis uncovers metabolic variability of fourFrontiers in microbiology · 2025Article
5 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Activation of plasma membrane TGR5 receptors in enteroendocrine cells by bile acids is known to regulate gastrointestinal secretion and motility and glucose homeostasis. The endocrine functions of the gut are modulated by microenvironment of the distal gut predominantly by sulfur-reducing bacteria of the microbiota that produce H2S. However, the mechanisms involved in the release of peptide hormones, GLP-1 and PYY in response to TGR5 activation by bile acids and the effect of H2S on bile acid-induced release of GLP-1 and PYY are unclear. In the present study, we have identified the signaling pathways activated by the bile acid receptor TGR5 to mediate GLP-1 and PYY release and the mechanism of inhibition of their release by H2S in enteroendocrine cells. The TGR5 ligand oleanolic acid (OA) stimulated Gαs and cAMP formation, and caused GLP-1 and PYY release. OA-induced cAMP formation and peptide release were blocked by TGR5 siRNA. OA also caused an increase in PI hydrolysis and intracellular Ca(2+). Increase in PI hydrolysis was abolished in cells transfected with PLC-ε siRNA. 8-pCPT-2'-O-Me-cAMP, a selective activator of Epac, stimulated PI hydrolysis, and GLP-1 and PYY release. L-Cysteine, which activates endogenous H2S producing enzymes cystathionine-γ-lyase and cystathionine-β-synthase, and NaHS and GYY4137, which generate H2S, inhibited PI hydrolysis and GLP-1 and PYY release in response to OA or 8-pCPT-2'-O-Me-cAMP. Propargylglycine, an inhibitor of CSE, reversed the effect of L-cysteine on PI hydrolysis and GLP-1 and PYY release. We conclude: (i) activation of Gαs-coupled TGR5 receptors causes stimulation of PI hydrolysis, and release of GLP-1 and PYY via a PKA-independent, cAMP-dependent mechanism involving Epac/PLC-ε/Ca(2+) pathway, and (ii) H2S has potent inhibitory effects on GLP-1 and PYY release in response to TGR5 activation, and the mechanism involves inhibition of PLC-ε/Ca(2+) pathway.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.