ArticleThe Journal of biological chemistry2016
Activation of Transmembrane Bile Acid Receptor TGR5 Modulates Pancreatic Islet α Cells to Promote Glucose Homeostasis.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05906641 (Modulation of Secondary Bile Acids Through the Intestinal Microbiota After Consumption of a High-protein Diet.), which is not on this map. Cited by 72 papers, 2 of them syntheses that pooled it.
What it found
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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.
Modulation of Secondary Bile Acids Through the Intestinal Microbiota After Consumption of a High-protein Diet.
Who cites it
72 citing papers in PubMed, 2 syntheses or guidelines pooled it, 129 citations in OpenAlex.
- Reduced Systemic Levels of Bile Acids in Individuals with Coronary Artery Disease: Insights from a Systematic Review.International journal of molecular sciences · 2025Pooled it
- Pooled it
- Review
- Bile acid signaling in health and disease.Molecular biomedicine · 2026Review
- Foods as Modulators of GLP-1 Secretion.Nutrients · 2026Review
- Physiological Functions of Side-Chain-Retaining Sterols in the Brain and Their Roles in Neurodegenerative Diseases.Metabolites · 2026Review
- Bile acid signaling: from dynamic pool composition to inter-organ communication.Frontiers in endocrinology · 2026Review
- Bile acids and bile acid modification in health and disease: from novel modifications to therapeutic interventions.Frontiers in endocrinology · 2026Review
- Legume intake on gut microbiome and glycemia in type 2 diabetes management: narrative review.Frontiers in nutrition · 2026Review
- Beyond conventional therapies: Gut microbiota modulation and macromolecular drugs in the battle against cardiometabolic diseases.Journal of pharmaceutical analysis · 2026Review
- Increased dietary protein stimulates amino acid catabolism via the gut microbiota and secondary bile acid production.Gut microbes · 2025Article
- Biological functions and pharmacological behaviors of bile acids in metabolic diseases.Journal of advanced research · 2025Review
- Multifaceted Interactions Between Bile Acids, Their Receptors, and MASH: From Molecular Mechanisms to Clinical Therapeutics.Molecules (Basel, Switzerland) · 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
- Biological Actions of Bile Acids via Cell Surface Receptors.International journal of molecular sciences · 2025Review
- The Mechanistic Target of Rapamycin MediatesMicroorganisms · 2025Article
- The discovery of a new nonbile acid modulator of Takeda G protein-coupled receptor 5: An integrated computational approach.Archiv der Pharmazie · 2025Article
- Bile acids and gestational diabetes mellitus: exploring the link and implications - a review.Frontiers in endocrinology · 2025Review
- Recent advancements in the structural exploration of TGR5 agonists for diabetes treatment.RSC medicinal chemistry · 2024Review
- Vagal activation alters prandial bile acid composition and glycemia in patients with hypoglycemia after Roux-en-Y gastric bypass surgery.Neurogastroenterology and motility · 2024Article
12 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
10 authors at 2 institutions in 1 country.
Funding
Abstract
The physiological role of the TGR5 receptor in the pancreas is not fully understood. We previously showed that activation of TGR5 in pancreatic β cells by bile acids induces insulin secretion. Glucagon released from pancreatic α cells and glucagon-like peptide 1 (GLP-1) released from intestinal L cells regulate insulin secretion. Both glucagon and GLP-1 are derived from alternate splicing of a common precursor, proglucagon by PC2 and PC1, respectively. We investigated whether TGR5 activation in pancreatic α cells enhances hyperglycemia-induced PC1 expression thereby releasing GLP-1, which in turn increases β cell mass and function in a paracrine manner. TGR5 activation augmented a hyperglycemia-induced switch from glucagon to GLP-1 synthesis in human and mouse islet α cells by GS/cAMP/PKA/cAMP-response element-binding protein-dependent activation of PC1. Furthermore, TGR5-induced GLP-1 release from α cells was via an Epac-mediated PKA-independent mechanism. Administration of the TGR5 agonist, INT-777, to db/db mice attenuated the increase in body weight and improved glucose tolerance and insulin sensitivity. INT-777 augmented PC1 expression in α cells and stimulated GLP-1 release from islets of db/db mice compared with control. INT-777 also increased pancreatic β cell proliferation and insulin synthesis. The effect of TGR5-mediated GLP-1 from α cells on insulin release from islets could be blocked by GLP-1 receptor antagonist. These results suggest that TGR5 activation mediates cross-talk between α and β cells by switching from glucagon to GLP-1 to restore β cell mass and function under hyperglycemic conditions. Thus, INT-777-mediated TGR5 activation could be leveraged as a novel way to treat type 2 diabetes mellitus.
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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.