ArticleActa pharmacologica Sinica2016
OL3, a novel low-absorbed TGR5 agonist with reduced side effects, lowered blood glucose via dual actions on TGR5 activation and DPP-4 inhibition.
Article in Acta pharmacologica Sinica, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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
10 citing papers in PubMed, 25 citations in OpenAlex.
- Phillygenin ameliorates tight junction proteins reduction, fibrosis, and apoptosis in mice with chronic colitis via TGR5-mediated PERK-eIF2α-CaJournal of pharmaceutical analysis · 2025Article
- TGR5 agonist inhibits intestinal epithelial cell apoptosis via cAMP/PKA/c-FLIP/JNK signaling pathway and ameliorates dextran sulfate sodium-induced ulcerative colitis.Acta pharmacologica Sinica · 2023Article
- Design, Synthesis, Computational and Biological Evaluation of Novel Structure Fragments Based on Lithocholic Acid (LCA).Molecules (Basel, Switzerland) · 2023Article
- Trust Your Gut: Strategies and Tactics for Intestinally Restricted Drugs.ACS medicinal chemistry letters · 2023Review
- Article
- Improving glucose and lipids metabolism: drug development based on bile acid related targets.Cell stress · 2021Review
- (E)-7-Ethylidene-lithocholic Acid (7-ELCA) Is a Potent Dual Farnesoid X Receptor (FXR) Antagonist and GPBAR1 Agonist Inhibiting FXR-Induced Gene Expression in Hepatocytes and Stimulating Glucagon-like Peptide-1 Secretion From Enteroendocrine Cells.Frontiers in pharmacology · 2021Article
- Amelioration of Endothelial Dysfunction in Diabetes: Role of Takeda G Protein-Coupled Receptor 5.Frontiers in pharmacology · 2021Review
- Intestinal TGR5 agonism improves hepatic steatosis and insulin sensitivity in Western diet-fed mice.American journal of physiology. Gastrointestinal and liver physiology · 2019Article
- Bile Acid Receptors and Gastrointestinal Functions.Liver research (Beijing, China) · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimTGR5 agonists stimulate intestinal glucagon-like peptide-1 (GLP-1) release, but systemic exposure causes unwanted side effects, such as gallbladder filling. In the present study, linagliptin, a DPP-4 inhibitor with a large molecular weight and polarity, and MN6, a previously described TGR5 agonist, were linked to produce OL3, a novel low-absorbed TGR5 agonist with reduced side-effects and dual function in lowering blood glucose by activation of TGR5 and inhibition of DPP-4.
methodsTGR5 activation was assayed in HEK293 cells stably expressing human or mouse TGR5 and a CRE-driven luciferase gene. DPP-4 inhibition was assessed based on the rate of hydrolysis of a surrogate substrate. GLP-1 secretion was measured in human enteroendocrine NCI-H716 cells. OL3 permeability was tested in Caco-2 cells. Acute glucose-lowering effects of OL3 were evaluated in ICR and diabetic ob/ob mice.
resultsOL3 activated human and mouse TGR5 with an EC
conclusionOL3 is a low-absorbed TGR5 agonist that lowers blood glucose without inducing gallbladder filling. This study presents a new strategy in the development of potent TGR5 agonists in treating type 2 diabetes, which target to the intestine to avoid systemic side effects.
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.