Evidence map›Paper›PMID 27208775›Full record

ArticleBiochemical and biophysical research communications2016

A bitter pill for type 2 diabetes? The activation of bitter taste receptor TAS2R38 can stimulate GLP-1 release from enteroendocrine L-cells.

Hung Pham, Hongxiang Hui, Susan Morvaridi, Jiena Cai, Sanqi Zhang, Jun Tan, Vincent Wu, Nancy Levin, Beatrice Knudsen, William A Goddard and 2 more

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Biochemical and biophysical research communications, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed
3.0field-weighted citation impact, top 10% of its field
1 · What the graph read from 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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

26 citing papers in PubMed, 66 citations in OpenAlex.

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  7. Bitter taste receptors as sensors of gut luminal contents.Nature reviews. Gastroenterology & hepatology · 2025
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  18. An update on extra-oral bitter taste receptors.Journal of translational medicine · 2021
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors at 6 institutions in 2 countries.

Hung PhamDepartments of Biomedical Sciences and Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Hongxiang HuiDavid Geffen School of Medicine, University of California, Los Angeles, CA, USA; International Center for Metabolic Diseases, Southern Medical University, Guangzhou, China.
Susan MorvaridiDepartments of Biomedical Sciences and Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Jiena CaiInternational Center for Metabolic Diseases, Southern Medical University, Guangzhou, China.
Sanqi ZhangDepartment of Medicinal Chemistry, Xi'an Jiaotong University, 710061, China.
Jun TanMaterials and Process Simulation Center, California Institute of Technology, Pasadena, CA, USA; Key Laboratory of Biorheological Science and Technology, Ministry of Education, Bioengineering College, Chongqing University, Chongqing, 400030, China.
Vincent WuVeterans Affairs Greater Los Angeles Healthcare System, University of California, Los Angeles, CA, USA.
Nancy LevinGIRx Metabolics Inc., Los Angeles, CA, USA.
Beatrice KnudsenDepartments of Biomedical Sciences and Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA; David Geffen School of Medicine, University of California, Los Angeles, CA, USA.
William A GoddardMaterials and Process Simulation Center, California Institute of Technology, Pasadena, CA, USA.
Stephen J PandolDepartments of Biomedical Sciences and Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA; David Geffen School of Medicine, University of California, Los Angeles, CA, USA; Veterans Affairs Greater Los Angeles Healthcare System, University of California, Los Angeles, CA, USA; GIRx Metabolics Inc., Los Angeles, CA, USA.
Ravinder AbrolDepartments of Biomedical Sciences and Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA; David Geffen School of Medicine, University of California, Los Angeles, CA, USA; Materials and Process Simulation Center, California Institute of Technology, Pasadena, CA, USA; GIRx Metabolics Inc., Los Angeles, CA, USA. Electronic address: abrolr@csmc.edu.
Cedars-Sinai Medical Center · USCalifornia Institute of Technology · USVA Greater Los Angeles Healthcare System · USSouthern Medical University · CNUniversity of California, Los Angeles · USXi'an Jiaotong University · CN

Funding

Targeting diet-induced promotion of Kras-initiated pancreatic adenocarcinomaP01CA163200 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI PANDOL, STEPHEN J. · 2012 to 2016
$6.2M
UCLA Center for Excellence in Pancreatic DiseasesP01AT003960 · NCCIH · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI HINES, OSCAR JOE · 2007 to 2011
$5.6M
NCCIH NIH HHS P01 AT003960NCI NIH HHS P01 CA163200
6 · The paper itself

Abstract

The bitter taste receptor TAS2R38 is a G protein coupled receptor (GPCR) that has been found in many extra-oral locations like the gastrointestinal (GI) system, respiratory system, and brain, though its function at these locations is only beginning to be understood. To probe the receptor's potential metabolic role, immunohistochemistry of human ileum tissues was performed, which showed that the receptor was co-localized with glucagon-like peptide 1 (GLP-1) in L-cells. In a previous study, we had modeled the structure of this receptor for its many taste-variant haplotypes (Tan et al. 2011), including the taster haplotype PAV. The structure of this haplotype was then used in a virtual ligand screening pipeline using a collection of ∼2.5 million purchasable molecules from the ZINC database. Three compounds (Z7, Z3, Z1) were purchased from the top hits and tested along with PTU (known TAS2R38 agonist) in in vitro and in vivo assays. The dose-response study of the effect of PTU and Z7 on GLP-1 release using wild-type and TAS2R38 knockout HuTu-80 cells showed that the receptor TAS2R38 plays a major role in GLP-1 release due to these molecules. In vivo studies of PTU and the three compounds showed that they each increase GLP-1 release. PTU was also chemical linked to cellulose to slow its absorption and when tested in vivo, it showed an enhanced and prolonged GLP-1 release. These results suggest that the GI lumen location of TAS2R38 on the L-cell makes it a relatively safe drug target as systemic absorption is not needed for a TAS2R38 agonist drug to effect GLP-1 release.

Indexed as

AnimalsCell LineDiabetes Mellitus, Type 2Enteroendocrine CellsGlucagon-Like Peptide 1HumansLigandsMaleMice, Inbred BALB CMolecular Targeted TherapyReceptors, G-Protein-CoupledTaste Receptors, Type 2Glucagon-Like Peptide 1LigandsReceptors, G-Protein-CoupledTaste Receptors, Type 2DiabetesEnteroendocrine L-cellGLP-1GPCR structure predictionGut receptorsVirtual ligand screening

Identifiers

PMID27208775
PMCPMC4918516
OpenAlexW2396234369

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

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.