Evidence map›Paper›PMID 25377315›Full record

ArticleAmerican journal of physiology. Gastrointestinal and liver physiology2015

Glucose-dependent insulinotropic polypeptide-mediated signaling pathways enhance apical PepT1 expression in intestinal epithelial cells.

Steven D Coon, Vazhaikkurichi M Rajendran, John H Schwartz, Satish K Singh

Open access · greenAbstract read
In one paragraph

Article in American journal of physiology. Gastrointestinal and liver physiology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
0.9field-weighted citation impact, top 21% 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

9 citing papers in PubMed, 22 citations in OpenAlex.

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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

4 authors at 3 institutions in 1 country.

Steven D CoonDepartment of Medicine, Boston University School of Medicine, Boston, Massachusetts; Department of Medicine, Boston Veterans Affairs Healthcare System, Boston, Massachusetts; Department of Medicine, Boston University Clinical & Translational Science Institute, Boston, Massachusetts; and scoon@bu.edu.
Vazhaikkurichi M RajendranDepartment of Biochemistry and Molecular Biology, West Virginia University School of Medicine, Morgantown, West Virginia.
John H SchwartzDepartment of Medicine, Boston University School of Medicine, Boston, Massachusetts;
Satish K SinghDepartment of Medicine, Boston University School of Medicine, Boston, Massachusetts; Department of Medicine, Boston Veterans Affairs Healthcare System, Boston, Massachusetts;
Boston University · USVA Boston Healthcare System · USWest Virginia University · US

Funding

Boston University Clinical and Translational Science Award (CTSA) Program UL1UL1TR000157 · NCATS · BOSTON UNIVERSITY MEDICAL CAMPUS · PI CENTER, DAVID M. · 2012 to 2013
$7.9M
Role of IK channels in rat distal colonR01DK018777 · NIDDK · YALE UNIVERSITY · PI RAJENDRAN, VAZHAIKKURICHI M. · 1986 to 2010
$2.5M
Role of BK Channels in K+-driven Colonic Water Secretion in Health and DiseaseR01DK104791 · NIDDK · WEST VIRGINIA UNIVERSITY · PI RAJENDRAN, VAZHAIKKURICHI M. · 2015 to 2019
$1.7M
NCATS NIH HHS UL1 TR000157NCATS NIH HHS UL1-TR000157NIDDK NIH HHS DK-018777NIDDK NIH HHS R01 DK018777NIDDK NIH HHS R01 DK104791
6 · The paper itself

Abstract

We have shown recently that glucose-dependent insulinotropic polypeptide (GIP), but not glucagon-like peptide 1 (GLP-1) augments H(+) peptide cotransporter (PepT1)-mediated peptide absorption in murine jejunum. While we observed that inhibiting cAMP production decreased this augmentation of PepT1 activity by GIP, it was unclear whether PKA and/or other regulators of cAMP signaling pathway(s) were involved. This study utilized tritiated glycyl-sarcosine [(3)H-glycyl-sarcosine (Gly-Sar), a relatively nonhydrolyzable dipeptide] uptake to measure PepT1 activity in CDX2-transfected IEC-6 (IEC-6/CDX2) cells, an absorptive intestinal epithelial cell model. Similar to our earlier observations with mouse jejunum, GIP but not GLP-1 augmented Gly-Sar uptake (control vs. +GIP: 154 ± 22 vs. 454 ± 39 pmol/mg protein; P < 0.001) in IEC-6/CDX2 cells. Rp-cAMP (a PKA inhibitor) and wortmannin [phosophoinositide-3-kinase (PI3K) inhibitor] pretreatment completely blocked, whereas neither calphostin C (a potent PKC inhibitor) nor BAPTA (an intracellular Ca(2+) chelator) pretreatment affected the GIP-augmented Gly-Sar uptake in IEC-6/CDX2 cells. The downstream metabolites Epac (control vs. Epac agonist: 287 ± 22 vs. 711 ± 80 pmol/mg protein) and AKT (control vs. AKT inhibitor: 720 ± 50 vs. 75 ± 19 pmol/mg protein) were shown to be involved in GIP-augmented PepT1 activity as well. Western blot analyses revealed that both GIP and Epac agonist pretreatment enhance the PepT1 expression on the apical membranes, which is completely blocked by wortmannin in IEC-6/CDX2 cells. These observations demonstrate that both cAMP and PI3K signaling pathways augment GIP-induced peptide uptake through Epac and AKT-mediated pathways in intestinal epithelial cells, respectively. In addition, these observations also indicate that both Epac and AKT-mediated signaling pathways increase apical membrane expression of PepT1 in intestinal absorptive epithelial cells.

Indexed as

AnimalsCell LineCyclic AMPDipeptidesDose-Response Relationship, DrugEpithelial CellsGastric Inhibitory PolypeptideGuanine Nucleotide Exchange FactorsHomeodomain ProteinsIntestinal AbsorptionIntestinal MucosaIntestinesPeptide Transporter 1Phosphatidylinositol 3-KinasePhosphoinositide-3 Kinase InhibitorsProtein Kinase InhibitorsCyclic AMPDipeptidesGastric Inhibitory Polypeptidegastric inhibitory polypeptide receptorglycylsarcosineGuanine Nucleotide Exchange FactorsHomeodomain ProteinsPeptide Transporter 1Phosphatidylinositol 3-KinasePhosphoinositide-3 Kinase InhibitorsProtein Kinase InhibitorsProto-Oncogene Proteins c-aktRapgef3 protein, ratReceptors, Gastrointestinal HormoneSlc15a1 protein, ratSymportersCDX2 expressiondipeptide uptake Gly-Sar uptake.IEC-6 cellsIntestinal absorptive epithelial cells

Identifiers

PMID25377315
PMCPMC4281688
OpenAlexW2115145744

What OpenQuestion holds

Textmetadata
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.