Evidence map›Paper›PMID 25792564›Full record

ArticleAmerican journal of physiology. Gastrointestinal and liver physiology2015

Glutamine and alanyl-glutamine promote crypt expansion and mTOR signaling in murine enteroids.

Sean R Moore, Marjorie M Guedes, Tie B Costa, Jefferson Vallance, Elizabeth A Maier, Kristina J Betz, Eitaro Aihara, Maxime M Mahe, Aldo A M Lima, Reinaldo B Oriá and 1 more

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 35 papers.

0numbers the graph read from it
0cells of the map it votes in
35citing papers in PubMed
3.2field-weighted citation impact, top 8% 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

35 citing papers in PubMed, 70 citations in OpenAlex.

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  10. Dietary and metabolic effects on intestinal stem cells in health and disease.Nature reviews. Gastroenterology & hepatology · 2025
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  20. Recent advances in organoid development and applications in disease modeling.Biochimica et biophysica acta. Reviews on cancer · 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

11 authors at 4 institutions in 2 countries.

Sean R MooreDivision of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, Ohio; sean.moore@cchmc.org.
Marjorie M GuedesDepartment of Physiology and Pharmacology, Clinical Research Unit and Institute of Biomedicine/Center for Global Health, Faculty of Medicine, Federal University of Ceará, Fortaleza, Ceará, Brazil;
Tie B CostaDepartment of Morphology, Clinical Research Unit and Institute of Biomedicine/Center for Global Health, Faculty of Medicine, Federal University of Ceará, Fortaleza, Ceará, Brazil;
Jefferson VallanceDivision of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, Ohio;
Elizabeth A MaierDivision of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, Ohio;
Kristina J BetzDivision of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, Ohio;
Eitaro AiharaMolecular and Cellular Physiology, University of Cincinnati College of Medicine, Cincinnati, Ohio; and.
Maxime M MaheDivision of Pediatric Surgery, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
Aldo A M LimaDepartment of Physiology and Pharmacology, Clinical Research Unit and Institute of Biomedicine/Center for Global Health, Faculty of Medicine, Federal University of Ceará, Fortaleza, Ceará, Brazil;
Reinaldo B OriáDepartment of Physiology and Pharmacology, Clinical Research Unit and Institute of Biomedicine/Center for Global Health, Faculty of Medicine, Federal University of Ceará, Fortaleza, Ceará, Brazil;
Noah F ShroyerDivision of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, Ohio;
Cincinnati Children's Hospital Medical Center · USUniversidade Federal do Ceará · BRUniversity of Cincinnati · USUniversity of Cincinnati Medical Center · US

Funding

Stem Cell/Organoid and Genome Editing CoreP30DK078392 · NIDDK · CINCINNATI CHILDRENS HOSP MED CTR · PI Theresa Alenghat · 2007 to 2026
$24.4M
Novel Platforms for Human Intestinal Enteroids: Matrix, Mechanics, and TopographyU19AI116497 · NIAID · BAYLOR COLLEGE OF MEDICINE · PI GRANDE-ALLEN, KATHRYN JANE · 2015 to 2025
$13.2M
Medical Scientist Training ProgramT32GM063483 · NIGMS · UNIVERSITY OF CINCINNATI · PI KHURANA HERSHEY, GURJIT K. · 2002 to 2022
$6.7M
KLF5 regulation of intestinal development and stem cell homeostasis.R01DK092306 · NIDDK · CINCINNATI CHILDRENS HOSP MED CTR · PI SHROYER, NOAH FREEMAN · 2011 to 2014
$1.6M
The role of ATOH1 as a tumor suppressor in colorectal cancerR01CA142826 · NCI · CINCINNATI CHILDRENS HOSP MED CTR · PI SHROYER, NOAH FREEMAN · 2010 to 2014
$1.5M
Cellular Molecular Mechanisms of Alanyl-Glutamine Oral Rehydration and NutritionK02TW008767 · FIC · CINCINNATI CHILDRENS HOSP MED CTR · PI MOORE, SEAN RYAN · 2011 to 2015
$627k
FIC NIH HHS K02 TW008767FIC NIH HHS K02 TW-08767NCI NIH HHS R01 CA-142826NCI NIH HHS R01 CA142826NIAID NIH HHS U19 AI116497NIDDK NIH HHS P30 DK-078392NIDDK NIH HHS P30 DK078392NIDDK NIH HHS R01 DK-092306NIGMS NIH HHS T32 GM063483
6 · The paper itself

Abstract

L-glutamine (Gln) is a key metabolic fuel for intestinal epithelial cell proliferation and survival and may be conditionally essential for gut homeostasis during catabolic states. We show that L-alanyl-L-glutamine (Ala-Gln), a stable Gln dipeptide, protects mice against jejunal crypt depletion in the setting of dietary protein and fat deficiency. Separately, we show that murine crypt cultures (enteroids) derived from the jejunum require Gln or Ala-Gln for maximal expansion. Once expanded, enteroids deprived of Gln display a gradual atrophy of cryptlike domains, with decreased epithelial proliferation, but stable proportions of Paneth and goblet cell differentiation, at 24 h. Replenishment of enteroid medium with Gln selectively activates mammalian target of rapamycin (mTOR) signaling pathways, rescues proliferation, and promotes crypt regeneration. Gln deprivation beyond 48 h leads to destabilization of enteroids but persistence of EGFP-Lgr5-positive intestinal stem cells with the capacity to regenerate enteroids upon Gln rescue. Collectively, these findings indicate that Gln deprivation induces a reversible quiescence of intestinal stem cells and provides new insights into nutritional regulation of intestinal epithelial homeostasis.

Indexed as

AnimalsCell DifferentiationCells, CulturedDipeptidesEpithelial CellsFemaleGlutamineIntestinal MucosaMaleMiceMice, Inbred C57BLSignal TransductionStem CellsTOR Serine-Threonine KinasesalanylglutamineDipeptidesGlutaminemTOR protein, mouseTOR Serine-Threonine KinasesERKintestinal organoidsl-alanyl-l-glutaminel-glutaminemammalian target of rapamycin

Identifiers

PMID25792564
PMCPMC4437023
OpenAlexW2135456321

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.