Evidence map›Paper›PMID 20977906›Full record

ArticleGastroenterology2011

D-glucose acts via sodium/glucose cotransporter 1 to increase NHE3 in mouse jejunal brush border by a Na+/H+ exchange regulatory factor 2-dependent process.

Rong Lin, Rakhilya Murtazina, Boyoung Cha, Molee Chakraborty, Rafiquel Sarker, Tian-E Chen, Zhihong Lin, Boris M Hogema, Hugo R de Jonge, Ursula Seidler and 4 more

Open access · bronzeAbstract read
In one paragraph

Article in Gastroenterology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.

0numbers the graph read from it
0cells of the map it votes in
54citing papers in PubMed
6.5field-weighted citation impact, top 3% 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

54 citing papers in PubMed, 96 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Article
  5. Inhibition of protein kinase C-α and activation of ezrin byAmerican journal of physiology. Endocrinology and metabolism · 2023
    Article
  6. Article
  7. Review
  8. Metformin Inhibits NaFrontiers in physiology · 2022
    Article
  9. Expert opinion on therapeutic targets · 2021
    Article
  10. Article
  11. Review
  12. A role for tubular NaAmerican journal of physiology. Renal physiology · 2020
    Article
  13. Review
  14. Review
  15. Review
  16. NaInternational journal of molecular sciences · 2020
    Article
  17. Article
  18. Article
  19. The Role of Ion Transporters in the Pathophysiology of Infectious Diarrhea.Cellular and molecular gastroenterology and hepatology · 2018
    Review
  20. Review
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

14 authors at 6 institutions in 4 countries.

Rong LinDepartment of Medicine, Division of Gastroenterology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Rakhilya Murtazina
Boyoung Cha
Molee Chakraborty
Rafiquel Sarker
Tian-E Chen
Zhihong Lin
Boris M Hogema
Hugo R de Jonge
Ursula Seidler
Jerrold R Turner
Xuhang Li
Olga Kovbasnjuk
Mark Donowitz
Johns Hopkins Medicine · USJohns Hopkins University · USErasmus MC · NLMedizinische Hochschule Hannover · DEUniversity of Chicago · USWuhan Union Hospital · CN

Funding

Two-Photon Microscopy Imaging CoreP01DK072084 · NIDDK · JOHNS HOPKINS UNIVERSITY · PI DONOWITZ, MARK · 2006 to 2013
$12.7M
DIARRHEAL DISEASES: A PHYSIOLOGIC APPROACH TO TREATMENTR01DK026523 · NIDDK · TUFTS MEDICAL CENTER · PI DONOWITZ, MARK · 1986 to 2016
$7.8M
PDZ Domain Proteins and NHE3 RegulationR01DK061765 · NIDDK · JOHNS HOPKINS UNIVERSITY · PI DONOWITZ, MARK, TSE, CHUNG-MING · 2004 to 2013
$4.7M
Hopkins Digestive Diseases Research Development CenterR24DK064388 · NIDDK · JOHNS HOPKINS UNIVERSITY · PI DONOWITZ, MARK · 2003 to 2010
$4.6M
STRUCTURE AND FUNCTION STUDIES OF CLONED SODIUM AND HYDROGEN EXCHANGERSP01DK044484 · NIDDK · JOHNS HOPKINS UNIVERSITY · PI MONTROSE, MARSHALL H · 1992 to 2002
$2.6M
NIDDK NIH HHS P01 DK044484NIDDK NIH HHS P01 DK072084NIDDK NIH HHS P01-DK72084NIDDK NIH HHS R01 DK026523NIDDK NIH HHS R01 DK061765NIDDK NIH HHS R01-DK26523NIDDK NIH HHS R01-DK61765NIDDK NIH HHS R24 DK064388NIDDK NIH HHS R24-DK64388
6 · The paper itself

Abstract

BACKGROUND &

aimsOral rehydration solutions reduce diarrhea-associated mortality. Stimulated sodium absorption by these solutions is mediated by the Na(+)/H(+) hydrogen exchanger NHE3 and is increased by Na(+)-glucose co-transport in vitro, but the mechanisms of this up-regulated process are only partially understood.

methodsIntracellular pH was measured in jejunal enterocytes of wild-type mice and mice with disrupted Na+/H+ exchange regulatory co-factor 2 (NHERF2-/- mice) by multiphoton microscopy. Diarrhea was induced by cholera toxin. Caco-2BBe cells that express NHE3 and the sodium/glucose cotransporter 1 (SGLT1) were studied by fluorometry, before and after siRNA-mediated knockdown of NHERF1 or NHERF2. NHE3 distribution was assessed by cell-surface biotinylation and confocal microscopy. Brush-border mobility was determined by fluorescence recovery after photobleaching and confocal microscopy.

resultsThe nonmetabolized SGLT1 substrate α-methyl-D-Glu (α-MD-G) activated jejunal NHE3; this process required Akt and NHERF2. α-MD-G normalized NHE3 activity after cholera toxin-induced diarrhea. α-MD-G-stimulated jejunal NHE3 activity was defective in NHERF2-/- mice and cells with NHERF2 knockdown, but occurred normally with NHERF1 knockdown; was associated with increased NHE3 surface expression in Caco-2 cells, which also was NHERF2-dependent; was associated with dissociation of NHE3 from NHERF2 and an increase in the NHE3 mobile fraction from the brush border; and was accompanied by a NHERF2 ezrin-radixin-moesin-binding domain-dependent increase in co-precipitation of ezrin with NHE3.

conclusionsSGLT1-mediated Na-glucose co-transport stimulates NHE3 activity in vivo by an Akt- and NHERF2-dependent signaling pathway. It is associated with increased brush-border NHE3 and association between ezrin and NHE3. Activation of NHE3 corrects cholera toxin-induced defects in Na absorption and might contribute to the efficacy of oral rehydration solutions.

Indexed as

Fluid TherapyAnimalsCaco-2 CellsCholera ToxinCytoskeletal ProteinsDiarrheaEzrinGlucoseHumansIntestinal AbsorptionJejunumMaleMethylglucosidesMiceMice, Inbred C57BLMicrovilliCholera ToxinCytoskeletal ProteinsEzrinGlucosemethylglucosideMethylglucosidesPhosphoproteinsProto-Oncogene Proteins c-aktRNA, Small InterferingSLC9A3 protein, humanSlc9a3 protein, mouseSodiumSodium-Glucose Transporter 1Sodium-Hydrogen Exchanger 3sodium-hydrogen exchanger regulatory factorSodium-Hydrogen Exchangers

Identifiers

PMID20977906
PMCPMC3031713
OpenAlexW1983388632

What Socratic 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 Socratic graph.