Evidence map›Paper›PMID 21276423›Full record

ArticleBiochemical pharmacology2011

Arf nucleotide binding site opener [ARNO] promotes sequential activation of Arf6, Cdc42 and Rac1 and insulin secretion in INS 832/13 β-cells and rat islets.

Bhavaani Jayaram, Ismail Syed, Chandrashekara N Kyathanahalli, Christopher J Rhodes, Anjaneyulu Kowluru

Abstract read
In one paragraph

Article in Biochemical pharmacology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.

0numbers the graph read from it
0cells of the map it votes in
39citing papers in PubMed
5.9field-weighted citation impact, top 4% 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

39 citing papers in PubMed, 55 citations in OpenAlex.

  1. Trial
  2. Article
  3. Review
  4. Article
  5. Review
  6. Novel Roles for Geranylgeranyl Transferase-III (GGTase-III) in Insulin Secretion.Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology · 2025
    Article
  7. Article
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  9. Review
  10. Review
  11. Article
  12. Article
  13. Review
  14. RhoG-Rac1 Signaling Pathway Mediates Metabolic Dysfunction of the Pancreatic Beta-Cells Under Chronic Hyperglycemic Conditions.Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology · 2021
    Article
  15. Article
  16. Review
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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

5 authors at 3 institutions in 1 country.

Bhavaani JayaramDepartment of Pharmaceutical Sciences, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University and β-Cell Biochemistry Laboratory, John D. Dingell VA Medical Center, 259 Mack Avenue, Detroit, MI 48201, USA.
Ismail Syed
Chandrashekara N Kyathanahalli
Christopher J Rhodes
Anjaneyulu Kowluru
John D. Dingell VA Medical Center · USWayne State University · USUniversity of Chicago · US

Funding

MITOGENIC SIGNAL TRANSDUCTION IN PANCREATIC BETA CELLSR01DK055267 · NIDDK · UNIVERSITY OF TEXAS SW MED CTR/DALLAS · PI RHODES, CHRISTOPHER J · 1998 to 2013
$4.3M
Protein Prenyltransferases in Glucose-Stimulated Insulin SecretionR01DK074921 · NIDDK · WAYNE STATE UNIVERSITY · PI KOWLURU, ANJANEYULU · 2007 to 2010
$1.0M
NIDDK NIH HHS DK 74921NIDDK NIH HHS R01 DK055267NIDDK NIH HHS R01 DK074921
6 · The paper itself

Abstract

Glucose-stimulated insulin secretion [GSIS] involves interplay between small G-proteins and their regulatory factors. Herein, we tested the hypothesis that Arf nucleotide binding site opener [ARNO], a guanine nucleotide-exchange factor [GEF] for the small G-protein Arf6, mediates the functional activation of Arf6, and that ARNO/Arf6 signaling axis, in turn, controls the activation of Cdc42 and Rac1, which have been implicated in GSIS. Molecular biological [i.e., expression of inactive mutants or siRNA] and pharmacological approaches were employed to assess the roles for ARNO/Arf6 signaling pathway in insulin secretion in normal rat islets and INS 832/13 cells. Degrees of activation of Arf6 and Cdc42/Rac1 were quantitated by GST-GGA3 and PAK-1 kinase pull-down assays, respectively. ARNO is expressed in INS 832/13 cells, rat islets and human islets. Expression of inactive mutants of Arf6 [Arf6-T27N] or ARNO [ARNO-E156K] or siRNA-ARNO markedly reduced GSIS in isolated β-cells. SecinH3, a selective inhibitor of ARNO/Arf6 signaling axis, also inhibited GSIS in INS 832/13 cells and rat islets. Stimulatory concentrations of glucose promoted Arf6 activation, which was inhibited by secinH3 or siRNA-ARNO, suggesting that ARNO/Arf6 signaling cascade is necessary for GSIS. SecinH3 or siRNA-ARNO also inhibited glucose-induced activation of Cdc42 and Rac1 suggesting that ARNO/Arf6 might be upstream to Cdc42 and Rac1 activation steps, which are necessary for GSIS. Lastly, co-immunoprecipitation and confocal microscopic studies suggested increased association between Arf6 and ARNO in glucose-stimulated β-cells. These findings provide the first evidence to implicate ARNO in the sequential activation of Arf6, Cdc42 and Rac1 culminating in GSIS.

Indexed as

ADP-Ribosylation Factor 6ADP-Ribosylation FactorsAnimalscdc42 GTP-Binding ProteinCell Culture TechniquesCell LineFluorescent Antibody TechniqueGlucoseGTPase-Activating ProteinsHumansHydrophobic and Hydrophilic InteractionsImmunoprecipitationInsulinInsulin-Secreting CellsInsulin SecretionIslets of LangerhansADP-Ribosylation Factor 6ADP-Ribosylation FactorsARF6 protein, humanArf6 protein, ratcdc42 GTP-Binding Proteincytohesin-2GlucoseGTPase-Activating ProteinsInsulinrac1 GTP-Binding ProteinRac1 protein, ratRNA, Small Interfering

Identifiers

PMID21276423
PMCPMC3073812
OpenAlexW2059050609

What OpenQuestion holds

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Registered trials

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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.