Evidence map›Paper›PMID 25205820›Full record

ArticleAmerican journal of physiology. Endocrinology and metabolism2014

Insulin secretion stimulated by L-arginine and its metabolite L-ornithine depends on Gα(i2).

Veronika Leiss, Katarina Flockerzie, Ana Novakovic, Michaela Rath, Annika Schönsiegel, Lutz Birnbaumer, Annette Schürmann, Christian Harteneck, Bernd Nürnberg

Open access · greenAbstract readComparative Study
In one paragraph

Article in American journal of physiology. Endocrinology and metabolism, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
1.5field-weighted citation impact, top 18% 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

25 citing papers in PubMed, 34 citations in OpenAlex.

  1. Article
  2. GαInternational journal of molecular sciences · 2025
    Article
  3. Article
  4. Article
  5. Targeting GαBasic research in cardiology · 2024
    Article
  6. Article
  7. Article
  8. Review
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Lack of GαMolecular metabolism · 2020
    Article
  16. Article
  17. UGGT1 retains proinsulin in the endoplasmic reticulum in an arginine dependent manner.Biochemical and biophysical research communications · 2020
    Article
  18. Selective protection of murine cerebral GJournal of molecular medicine (Berlin, Germany) · 2020
    Article
  19. Article
  20. Article
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

9 authors at 3 institutions in 2 countries.

Veronika LeissDepartment of Pharmacology and Experimental Therapy, Institute of Experimental and Clinical Pharmacology and Toxicology, Eberhard Karls University Hospitals and Clinics, and Interfaculty Center of Pharmacogenomics and Drug Research, University of Tübingen, Tübingen, Germany;
Katarina FlockerzieDepartment of Pharmacology and Experimental Therapy, Institute of Experimental and Clinical Pharmacology and Toxicology, Eberhard Karls University Hospitals and Clinics, and Interfaculty Center of Pharmacogenomics and Drug Research, University of Tübingen, Tübingen, Germany;
Ana NovakovicDepartment of Pharmacology and Experimental Therapy, Institute of Experimental and Clinical Pharmacology and Toxicology, Eberhard Karls University Hospitals and Clinics, and Interfaculty Center of Pharmacogenomics and Drug Research, University of Tübingen, Tübingen, Germany;
Michaela RathDepartment of Experimental Diabetology, German Institute of Human Nutrition, Potsdam-Rehbrücke, Nuthetal, Germany;
Annika SchönsiegelDepartment of Pharmacology and Experimental Therapy, Institute of Experimental and Clinical Pharmacology and Toxicology, Eberhard Karls University Hospitals and Clinics, and Interfaculty Center of Pharmacogenomics and Drug Research, University of Tübingen, Tübingen, Germany;
Lutz BirnbaumerLaboratory of Neurobiology, National Institute of Environmental Health Sciences, National Institutes of Health/Department of Health and Human Services, Durham, North Carolina.
Annette SchürmannDepartment of Experimental Diabetology, German Institute of Human Nutrition, Potsdam-Rehbrücke, Nuthetal, Germany;
Christian HarteneckDepartment of Pharmacology and Experimental Therapy, Institute of Experimental and Clinical Pharmacology and Toxicology, Eberhard Karls University Hospitals and Clinics, and Interfaculty Center of Pharmacogenomics and Drug Research, University of Tübingen, Tübingen, Germany;
Bernd NürnbergDepartment of Pharmacology and Experimental Therapy, Institute of Experimental and Clinical Pharmacology and Toxicology, Eberhard Karls University Hospitals and Clinics, and Interfaculty Center of Pharmacogenomics and Drug Research, University of Tübingen, Tübingen, Germany; bernd.nuernberg@uni-tuebingen.de.
University of Tübingen · DEGerman Institute of Human Nutrition · DENational Institutes of Health · US

Funding

Transmembrane Signaling Mechanisms Involving TRP ChannelsZ01ES101684 · NIEHS · NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES · PI BIRNBAUMER, LUTZ · 2003 to 2008
$2.1M
NIEHS NIH HHS Z01 ES-101684
6 · The paper itself

Abstract

Bordetella pertussis toxin (PTx), also known as islet-activating protein, induces insulin secretion by ADP-ribosylation of inhibitory G proteins. PTx-induced insulin secretion may result either from inactivation of Gα(o) proteins or from combined inactivation of Gα(o), Gα(i1), Gα(i2), and Gα(i3) isoforms. However, the specific role of Gα(i2) in pancreatic β-cells still remains unknown. In global (Gα(i2)(-/-)) and β-cell-specific (Gα(i2)(βcko)) gene-targeted Gα(i2) mouse models, we studied glucose homeostasis and islet functions. Insulin secretion experiments and intracellular Ca²⁺ measurements were used to characterize Gα(i2) function in vitro. Gα(i2)(-/-) and Gα(i2)(βcko) mice showed an unexpected metabolic phenotype, i.e., significantly lower plasma insulin levels upon intraperitoneal glucose challenge in Gα(i2)(-/-) and Gα(i2)(βcko) mice, whereas plasma glucose concentrations were unchanged in Gα(i2)(-/-) but significantly increased in Gα(i2)(βcko) mice. These findings indicate a novel albeit unexpected role for Gα(i2) in the expression, turnover, and/or release of insulin from islets. Detection of insulin secretion in isolated islets did not show differences in response to high (16 mM) glucose concentrations between control and β-cell-specific Gα(i2)-deficient mice. In contrast, the two- to threefold increase in insulin secretion evoked by L-arginine or L-ornithine (in the presence of 16 mM glucose) was significantly reduced in islets lacking Gα(i2). In accord with a reduced level of insulin secretion, intracellular calcium concentrations induced by the agonistic amino acid L-arginine did not reach control levels in β-cells. The presented analysis of gene-targeted mice provides novel insights in the role of β-cell Gα(i2) showing that amino acid-induced insulin-release depends on Gα(i2).

Indexed as

Up-RegulationAnimalsArginineBlood GlucoseCalcium SignalingCrosses, GeneticDown-RegulationFluorescent Antibody TechniqueGTP-Binding Protein alpha Subunit, Gi2GTP-Binding Protein alpha Subunits, Gi-GoHyperglycemiaHypoglycemiaInsulinInsulin SecretionIslets of LangerhansMice, Inbred C57BLArginineBlood GlucoseGnai2 protein, mouseGNAO1 protein, mouseGTP-Binding Protein alpha Subunit, Gi2GTP-Binding Protein alpha Subunits, Gi-GoInsulinOrnithineGPCRGαi2insulin secretionl-arginineβ-cell

Identifiers

PMID25205820
PMCPMC4216945
OpenAlexW2013216962

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.