Evidence map›Paper›PMID 25288806›Full record

ArticleThe Journal of biological chemistry2014

Insulin secretion induced by glucose-dependent insulinotropic polypeptide requires phosphatidylinositol 3-kinase γ in rodent and human β-cells.

Jelena Kolic, Aliya F Spigelman, Alannah M Smith, Jocelyn E Manning Fox, Patrick E MacDonald

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
2.3field-weighted citation impact, top 13% 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

12 citing papers in PubMed, 26 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. P-Rex1 Mediates Glucose-Stimulated Rac1 Activation and Insulin Secretion in Pancreatic β-Cells.Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology · 2020
    Article
  5. Article
  6. Review
  7. Article
  8. p110γ deficiency protects against pancreatic carcinogenesis yet predisposes to diet-induced hepatotoxicity.Proceedings of the National Academy of Sciences of the United States of America · 2019
    Article
  9. Article
  10. cAMP-independent effects of GLP-1 on β cells.The Journal of clinical investigation · 2015
    Article
  11. Article
  12. 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

5 authors at 1 institution in 1 country.

Jelena KolicDepartment of Pharmacology, and the Alberta Diabetes Institute, University of Alberta, Edmonton, Alberta T6G 2E1, Canada.
Aliya F SpigelmanDepartment of Pharmacology, and the Alberta Diabetes Institute, University of Alberta, Edmonton, Alberta T6G 2E1, Canada.
Alannah M SmithDepartment of Pharmacology, and the Alberta Diabetes Institute, University of Alberta, Edmonton, Alberta T6G 2E1, Canada.
Jocelyn E Manning FoxDepartment of Pharmacology, and the Alberta Diabetes Institute, University of Alberta, Edmonton, Alberta T6G 2E1, Canada.
Patrick E MacDonaldDepartment of Pharmacology, and the Alberta Diabetes Institute, University of Alberta, Edmonton, Alberta T6G 2E1, Canada. Electronic address: pmacdonald@ualberta.ca.
University of Alberta · CA

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

PI3Kγ, a G-protein-coupled type 1B phosphoinositol 3-kinase, exhibits a basal glucose-independent activity in β-cells and can be activated by the glucose-dependent insulinotropic polypeptide (GIP). We therefore investigated the role of the PI3Kγ catalytic subunit (p110γ) in insulin secretion and β-cell exocytosis stimulated by GIP. We inhibited p110γ with AS604850 (1 μmol/liter) or knocked it down using an shRNA adenovirus or siRNA duplex in mouse and human islets and β-cells. Inhibition of PI3Kγ blunted the exocytotic and insulinotropic response to GIP receptor activation, whereas responses to the glucagon-like peptide-1 or the glucagon-like peptide-1 receptor agonist exendin-4 were unchanged. Downstream, we find that GIP, much like glucose stimulation, activates the small GTPase protein Rac1 to induce actin remodeling. Inhibition of PI3Kγ blocked these effects of GIP. Although exendin-4 could also stimulate actin remodeling, this was not prevented by p110γ inhibition. Finally, forced actin depolymerization with latrunculin B restored the exocytotic and secretory responses to GIP during PI3Kγ inhibition, demonstrating that the loss of GIP-induced actin depolymerization was indeed limiting insulin exocytosis.

Indexed as

Gene Expression Regulation, EnzymologicActinsAnimalsClass Ib Phosphatidylinositol 3-KinaseDiabetes Mellitus, Type 2DioxolesElectrophysiologyExocytosisGastric Inhibitory PolypeptideGlucoseHumansInhibitory Concentration 50InsulinInsulin-Secreting CellsInsulin SecretionIslets of Langerhans5-(2,2-difluorobenzo(1,3)dioxol-5-ylmethylene)thiazolidine-2,4-dioneActinsClass Ib Phosphatidylinositol 3-KinaseDioxolesGastric Inhibitory PolypeptideGlucoseInsulinNeuropeptidesrac1 GTP-Binding ProteinRac1 protein, mouseThiazolidinedionesActinExocytosisInsulinPancreatic IsletPhosphatidylinositide 3-Kinase (PI 3-Kinase)Ras-related C3 Botulinum Toxin Substrate 1 (Rac1)Type 2 Diabetes

Identifiers

PMID25288806
PMCPMC4231687
OpenAlexW1579830893

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.