ArticleThe Journal of biological chemistry2014
Insulin secretion induced by glucose-dependent insulinotropic polypeptide requires phosphatidylinositol 3-kinase γ in rodent and human β-cells.
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.
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Who cites it
12 citing papers in PubMed, 26 citations in OpenAlex.
- TMEM55A-mediated PI5P signalling regulates alpha cell actin depolymerisation and glucagon secretion.Diabetologia · 2025Article
- Ablation of PI3Kγ in neurons protects mice from diet-induced obesity MASLD and insulin resistance.iScience · 2025Article
- TMEM55A-mediated PI5P signaling regulates α-cell actin depolymerization and glucagon secretion.bioRxiv : the preprint server for biology · 2024Article
- 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 · 2020Article
- Improved glucose tolerance with DPPIV inhibition requires β-cell SENP1 amplification of glucose-stimulated insulin secretion.Physiological reports · 2020Article
- For Better or Worse: The Potential for Dose Limiting the On-Target Toxicity of PI 3-Kinase Inhibitors.Biomolecules · 2019Review
- Glucose, adrenaline and palmitate antagonistically regulate insulin and glucagon secretion in human pseudoislets.Scientific reports · 2019Article
- 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 · 2019Article
- PI3 kinases p110α and PI3K-C2β negatively regulate cAMP via PDE3/8 to control insulin secretion in mouse and human islets.Molecular metabolism · 2016Article
- cAMP-independent effects of GLP-1 on β cells.The Journal of clinical investigation · 2015Article
- Nanoscale Landscape of Phosphoinositides Revealed by Specific Pleckstrin Homology (PH) Domains Using Single-molecule Superresolution Imaging in the Plasma Membrane.The Journal of biological chemistry · 2015Article
- The gut sensor as regulator of body weight.Endocrine · 2015Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
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.
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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.