ArticleProceedings of the National Academy of Sciences of the United States of America2003
Phosphatidylinositol 4-kinase serves as a metabolic sensor and regulates priming of secretory granules in pancreatic beta cells.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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Who cites it
50 citing papers in PubMed, 102 citations in OpenAlex.
- Phosphatidylinositol-4-phosphate signaling regulates dense granule biogenesis and maturation in Toxoplasma gondii.PLoS pathogens · 2026Article
- The exocytosis regulator complexin controls spontaneous synaptic vesicle release in a CAPS-dependent manner at C. elegans excitatory synapses.PLoS biology · 2025Article
- Roles for diacylglycerol in synaptic vesicle priming and release revealed by complete reconstitution of core protein machinery.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Novel Roles for Diacylglycerol in Synaptic Vesicle Priming and Release Revealed by Complete Reconstitution of Core Protein Machinery.bioRxiv : the preprint server for biology · 2023Article
- Mechanism of the Regulation of Plasma Cholesterol Levels by PI(4,5)PAdvances in experimental medicine and biology · 2023Article
- Insulin granule biogenesis and exocytosis.Cellular and molecular life sciences : CMLS · 2021Review
- Proteomic Analysis of Tear Film Obtained from Diabetic Dogs.Animals : an open access journal from MDPI · 2020Article
- Phosphatidylinositol-4,5-Biphosphate (PI(4,5)PBioMed research international · 2020Article
- Enteroviral infections in the pathogenesis of type 1 diabetes: new insights for therapeutic intervention.Current opinion in pharmacology · 2018Review
- PI4KIIα regulates insulin secretion and glucose homeostasis via a PKD-dependent pathway.Biophysics reports · 2018Article
- Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men.Physiological reviews · 2018Review
- Phosphoinositide signalling in type 2 diabetes: a β-cell perspective.Biochemical Society transactions · 2016Review
- Phospholipase Cη2 Activation Redirects Vesicle Trafficking by Regulating F-actin.The Journal of biological chemistry · 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
- PI(4,5)P₂-binding effector proteins for vesicle exocytosis.Biochimica et biophysica acta · 2015Review
- Phosphoinositides: Key modulators of energy metabolism.Biochimica et biophysica acta · 2015Review
- Phosphatidylinositol 4,5-biphosphate (PIP2) modulates interaction of syntaxin-1A with sulfonylurea receptor 1 to regulate pancreatic β-cell ATP-sensitive potassium channels.The Journal of biological chemistry · 2014Article
- CAPS and Munc13 utilize distinct PIP2-linked mechanisms to promote vesicle exocytosis.Molecular biology of the cell · 2014Article
- CAPS and Munc13: CATCHRs that SNARE Vesicles.Frontiers in endocrinology · 2013Review
- Phosphoinositides: tiny lipids with giant impact on cell regulation.Physiological reviews · 2013Review
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 2 countries.
Funding
Abstract
Insulin secretion is controlled by the beta cell's metabolic state, and the ability of the secretory granules to undergo exocytosis increases during glucose stimulation in a membrane potential-independent fashion. Here, we demonstrate that exocytosis of insulin-containing secretory granules depends on phosphatidylinositol 4-kinase (PI 4-kinase) activity and that inhibition of this enzyme suppresses glucose-stimulated insulin secretion. Intracellular application of phosphatidylinositol 4-phosphate and phosphatidylinositol 4,5-bisphosphate [PI(4,5)P(2)] stimulated exocytosis by promoting the priming of secretory granules for release and increasing the number of granules residing in a readily releasable pool. Reducing the cytoplasmic ADP concentration in a way mimicking the effects of glucose stimulation activated PI 4-kinase and increased exocytosis whereas changes of the ATP concentration in the physiological range had little effect. The PI(4,5)P(2)-binding protein Ca(2+)-dependent activator protein for secretion (CAPS) is present in beta cells, and neutralization of the protein abolished both Ca(2+)- and PI(4,5)P(2)-induced exocytosis. We conclude that ADP-induced changes in PI 4-kinase activity, via generation of PI(4,5)P(2), represents a metabolic sensor in the beta cell by virtue of its capacity to regulate the release competence of the secretory granules.
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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.