ArticleProceedings of the National Academy of Sciences of the United States of America2003
ADP-ribosylation factor 6 regulates insulin secretion through plasma membrane phosphatidylinositol 4,5-bisphosphate.
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 52 papers.
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Who cites it
52 citing papers in PubMed, 100 citations in OpenAlex.
- Evolutionary history of disease-susceptibility loci identified in longitudinal exome-wide association studies.Molecular genetics & genomic medicine · 2019Trial
- The Potential Target Value of ADP-Ribosylation Factor 6 in Insulin Secretion Regulation and the Treatment of Metabolic Disorders.Metabolites · 2026Review
- Tissue-specific targeting of the ARF6 signalling axis for type 2 diabetes and obesity: From mechanism to nanodelivery.Clinical and translational medicine · 2026Review
- Functional genomics reveals mediators of beta cell survival in ER stress and type 2 diabetes risk.bioRxiv : the preprint server for biology · 2026Article
- Mechanism of the Regulation of Plasma Cholesterol Levels by PI(4,5)PAdvances in experimental medicine and biology · 2023Article
- Novel roles of mTORC2 in regulation of insulin secretion by actin filament remodeling.American journal of physiology. Endocrinology and metabolism · 2022Article
- Deep Resequencing of 9 Candidate Genes Identifies a Role for ARAP1 and IGF2BP2 in Modulating Insulin Secretion Adjusted for Insulin Resistance in Obese Southern Europeans.International journal of molecular sciences · 2022Article
- CARD9 mediates glucose-stimulated insulin secretion in pancreatic beta cells.Biochemical pharmacology · 2021Article
- Review
- Ubiquitination-Dependent Regulation of Small GTPases in Membrane Trafficking: From Cell Biology to Human Diseases.Frontiers in cell and developmental biology · 2021Review
- BIG1 controls macrophage pro-inflammatory responses through ARF3-mediated PI(4,5)P2 synthesis.Cell death & disease · 2020Article
- GPCRs, G Proteins, and Their Impact on β-cell Function.Comprehensive Physiology · 2020Review
- Quantitative proteomics reveals novel interaction partners of Rac1 in pancreatic β-cells: Evidence for increased interaction with Rac1 under hyperglycemic conditions.Molecular and cellular endocrinology · 2019Article
- Cellular and subcellular localization of ADP-ribosylation factor 6 in mouse peripheral tissues.Histochemistry and cell biology · 2017Article
- Decreased STARD10 Expression Is Associated with Defective Insulin Secretion in Humans and Mice.American journal of human genetics · 2017Article
- Ral-Arf6 crosstalk regulates Ral dependent exocyst trafficking and anchorage independent growth signalling.Cellular signalling · 2016Article
- Ultrastructural Localization of Endogenous Exchange Factor for ARF6 in Adrenocortical Cells In Situ of Mice.Acta histochemica et cytochemica · 2016Article
- Phosphoinositide signalling in type 2 diabetes: a β-cell perspective.Biochemical Society transactions · 2016Review
- VAV2, a guanine nucleotide exchange factor for Rac1, regulates glucose-stimulated insulin secretion in pancreatic beta cells.Diabetologia · 2015Article
- An integrative systems genetics approach reveals potential causal genes and pathways related to obesity.Genome medicine · 2015Article
Corrections and comments
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Authors and funding
2 authors at 2 institutions in 1 country.
Funding
Abstract
ADP-ribosylation factor 6 (ARF6) is a small GTP-binding protein that regulates peripheral vesicular trafficking and actin cytoskeletal dynamics, and it has been implicated as critical to regulated secretion. Expression of a dominant-inhibitory ARF6 mutant, ARF6(T27N), impaired glucose-, depolarization-, and gamma-thio-GTP-stimulated insulin secretion in the pancreatic beta cell line, MIN6. In response to depolarization, MIN6 cells expressing ARF6(T27N) displayed an unaltered initial fast phase but an impaired subsequent slow phase of insulin secretion. Actin cytoskeletal disassembly with latrunculin A enhanced insulin secretion, whereas stabilization with jasplakinolide inhibited secretion, consistent with the actin cytoskeleton serving as a barrier to exocytosis in these cells. ARF6(T27N) led to a depolarization-dependent reduction in the levels of phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] with a time course that paralleled the inhibition of secretion. Moreover, blockade of PI(4,5)P2-dependent events by expression of a lipid-binding protein resulted in inhibition of depolarization-induced secretion in a manner identical to ARF6(T27N). These results indicate that ARF6 is required to sustain adequate levels of PI(4,5)P2 during periods of increased PI(4,5)P2 metabolism such as regulated secretion.
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