ArticleThe Journal of cell biology2022
VAMP4 regulates insulin levels by targeting secretory granules to lysosomes.
Article in The Journal of cell biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 18 citations in OpenAlex.
- SARS-CoV-2 seeds IAPP aggregation and β-cell failure.Signal transduction and targeted therapy · 2026Article
- From Disposal to Display: Crinophagy as a β-Cell Source of Neoantigens in Type 1 Diabetes.Immunological reviews · 2026Review
- Crinophagy in Pancreatic Beta Cells: From Insulin Granule Turnover to Diabetes Pathogenesis.Pathophysiology : the official journal of the International Society for Pathophysiology · 2026Review
- Cell type-specific expression and subcellular localization of the human insulin upstream open reading frame (INSU) protein in pancreatic β-cells.The Journal of biological chemistry · 2026Article
- Dielectrophoresis reveals stimulus-induced remodeling of insulin granule subpopulations.Biophysical journal · 2026Article
- Targeting VAMPs in Aging-Related Diseases: From Mechanisms to Pharmacotherapy.Pharmaceutical research · 2026Review
- Epigenetic analyses suggest different pathways during pregnancy for development of type 1 diabetes in children with high versus low-neutral human leukocyte antigen-risk.Journal of internal medicine · 2026Article
- VAMP4/STX8 Mediate the Autophagic Secretion of Mitochondria and Promote TAMs Polarization in HNSCC.Journal of extracellular vesicles · 2026Article
- VAMP4 in hypoxic adipose stem cell exosomes alleviates ischemia-reperfusion injury.Cellular and molecular life sciences : CMLS · 2025Article
- Dielectrophoresis Reveals Stimulus-Induced Remodeling of Insulin Granule Subpopulations.bioRxiv : the preprint server for biology · 2025Article
- Millimeter-Wave Directed Energy-Mediated Neural Cell Injury: Insights into Protein Degradation and Cell Injury Mechanisms.Research square · 2025Article
- Molecular requirements for mammalian crinophagy highlight a key role for CaResearch square · 2025Article
- Article
- Autophagy-lysosome pathway in insulin & glucagon homeostasis.Frontiers in endocrinology · 2025Review
- Spatiotemporal proteomics reveals the biosynthetic lysosomal membrane protein interactome in neurons.Nature communications · 2024Article
- Inceptor binds to and directs insulin towards lysosomal degradation in β cells.Nature metabolism · 2024Article
- Optimized Proteomic Analysis of Insulin Granules From MIN6 Cells Identifies Scamp3, a Novel Regulator of Insulin Secretion and Content.Diabetes · 2024Article
- Crinophagic granules in pancreatic β cells contribute to mouse autoimmune diabetes by diversifying pathogenic epitope repertoire.Nature communications · 2024Article
- The Ykt6-Snap29-Syx13 SNARE complex promotes crinophagy via secretory granule fusion with Lamp1 carrier vesicles.Scientific reports · 2024Article
- Identifying target ion channel-related genes to construct a diagnosis model for insulinoma.Frontiers in genetics · 2023Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Insulin levels are essential for the maintenance of glucose homeostasis, and deviations lead to pathoglycemia or diabetes. However, the metabolic mechanism controlling insulin quantity and quality is poorly understood. In pancreatic β cells, insulin homeostasis and release are tightly governed by insulin secretory granule (ISG) trafficking, but the required regulators and mechanisms are largely unknown. Here, we identified that VAMP4 controlled the insulin levels in response to glucose challenge. VAMP4 deficiency led to increased blood insulin levels and hyperresponsiveness to glucose. In β cells, VAMP4 is packaged into immature ISGs (iISGs) at trans-Golgi networks and subsequently resorted to clathrin-coated vesicles during granule maturation. VAMP4-positive iISGs and resorted vesicles then fuse with lysosomes facilitated by a SNARE complex consisting of VAMP4, STX7, STX8, and VTI1B, which ensures the breakdown of excess (pro)insulin and obsolete materials and thus maintenance of intracellular insulin homeostasis. Thus, VAMP4 is a key factor regulating the insulin levels and a potential target for the treatment of diabetes.
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Registered trials
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.