ArticleLife sciences2024
Pancreatic β cell derived extracellular vesicles containing surface preproinsulin are involved in glucose stimulated insulin secretion.
Article in Life sciences, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 6 citations in OpenAlex.
- GLP-1 Receptor Agonists as Molecular Relievers of Lipotoxic Stress: From Pancreatic Beta-Cell Cholesterol Efflux to Systemic and Tissue-Specific Metabolic Protection.International journal of molecular sciences · 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
- Sensing and Communicating β-Cell Stress in the Context of T1D Etiology: New Opportunities for Therapeutic Impact.Comprehensive Physiology · 2026Review
- Ser423-phosphorylated MECP2 (MECP2-pS423) accumulates in human brain, cerebrospinal fluid and serum in sporadic Alzheimer's disease.Acta neuropathologica · 2026Article
- Look Who Is Talking: Extracellular Vesicles as Mediators of Intercellular and Interorgan Communication.Comprehensive Physiology · 2026Review
- Article
- Harnessing exosomal long non-coding RNAs as a new frontier for molecular diagnostics and therapeutics in diabetes mellitus.Cell communication and signaling : CCS · 2026Review
- Extracellular vesicles from cytokine-treated human pancreatic ductal cells enhance HLA class I expression in beta cells.Frontiers in immunology · 2026Article
- β-Cell-Derived Extracellular Vesicles Boost β-Cell Functionality in Human Pancreatic Islets.Biomaterials research · 2026Article
- Review
- Pancreatic β-cells package double C2-like domain beta protein into extracellular vesicles via tandem C2 domains.Frontiers in endocrinology · 2024Article
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
aimsExtracellular vesicles (EVs) are involved in intercellular communication and are a topic of increasing interest due to their therapeutic potential. The aim of this study was to determine whether human islet-derived EVs contain insulin, and if so, what role do they play in glucose stimulated insulin secretion. MAIN
methodsWe isolated EVs from human islets culture and plasma to probe for insulin. Plasma from hyperglycemic glucose clamp experiments were also used to isolate and measure EV insulin content in response to a secretory stimulus. We performed immunogold electron microscopy for insulin presence in EVs. Co-culture experiments of isolated EVs with fresh islets were performed to examine the effect of EV cargo on insulin receptor signaling. KEY
findingsEVs isolated from culture medium contained insulin. Glucose treatment of islets increased the level of EV insulin. Hyperglycemic glucose clamp experiments in humans also lead to increased levels of insulin in plasma-derived EVs. Immunogold electron microscopy and proteinase K-digestion experiments demonstrated that insulin in EVs predominantly associated with the exterior surface of EVs while western blot analyses uncovered the presence of only preproinsulin in EVs. Membrane-bound preproinsulin in EVs was capable of activating insulin signaling pathway in an insulin receptor-dependent manner. The physiological relevance of this finding was observed in priming of human naïve islets by EVs during glucose stimulated insulin secretion. SIGNIFICANCE: Our data suggest that (1) human islets secret insulin via an alternate pathway (EV-mediated) other than conventional granule-mediated insulin secretion, and (2) EV membrane bound preproinsulin is biologically active.
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