ArticleThe Journal of biological chemistry2020
A fluorescent timer reporter enables sorting of insulin secretory granules by age.
Article in The Journal of biological chemistry, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed.
- Nutrient and non-nutrient regulators of insulin secretion.Nature reviews. Endocrinology · 2026Review
- The comparative cell physiology of stem cell-derived and primary human β cells.Nature reviews. Endocrinology · 2026Review
- Classifying biophysical subpopulations of insulin secretory granules using quantitative whole-cell structure analysis.Structure (London, England : 1993) · 2026Article
- Dielectrophoresis reveals stimulus-induced remodeling of insulin granule subpopulations.Biophysical journal · 2026Article
- Integrated biophysical and spatial remodeling during insulin secretory granule maturation at the mitochondrial network.bioRxiv : the preprint server for biology · 2026Article
- Roles of molecular motors in insulin-secreting beta cells.Current opinion in cell biology · 2025Review
- Secretory stimuli distinctly regulate insulin secretory granule maturation through structural remodeling.Structure (London, England : 1993) · 2025Article
- Dielectrophoresis Reveals Stimulus-Induced Remodeling of Insulin Granule Subpopulations.bioRxiv : the preprint server for biology · 2025Article
- Classifying Biophysical Subpopulations of Insulin Secretory Granules using Quantitative Whole Cell Structure Analysis.bioRxiv : the preprint server for biology · 2025Article
- Molecular requirements for mammalian crinophagy highlight a key role for CaResearch square · 2025Article
- Machine learning-assisted decoding of temporal transcriptional dynamics via fluorescent timer.Nature communications · 2025Article
- Peptidylglycine alpha-amidating monooxygenase is important in mice for beta-cell cilia formation and insulin secretion but promotes diabetes risk through beta-cell independent mechanisms.Molecular metabolism · 2025Article
- Biphasic glucose-stimulated insulin secretion over decades: a journey from measurements and modeling to mechanistic insights.Life metabolism · 2025Review
- Early Postpartum Metabolic Heterogeneity Among Women Who Progressed to Type 2 Diabetes After Gestational Diabetes: A Prospective Cohort.Diabetes/metabolism research and reviews · 2025Article
- Optimized Proteomic Analysis of Insulin Granules From MIN6 Cells Identifies Scamp3, a Novel Regulator of Insulin Secretion and Content.Diabetes · 2024Article
- Decoding Insulin Secretory Granule Maturation Using Genetically Encoded pH Sensors.ACS sensors · 2024Article
- Organelle landscape analysis using a multiparametric particle-based method.PLoS biology · 2024Article
- Article
- The metabolic consequences of 'yo-yo' dieting are markedly influenced by genetic diversity.International journal of obesity (2005) · 2024Article
- The insulin secretory granule is a hotspot for autoantigen formation in type 1 diabetes.Diabetologia · 2024Review
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11 authors.
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No grant is acknowledged in the PubMed record.
Abstract
Within the pancreatic β-cells, insulin secretory granules (SGs) exist in functionally distinct pools, displaying variations in motility as well as docking and fusion capability. Current therapies that increase insulin secretion do not consider the existence of these distinct SG pools. Accordingly, these approaches are effective only for a short period, with a worsening of glycemia associated with continued decline in β-cell function. Insulin granule age is underappreciated as a determinant for why an insulin granule is selected for secretion and may explain why newly synthesized insulin is preferentially secreted from β-cells. Here, using a novel fluorescent timer protein, we aimed to investigate the preferential secretion model of insulin secretion and identify how granule aging is affected by variation in the β-cell environment, such as hyperglycemia. We demonstrate the use of a fluorescent timer construct, syncollin-dsRedE5TIMER, which changes its fluorescence from green to red over 18 h, in both microscopy and fluorescence-assisted organelle-sorting techniques. We confirm that the SG-targeting construct localizes to insulin granules in β-cells and does not interfere with normal insulin SG behavior. We visualize insulin SG aging behavior in MIN6 and INS1 β-cell lines and in primary C57BL/6J mouse and nondiabetic human islet cells. Finally, we separated young and old insulin SGs, revealing that preferential secretion of younger granules occurs in glucose-stimulated insulin secretion. We also show that SG population age is modulated by the β-cell environment
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