ArticleJCI insight2019
A glucose-dependent spatial patterning of exocytosis in human β-cells is disrupted in type 2 diabetes.
Article in JCI insight, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 25 citations in OpenAlex.
- Directed insulin secretion from beta cells occurs at cortical sites devoid of microtubules at the edges of ELKS/LL5β patches.Molecular biology of the cell · 2025Article
- Directed insulin secretion from beta cells occurs at cortical sites devoid of microtubules at the edges of ELKS/LL5β patches.bioRxiv : the preprint server for biology · 2025Article
- Comparison of localization and release of multivesicular bodies and secretory granules in islet cells: Dysregulation during type-2 diabetes.Journal of extracellular biology · 2024Article
- Bridging the Gap: Pancreas Tissue Slices From Organ and Tissue Donors for the Study of Diabetes Pathogenesis.Diabetes · 2024Review
- Tissue adaptation to metabolic stress: insights from SUMOylation.Frontiers in endocrinology · 2024Review
- Spatial organization of lysosomal exocytosis relies on membrane tension gradients.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Insulin secretion hot spots in pancreatic β cells as secreting adhesions.Frontiers in cell and developmental biology · 2023Article
- Article
- The changing view of insulin granule mobility: From conveyor belt to signaling hub.Frontiers in endocrinology · 2022Review
- Article
- The Human Islet: Mini-Organ With Mega-Impact.Endocrine reviews · 2021Review
- Insulin granule biogenesis and exocytosis.Cellular and molecular life sciences : CMLS · 2021Review
- Conventional and Unconventional Mechanisms by which Exocytosis Proteins Oversee β-cell Function and Protection.International journal of molecular sciences · 2021Review
- ZIGIR, a Granule-Specific ZnCell reports · 2020Article
- Recent Insights into Beta-cell Exocytosis in Type 2 Diabetes.Journal of molecular biology · 2020Review
- Human Pluripotent Stem Cells: A Unique Tool for Toxicity Testing in Pancreatic Progenitor and Endocrine Cells.Frontiers in endocrinology · 2020Article
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
Impaired insulin secretion in type 2 diabetes (T2D) is linked to reduced insulin granule docking, disorganization of the exocytotic site, and an impaired glucose-dependent facilitation of insulin exocytosis. We show in β-cells from 80 human donors that the glucose-dependent amplification of exocytosis is disrupted in T2D. Spatial analyses of granule fusion, visualized by total internal reflection fluorescence (TIRF) microscopy in 24 of these donors, demonstrate that these are non-random across the surface of β-cells from donors with no diabetes (ND). The compartmentalization of events occurs within regions defined by concurrent or recent membrane-resident secretory granules. This organization, and the number of membrane-associated granules, is glucose-dependent and notably impaired in T2D β-cells. Mechanistically, multi-channel Kv2.1 clusters contribute to maintaining the density of membrane-resident granules and the number of fusion 'hotspots', while SUMOylation sites at the channel N- (K145) and C-terminus (K470) determine the relative proportion of fusion events occurring within these regions. Thus, a glucose-dependent compartmentalization of fusion, regulated in part by a structural role for Kv2.1, is disrupted in β-cells from donors with type 2 diabetes.
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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.