Evidence map›Paper›PMID 31085831›Full record

ArticleJCI insight2019

A glucose-dependent spatial patterning of exocytosis in human β-cells is disrupted in type 2 diabetes.

Jianyang Fu, John Maringa Githaka, Xiaoqing Dai, Gregory Plummer, Kunimasa Suzuki, Aliya F Spigelman, Austin Bautista, Ryekjang Kim, Dafna Greitzer-Antes, Jocelyn E Manning Fox and 2 more

Open access · goldAbstract readVideo-Audio Media
In one paragraph

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.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
3.3field-weighted citation impact, top 8% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

16 citing papers in PubMed, 25 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Review
  5. Review
  6. Spatial organization of lysosomal exocytosis relies on membrane tension gradients.Proceedings of the National Academy of Sciences of the United States of America · 2023
    Article
  7. Insulin secretion hot spots in pancreatic β cells as secreting adhesions.Frontiers in cell and developmental biology · 2023
    Article
  8. Article
  9. Review
  10. Article
  11. Review
  12. Insulin granule biogenesis and exocytosis.Cellular and molecular life sciences : CMLS · 2021
    Review
  13. Review
  14. ZIGIR, a Granule-Specific ZnCell reports · 2020
    Article
  15. Review
  16. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors at 2 institutions in 1 country.

Jianyang FuAlberta Diabetes Institute and Department of Pharmacology and.
John Maringa GithakaDepartment of Biochemistry, University of Alberta, Edmonton, Alberta, Canada.
Xiaoqing DaiAlberta Diabetes Institute and Department of Pharmacology and.
Gregory PlummerAlberta Diabetes Institute and Department of Pharmacology and.
Kunimasa SuzukiAlberta Diabetes Institute and Department of Pharmacology and.
Aliya F SpigelmanAlberta Diabetes Institute and Department of Pharmacology and.
Austin BautistaAlberta Diabetes Institute and Department of Pharmacology and.
Ryekjang KimAlberta Diabetes Institute and Department of Pharmacology and.
Dafna Greitzer-AntesDepartments of Medicine and Physiology, University of Toronto, Toronto, Ontario, Canada.
Jocelyn E Manning FoxAlberta Diabetes Institute and Department of Pharmacology and.
Herbert Y GaisanoDepartments of Medicine and Physiology, University of Toronto, Toronto, Ontario, Canada.
Patrick E MacDonaldAlberta Diabetes Institute and Department of Pharmacology and.
University of Toronto · CAUniversity of Alberta · CA

Funding

CIHR 148451
6 · The paper itself

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.

Indexed as

ExocytosisAdultAgedCells, CulturedDiabetes Mellitus, Type 2FemaleGene Knockdown TechniquesGlucoseHumansInsulinInsulin-Secreting CellsIntravital MicroscopyMaleMicroscopy, FluorescenceMiddle AgedMutagenesis, Site-DirectedGlucoseInsulinKCNB1 protein, humanKcnb1 protein, ratRecombinant ProteinsShab Potassium ChannelsCell BiologyEndocrinologyInsulinIslet cells

Identifiers

PMID31085831
PMCPMC6629118
OpenAlexW2951365338

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.