Evidence map›Paper›PMID 23423569›Full record

ArticleDiabetes2013

Munc18b is a major mediator of insulin exocytosis in rat pancreatic β-cells.

Patrick P L Lam, Mitsuyo Ohno, Subhankar Dolai, Yu He, Tairan Qin, Tao Liang, Dan Zhu, Youhou Kang, Yunfeng Liu, Maria Kauppi and 8 more

Abstract read
In one paragraph

Article in Diabetes, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.

0numbers the graph read from it
0cells of the map it votes in
31citing papers in PubMed
–field-weighted citation impact
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

31 citing papers in PubMed.

  1. Article
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  3. Article
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  6. Article
  7. The Journal of neuroscience : the official journal of the Society for Neuroscience · 2021
    Article
  8. Review
  9. Review
  10. Review
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Exocytosis proteins as novel targets for diabetes prevention and/or remediation?American journal of physiology. Regulatory, integrative and comparative physiology · 2017
    Review
  17. Article
  18. Article
  19. Article
  20. 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

18 authors.

Patrick P L LamDepartment of Medicine, University of Toronto, Toronto, Ontario, Canada.
Mitsuyo Ohno
Subhankar Dolai
Yu He
Tairan Qin
Tao Liang
Dan Zhu
Youhou Kang
Yunfeng Liu
Maria Kauppi
Li Xie
Wilson C Y Wan
Na-Rhum Bin
Shuzo Sugita
Vesa M Olkkonen
Noriko Takahashi
Haruo Kasai
Herbert Y Gaisano

Funding

Canadian Institutes of Health Research MOP89889
6 · The paper itself

Abstract

Sec1/Munc18 proteins facilitate the formation of trans-SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) complexes that mediate fusion of secretory granule (SG) with plasma membrane (PM). The capacity of pancreatic β-cells to exocytose insulin becomes compromised in diabetes. β-Cells express three Munc18 isoforms of which the role of Munc18b is unknown. We found that Munc18b depletion in rat islets disabled SNARE complex formation formed by syntaxin (Syn)-2 and Syn-3. Two-photon imaging analysis revealed in Munc18b-depleted β-cells a 40% reduction in primary exocytosis (SG-PM fusion) and abrogation of almost all sequential SG-SG fusion, together accounting for a 50% reduction in glucose-stimulated insulin secretion (GSIS). In contrast, gain-of-function expression of Munc18b wild-type and, more so, dominant-positive K314L/R315L mutant promoted the assembly of cognate SNARE complexes, which caused potentiation of biphasic GSIS. We found that this was attributed to a more than threefold enhancement of both primary exocytosis and sequential SG-SG fusion, including long-chain fusion (6-8 SGs) not normally (2-3 SG fusion) observed. Thus, Munc18b-mediated exocytosis may be deployed to increase secretory efficiency of SGs in deeper cytosolic layers of β-cells as well as additional primary exocytosis, which may open new avenues of therapy development for diabetes.

Indexed as

AnimalsExocytosisInsulinInsulin-Secreting CellsInsulin SecretionMaleMunc18 ProteinsQa-SNARE ProteinsRatsRats, Sprague-DawleySecretory VesiclesSyntaxin 1InsulinMunc18 ProteinsQa-SNARE ProteinsSyntaxin 1

Identifiers

PMID23423569
PMCPMC3712044

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Registered trials

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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.