Evidence map›Paper›PMID 25973389›Full record

ArticleMolecular metabolism2015

Munc18c mediates exocytosis of pre-docked and newcomer insulin granules underlying biphasic glucose stimulated insulin secretion in human pancreatic beta-cells.

Dan Zhu, Li Xie, Negar Karimian, Tao Liang, Youhou Kang, Ya-Chi Huang, Herbert Y Gaisano

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular metabolism, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
3.8field-weighted citation impact, top 7% 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

14 citing papers in PubMed, 25 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Insulin granule biogenesis and exocytosis.Cellular and molecular life sciences : CMLS · 2021
    Review
  5. Review
  6. Article
  7. Review
  8. Article
  9. The cell biology of systemic insulin function.The Journal of cell biology · 2018
    Review
  10. Article
  11. Article
  12. Article
  13. Article
  14. 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

7 authors at 1 institution in 1 country.

Dan ZhuDepartment of Medicine, Faculty of Medicine, University of Toronto, Toronto, ON, Canada.
Li XieDepartment of Medicine, Faculty of Medicine, University of Toronto, Toronto, ON, Canada.
Negar KarimianDepartment of Medicine, Faculty of Medicine, University of Toronto, Toronto, ON, Canada.
Tao LiangDepartment of Medicine, Faculty of Medicine, University of Toronto, Toronto, ON, Canada.
Youhou KangDepartment of Medicine, Faculty of Medicine, University of Toronto, Toronto, ON, Canada.
Ya-Chi HuangDepartment of Medicine, Faculty of Medicine, University of Toronto, Toronto, ON, Canada.
Herbert Y GaisanoDepartment of Medicine, Faculty of Medicine, University of Toronto, Toronto, ON, Canada.
University of Toronto · CA

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

objectivePancreatic beta-cells express three Munc18 isoforms. Much is known about the roles of Munc18a (pre-docked secretory granules-SGs) and Munc18b (newcomer SGs and SG-SG fusion) in insulin exocytosis. Although shown to influence glucose-stimulated insulin secretion (GSIS) in rodents the precise role of Munc18c in insulin SG exocytosis has not been elucidated. We here examined the role of Munc18c in human pancreatic beta-cells.

methodsMunc18c-shRNA/RFP lenti-virus (versus control virus) was used to knock down the expression level of Munc18c in human islets or single beta-cells. Insulin secretion and granule exocytosis were measured by performing islets perifusion, single-cell patch clamp capacitance measurements and total internal reflection fluorescence microscopy (TIRFM).

resultsMunc18c is most abundant in the cytosol of human beta-cells. Endogenous function of Munc18c was assessed by knocking down (KD) its islet expression by 70% employing lenti-shRNA virus. Munc18c-KD caused reduction in cognate syntaxin-4 islet expression but not in other exocytotic proteins, resulting in the reduction in GSIS in first- (by 42%) and second phases (by 35%). Single cell analyses of RFP-tagged Munc18c-KD beta-cells by patch clamp capacitance measurements showed inhibition in both readily-releasable pool (by 52%) and mobilization from the reserve pool (by 57%). TIRFM to assess single SG behavior showed that Munc18c-KD inhibition of first phase GSIS was attributed to reduction in exocytosis of pre-docked and newcomer SGs, and second phase inhibition attributed entirely to reduction in newcomer SG fusion (SGs that undergo minimal residence or docking time at the plasma membrane before fusion).

conclusionMunc18c is involved in the distinct molecular machineries that affect exocytosis of both predocked and newcomer SG pools that underlie Munc18c's role in first and second phases of GSIS, respectively.

Indexed as

Ad, adenovirusCmPatch, clamp capacitance measurementsEGFP, enhanced green fluorescent proteinExocytosisGLP-1, glucagon-like peptide-1GSIS, glucose-stimulated insulin secretionHuman isletsKD, knock downMunc18cNewcomer insulin granulesNPY, neuropeptide YPM, plasma membraneRRP, readily releasable poolSG, secretory insulin-containing granuleSM, Sec1/Munc18-like proteinSNAP25/23, synaptosomal-associated protein of 25/23 kDSNARE, soluble N-ethylmaleimide-sensitive factor attachment protein receptorSyn, syntaxinT2DM, type 2 diabetes mellitusTIRFM, total internal reflection fluorescence microscopyt-, target-VAMPs, Vesicle Associated Membrane Proteinsv-, vesicle-

Identifiers

PMID25973389
PMCPMC4421095
OpenAlexW2075001023

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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 Socratic graph.