Evidence map›Paper›PMID 30814595›Full record

ArticleScientific reports2019

Insulin secretory granules labelled with phogrin-fluorescent proteins show alterations in size, mobility and responsiveness to glucose stimulation in living β-cells.

Gianmarco Ferri, Luca Digiacomo, Zeno Lavagnino, Margherita Occhipinti, Marco Bugliani, Valentina Cappello, Giulio Caracciolo, Piero Marchetti, David W Piston, Francesco Cardarelli

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
4.4field-weighted citation impact, top 5% 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

24 citing papers in PubMed, 31 citations in OpenAlex.

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  19. ZIGIR, a Granule-Specific ZnCell reports · 2020
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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

10 authors at 6 institutions in 2 countries.

Gianmarco FerriNEST - Scuola Normale Superiore, Istituto Nanoscienze - CNR (CNR-NANO), Pisa, Italy.
Luca DigiacomoDepartment of Molecular Medicine, "La Sapienza" University of Rome, Rome, Italy.
Zeno LavagninoDepartment of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, MO, 63110, USA.
Margherita OcchipintiDepartment of Clinical and Experimental Medicine, Islet Cell Laboratory, University of Pisa, Pisa, Italy.
Marco BuglianiDepartment of Clinical and Experimental Medicine, Islet Cell Laboratory, University of Pisa, Pisa, Italy.ORCID 0000-0002-1744-1561
Valentina CappelloCenter for Nanotechnology Innovation@NEST (CNI@NEST), Pisa, Italy.
Giulio CaraccioloDepartment of Molecular Medicine, "La Sapienza" University of Rome, Rome, Italy.
Piero MarchettiDepartment of Clinical and Experimental Medicine, Islet Cell Laboratory, University of Pisa, Pisa, Italy.
David W PistonDepartment of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, MO, 63110, USA.ORCID 0000-0002-1200-3116
Francesco CardarelliNEST - Scuola Normale Superiore, Istituto Nanoscienze - CNR (CNR-NANO), Pisa, Italy. francesco.cardarelli@sns.it.
University of Pisa · ITSapienza University of Rome · ITWashington University in St. Louis · USCenter for Nanotechnology Innovation · ITIstituto Nanoscienze · ITItalian Institute of Technology · IT

Funding

WU P&FP30DK020579 · NIDDK · WASHINGTON UNIVERSITY · PI Clay F. Semenkovich · 2013 to 2026
$27.1M
Pancreatic Islets Dynamics Regulating Glucagon SecretionR01DK098659 · NIDDK · WASHINGTON UNIVERSITY · PI PISTON, DAVID W · 2013 to 2016
$1.3M
PANCREATIC ISLETS DYNAMICS REGULATING GLUCAGON SECRETIONR56DK098659 · NIDDK · WASHINGTON UNIVERSITY · PI PISTON, DAVID W · 2017 to 2017
$229k
NIDDK NIH HHS R01 DK098659NIDDK NIH HHS R56 DK098659
6 · The paper itself

Abstract

The intracellular life of insulin secretory granules (ISGs) from biogenesis to secretion depends on their structural (e.g. size) and dynamic (e.g. diffusivity, mode of motion) properties. Thus, it would be useful to have rapid and robust measurements of such parameters in living β-cells. To provide such measurements, we have developed a fast spatiotemporal fluctuation spectroscopy. We calculate an imaging-derived Mean Squared Displacement (iMSD), which simultaneously provides the size, average diffusivity, and anomalous coefficient of ISGs, without the need to extract individual trajectories. Clustering of structural and dynamic quantities in a multidimensional parametric space defines the ISGs' properties for different conditions. First, we create a reference using INS-1E cells expressing proinsulin fused to a fluorescent protein (FP) under basal culture conditions and validate our analysis by testing well-established stimuli, such as glucose intake, cytoskeleton disruption, or cholesterol overload. After, we investigate the effect of FP-tagged ISG protein markers on the structural and dynamic properties of the granule. While iMSD analysis produces similar results for most of the lumenal markers, the transmembrane marker phogrin-FP shows a clearly altered result. Phogrin overexpression induces a substantial granule enlargement and higher mobility, together with a partial de-polymerization of the actin cytoskeleton, and reduced cell responsiveness to glucose stimulation. Our data suggest a more careful interpretation of many previous ISG-based reports in living β-cells. The presented data pave the way to high-throughput cell-based screening of ISG structure and dynamics under various physiological and pathological conditions.

Indexed as

AnimalsGlucoseGreen Fluorescent ProteinsInsulin-Secreting CellsInsulin SecretionRatsReceptor-Like Protein Tyrosine Phosphatases, Class 8Secretory VesiclesSweetening Agentsenhanced green fluorescent proteinGlucoseGreen Fluorescent ProteinsPtprn2 protein, ratReceptor-Like Protein Tyrosine Phosphatases, Class 8Sweetening Agents

Identifiers

PMID30814595
PMCPMC6393586
OpenAlexW2920668946

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

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.