Evidence map›Paper›PMID 25627423›Full record

ArticleActa physiologica (Oxford, England)2015

Modulation of microRNA-375 expression alters voltage-gated Na(+) channel properties and exocytosis in insulin-secreting cells.

V A Salunkhe, J L S Esguerra, J K Ofori, I G Mollet, M Braun, M Stoffel, A Wendt, L Eliasson

Open access · hybridAbstract read
In one paragraph

Article in Acta physiologica (Oxford, England), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
4.1field-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

22 citing papers in PubMed, 55 citations in OpenAlex.

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  16. MicroRNAs in metabolism.Acta physiologica (Oxford, England) · 2017
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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

8 authors at 3 institutions in 3 countries.

V A SalunkheUnit of Islet Cell Exocytosis, Department of Clinical Sciences in Malmö, Lund University Diabetes Centre, Clinical Research Centre, Lund University, SUS Malmö, Malmö, Sweden.
J L S Esguerra
J K Ofori
I G Mollet
M Braun
M Stoffel
A Wendt
L Eliasson
Lund University · SEETH Zurich · CHUniversity of Alberta · CA

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

aimMiR-375 has been implicated in insulin secretion and exocytosis through incompletely understood mechanisms. Here we aimed to investigate the role of miR-375 in the regulation of voltage-gated Na(+) channel properties and glucose-stimulated insulin secretion in insulin-secreting cells.

methodsMiR-375 was overexpressed using double-stranded mature miR-375 in INS-1 832/13 cells (OE375) or downregulated using locked nucleic acid (LNA)-based anti-miR against miR-375 (LNA375). Insulin secretion was determined using RIA. Exocytosis and ion channel properties were measured using the patch-clamp technique in INS-1 832/13 cells and beta-cells from miR-375KO mice. Gene expression was analysed by RT-qPCR, and protein levels were determined by Western blot.

resultsVoltage-gated Na(+) channels were found to be regulated by miR-375. In INS-1 832/13 cells, steady-state inactivation of the voltage-gated Na(+) channels was shifted by approx. 6 mV to a more negative membrane potential upon down-regulation of miR-375. In the miR-375 KO mouse, voltage-gated Na(+) channel inactivation was instead shifted by approx. 14 mV to a more positive membrane potential. Potential targets differed among species and expression of suggested targets Scn3a and Scn3b in INS-1 832/13 cells was only slightly moderated by miR-375. Modulation of miR-375 levels in INS-1-832/13 cells did not significantly affect insulin release. However, Ca(2+) dependent exocytosis was significantly reduced in OE375 cells.

conclusionWe conclude that voltage-gated Na(+) channels are regulated by miR-375 in insulin-secreting cells, and validate that the exocytotic machinery is controlled by miR-375 also in INS-1 832/13 cells. Altogether we suggest miR-375 to be involved in a complex multifaceted network controlling insulin secretion and its different components.

Indexed as

AnimalsCalciumElectrophysiological PhenomenaGene Expression RegulationGlucoseInsulinIslets of LangerhansMiceMice, KnockoutMicroRNAsRatsReverse Transcriptase Polymerase Chain ReactionVoltage-Gated Sodium ChannelsCalciumGlucoseInsulinMicroRNAsMirn375 microRNA, mouseVoltage-Gated Sodium Channelsexocytosisinsulin secretionmicroRNApatch-clampScn3avoltage-dependent channels

Identifiers

PMID25627423
PMCPMC4413049
OpenAlexW1995459386

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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.