Evidence map›Paper›PMID 40102237›Full record

ArticleDiabetologia2025

Comprehensive sequencing profile and functional analysis of IsomiRs in human pancreatic islets and beta cells.

Stefano Auddino, Elena Aiello, Giuseppina E Grieco, Daniela Fignani, Giada Licata, Marco Bruttini, Alessia Mori, Andrea F Berteramo, Erika Pedace, Laura Nigi and 14 more

Abstract read
In one paragraph

Article in Diabetologia, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Review
  2. Review
  3. 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

24 authors.

Stefano AuddinoDiabetes Unit, Department of Medicine, Surgery and Neurosciences, University of Siena, Siena, Italy.ORCID http://orcid.org/0000-0002-7919-5597
Elena AielloDiabetes Unit, Department of Medicine, Surgery and Neurosciences, University of Siena, Siena, Italy.ORCID http://orcid.org/0000-0002-2054-4369
Giuseppina E GriecoDiabetes Unit, Department of Medicine, Surgery and Neurosciences, University of Siena, Siena, Italy.ORCID http://orcid.org/0000-0001-7325-6128
Daniela FignaniDiabetes Unit, Department of Medicine, Surgery and Neurosciences, University of Siena, Siena, Italy.ORCID http://orcid.org/0000-0001-8803-5846
Giada LicataDiabetes Unit, Department of Medicine, Surgery and Neurosciences, University of Siena, Siena, Italy.ORCID http://orcid.org/0000-0001-6995-8581
Marco BruttiniTuscany Centre for Precision Medicine (CReMeP), Siena, Italy.ORCID http://orcid.org/0000-0003-1063-2522
Alessia MoriTuscany Centre for Precision Medicine (CReMeP), Siena, Italy.ORCID http://orcid.org/0009-0002-3344-2772
Andrea F BerteramoDiabetes Unit, Department of Medicine, Surgery and Neurosciences, University of Siena, Siena, Italy.ORCID http://orcid.org/0009-0002-5663-6414
Erika PedaceDiabetes Unit, Department of Medicine, Surgery and Neurosciences, University of Siena, Siena, Italy.ORCID http://orcid.org/0000-0002-0131-8534
Laura NigiDiabetes Unit, Department of Medicine, Surgery and Neurosciences, University of Siena, Siena, Italy.ORCID http://orcid.org/0000-0002-6251-3069
Caterina FormichiDiabetes Unit, Department of Medicine, Surgery and Neurosciences, University of Siena, Siena, Italy.ORCID http://orcid.org/0000-0001-7703-8216
Claudiane GuayDepartment of Fundamental Neurosciences, University of Lausanne, Lausanne, Switzerland.ORCID http://orcid.org/0000-0002-6478-8744
Giuseppe QueroDipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Rome, Italy.ORCID http://orcid.org/0000-0002-0001-9479
Vincenzo TondoloGeneral Surgery Unit, Fatebenefratelli Isola Tiberina-Gemelli Isola, Rome, Italy.ORCID http://orcid.org/0000-0003-0256-3766
Gianfranco Di GiuseppeDipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Rome, Italy.ORCID http://orcid.org/0000-0003-4506-5193
Laura SoldovieriDipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Rome, Italy.ORCID http://orcid.org/0009-0001-3315-0406
Gea CiccarelliDipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Rome, Italy.ORCID http://orcid.org/0009-0001-3621-6298
Andrea MariInstitute of Neuroscience, National Research Council, Padua, Italy.ORCID http://orcid.org/0000-0002-1436-5591
Andrea GiaccariDipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Rome, Italy.ORCID http://orcid.org/0000-0002-7462-7792
Teresa MezzaDipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Rome, Italy.ORCID http://orcid.org/0000-0001-5407-9576
Agnese PoDepartment of Molecular Medicine, Sapienza University of Rome, Rome, Italy.ORCID http://orcid.org/0000-0002-9346-8782
Romano RegazziDepartment of Fundamental Neurosciences, University of Lausanne, Lausanne, Switzerland.ORCID http://orcid.org/0000-0002-9773-2915
Francesco DottaDiabetes Unit, Department of Medicine, Surgery and Neurosciences, University of Siena, Siena, Italy. francesco.dotta@unisi.it.ORCID http://orcid.org/0000-0003-4947-7478
Guido SebastianiDiabetes Unit, Department of Medicine, Surgery and Neurosciences, University of Siena, Siena, Italy.ORCID http://orcid.org/0000-0003-4374-8564

Funding

Bando Ricerca Finalizzata 2018, Italian Ministry of Health GR-2018-12365577F-CUR, University of Siena 2268-2022-SG-PSR2021-FCUR_001Innovative Medicines Initiative 2 (IMI2) Joint Undertaking 115797 INNODIAInnovative Medicines Initiative 2 (IMI2) Joint Undertaking 945268 INNODIA HARVESTItalian Ministry of University and Research 2017KAM2R5_003Italian Ministry of University and Research (MUR) PNRR "National Center for Gene Therapy and Drugs based on RNA Technology" , CN3 Spoke #5 "Inflammatory and Infectious Diseases" Project No. CN00000041
6 · The paper itself

Abstract

aims/hypothesisMiRNAs regulate gene expression, influencing beta cell function and pathways. Isoforms of miRNA (isomiRs), sequence variants of miRNAs with post-transcriptional modifications, exhibit cell-type-specific expression and functions. Despite their biological significance, a comprehensive isomiR profile in human pancreatic islets and beta cells remains unexplored. This study aims to profile isomiR expression in four beta cell sources: (1) laser capture microdissected human islets (LCM-HI); (2) collagenase-isolated human islets (CI-HI); (3) sorted beta cells; and (4) the EndoC-βH1 beta cell line, and to investigate their potential role in beta cell function.

methodsSmall RNA-seq and/or small RNA dataset analysis was conducted on human pancreatic islets and beta cells. Data were processed using the sRNAbench bioinformatics pipeline to classify isomiRs based on sequence variations. A beta cell-specific isomiR signature was identified via cross-validation across datasets. Correlations between LCM-HI isomiR expression and in vivo clinical parameters were analysed using regression models. Functional validation of isomiR-411-5p-Ext5p(+1) was performed via overexpression in EndoC-βH1 cells and CI-HI, followed by glucose-stimulated insulin secretion (GSIS) assays and/or transcriptomic analysis.

resultsIsomiRs constituted 59.2 ± 1.9% (LCM-HI), 59.6 ± 2.4% (CI-HI), 42.3 ± 7.2% (sorted beta cells) and 43.8 ± 1.2% (EndoC-βH1) of total miRNA reads (data represented as mean ± SD), with 3' end trimming (Trim3p) being the predominant modification. A beta cell-specific isomiR signature of 30 sequences was identified, with isomiR-411-5p-Ext5p(+1) showing a significant inverse correlation with basal insulin secretion (p=0.0009, partial R CONCLUSIONS/

interpretationThis study provides the first comprehensive isomiR profiling in human islets and beta cells, revealing their substantial contribution to miRNA regulation. IsomiR-411-5p-Ext5p(+1) emerges as a distinct key modulator of insulin secretion and granule dynamics in beta cells. These findings highlight isomiRs as potential biomarkers and therapeutic targets for diabetes, warranting further exploration of their roles in beta cell biology.

Indexed as

Insulin-Secreting CellsIslets of LangerhansMicroRNAsAdultCell LineFemaleHumansInsulinInsulin SecretionMaleMiddle AgedInsulinMicroRNAsBeta cellBeta cell functionHuman pancreatic isletsInsulin secretionIsomiRsMicroRNAsNon-coding RNAs

Identifiers

PMID40102237
PMCPMC12069488

What Socratic holds

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LicenceCC BY
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