Evidence map›Paper›PMID 28173719›Full record

ArticleAntioxidants & redox signaling2017

Exosomal MicroRNA-15a Transfer from the Pancreas Augments Diabetic Complications by Inducing Oxidative Stress.

Tengku Ain Kamalden, Anne M Macgregor-Das, Sangeetha Marimuthu Kannan, Brittany Dunkerly-Eyring, Nurliza Khaliddin, Zhenhua Xu, Anthony P Fusco, Syatirah Abu Yazib, Rhuen Chiou Chow, Elia J Duh and 3 more

Open access · greenAbstract read
In one paragraph

Article in Antioxidants & redox signaling, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 83 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
83citing papers in PubMed, 1 pooled it
5.4field-weighted citation impact, top 3% 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

83 citing papers in PubMed, 1 synthesis or guideline pooled it, 138 citations in OpenAlex.

  1. Epigenetic Mechanisms in Type 2 Diabetes Retinopathy: A Systematic Review.International journal of molecular sciences · 2021
    Pooled it
  2. Review
  3. Article
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  5. Article
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  7. Article
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  9. Review
  10. Islet Tissue Macrophages in Immunity Homeostasis and Type 1 Diabetes.Clinical reviews in allergy & immunology · 2025
    Review
  11. Article
  12. Emerging role of exosomal-microRNA in obesity.Current opinion in physiology · 2025
    Article
  13. Article
  14. Article
  15. Article
  16. Advances in Nanomedicine for Precision Insulin Delivery.Pharmaceuticals (Basel, Switzerland) · 2024
    Review
  17. Review
  18. Review
  19. Review
  20. Review

23 more citing papers are in PubMed but not listed here.

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

13 authors at 3 institutions in 3 countries.

Tengku Ain Kamalden1 University of Malaya Eye Research Centre, Department of Ophthalmology, University of Malaya , Kuala Lumpur, Malaysia .
Anne M Macgregor-Das2 Department of Pathology, Johns Hopkins University , Baltimore, Maryland.
Sangeetha Marimuthu Kannan2 Department of Pathology, Johns Hopkins University , Baltimore, Maryland.
Brittany Dunkerly-Eyring2 Department of Pathology, Johns Hopkins University , Baltimore, Maryland.
Nurliza Khaliddin1 University of Malaya Eye Research Centre, Department of Ophthalmology, University of Malaya , Kuala Lumpur, Malaysia .
Zhenhua Xu4 Department of Ophthalmology, Johns Hopkins University , Baltimore, Maryland.
Anthony P Fusco5 Firefly, An Abcam Company , Cambridge, Massachusetts.
Syatirah Abu Yazib1 University of Malaya Eye Research Centre, Department of Ophthalmology, University of Malaya , Kuala Lumpur, Malaysia .
Rhuen Chiou Chow1 University of Malaya Eye Research Centre, Department of Ophthalmology, University of Malaya , Kuala Lumpur, Malaysia .
Elia J Duh4 Department of Ophthalmology, Johns Hopkins University , Baltimore, Maryland.
Marc K Halushka2 Department of Pathology, Johns Hopkins University , Baltimore, Maryland.
Charles Steenbergen2 Department of Pathology, Johns Hopkins University , Baltimore, Maryland.
Samarjit Das2 Department of Pathology, Johns Hopkins University , Baltimore, Maryland.
Johns Hopkins University · USUniversity Malaya Medical Centre · MYAbcam (United States) · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

aimsMicroRNAs (miRNAs), one type of noncoding RNA, modulate post-transcriptional gene expression in various pathogenic pathways in type 2 diabetes (T2D). Currently, little is known about how miRNAs influence disease pathogenesis by targeting cells at a distance. The purpose of this study was to investigate the role of exosomal miRNAs during T2D.

resultsWe show that miR-15a is increased in the plasma of diabetic patients, correlating with disease severity. miR-15 plays an important role in insulin production in pancreatic β-cells. By culturing rat pancreatic β-cells (INS-1) cells in high-glucose media, we identified a source of increased miR-15a in the blood as exosomes secreted by pancreatic β-cells. We postulate that miR-15a, produced in pancreatic β-cells, can enter the bloodstream and contribute to retinal injury. miR-15a overexpression in Müller cells can be induced by exposing Müller cells to exosomes derived from INS-1 cells under high-glucose conditions and results in oxidative stress by targeting Akt3, which leads to apoptotic cell death. The in vivo relevance of these findings is supported by results from high-fat diet and pancreatic β-cell-specific miR-15a INNOVATION: This study highlights an important and underappreciated mechanism of remote cell-cell communication (exosomal transfer of miRNA) and its influence on the development of T2D complications.

conclusionOur findings suggest that circulating miR-15a contributes to the pathogenesis of diabetes and supports the concept that miRNAs released by one cell type can travel through the circulation and play a role in disease progression via their transfer to different cell types, inducing oxidative stress and cell injury. Antioxid. Redox Signal. 27, 913-930.

Indexed as

AdultAnimalsCell LineDiabetes Mellitus, Type 2Diabetic RetinopathyDisease Models, AnimalExosomesFemaleHumansInsulin-Secreting CellsMaleMiceMicroRNAsMiddle AgedOxidative StressRatsMicroRNAsMIRN15 microRNA, humandiabetic vasculopathyexosomesmicroRNAoxidative stresspancreatic β-cells

Identifiers

PMID28173719
PMCPMC5649125
OpenAlexW2586708379

What OpenQuestion holds

Textmetadata
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 OpenQuestion graph.