Evidence map›Paper›PMID 34117507›Full record

ArticleDiabetologia2021

M1 macrophage-derived exosomes impair beta cell insulin secretion via miR-212-5p by targeting SIRT2 and inhibiting Akt/GSK-3β/β-catenin pathway in mice.

Bin Qian, Yang Yang, Ningyuan Tang, Jiahui Wang, Peng Sun, Nan Yang, Fang Chen, Tijun Wu, Tong Sun, Yating Li and 4 more

Open access · bronzeAbstract read
PubMed Publisher
In one paragraph

Article in Diabetologia, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers.

0numbers the graph read from it
0cells of the map it votes in
67citing papers in PubMed
5.1field-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

67 citing papers in PubMed, 87 citations in OpenAlex.

  1. Article
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  6. Article
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  8. Article
  9. Glucolipid Metabolic Disorders andInternational journal of endocrinology · 2026
    Review
  10. Review
  11. Review
  12. Islet Tissue Macrophages in Immunity Homeostasis and Type 1 Diabetes.Clinical reviews in allergy & immunology · 2025
    Review
  13. Review
  14. Article
  15. Review
  16. Article
  17. Review
  18. Article
  19. Review
  20. Review

7 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

14 authors at 2 institutions in 1 country.

Bin QianKey Laboratory of Human Functional Genomics of Jiangsu Province, Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, China.
Yang YangKey Laboratory of Human Functional Genomics of Jiangsu Province, Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, China.
Ningyuan TangKey Laboratory of Human Functional Genomics of Jiangsu Province, Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, China.
Jiahui WangKey Laboratory of Human Functional Genomics of Jiangsu Province, Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, China.
Peng SunKey Laboratory of Human Functional Genomics of Jiangsu Province, Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, China.
Nan YangKey Laboratory of Human Functional Genomics of Jiangsu Province, Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, China.
Fang ChenKey Laboratory of Human Functional Genomics of Jiangsu Province, Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, China.
Tijun WuKey Laboratory of Human Functional Genomics of Jiangsu Province, Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, China.
Tong SunKey Laboratory of Human Functional Genomics of Jiangsu Province, Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, China.
Yating LiKey Laboratory of Human Functional Genomics of Jiangsu Province, Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, China.
Xiaoai ChangKey Laboratory of Human Functional Genomics of Jiangsu Province, Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, China.
Yunxia ZhuKey Laboratory of Human Functional Genomics of Jiangsu Province, Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, China.
Yaqin ZhangKey Laboratory of Human Functional Genomics of Jiangsu Province, Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, China. yaqinzhang@njmu.edu.cn.ORCID 0000-0003-3436-4569
Xiao HanKey Laboratory of Human Functional Genomics of Jiangsu Province, Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, China. hanxiao@njmu.edu.cn.ORCID 0000-0002-6467-1802
Nanjing Medical University · CNChina Pharmaceutical University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

aims/hypothesisMacrophage levels are elevated in pancreatic islets, and the resulting inflammatory response is a major contributor to beta cell failure during obesity and type 2 diabetes mellitus. Previous studies by us and others have reported that exosomes released by macrophages play important roles in mediating cell-to-cell communication, and represent a class of inflammatory factors involved in the inflammatory process associated with type 2 diabetes mellitus. However, to date, no reports have demonstrated the effect of macrophage-derived exosomes on beta cells, and little is known regarding their underlying mechanisms in beta cell injury. Thus, we aimed to study the impact of macrophage-derived exosomes on islet beta cell injury in vitro and in vivo.

methodsThe phenotypic profiles of islet-resident macrophages were analysed in C57BL/6J mice fed a high-fat diet (HFD). Exosomes were collected from the medium of cultured bone marrow-derived macrophages (BMDMs) and from isolated islet-resident macrophages of HFD-fed mice (HFD-Exos). The role of exosomes secreted by inflammatory M1 phenotype BMDMs (M1-Exos) and HFD-Exos on beta cell function was assessed. An miRNA microarray and quantitative real-time PCR (qPCR) were conducted to test the level of M1-Exos-derived miR-212-5p in beta cells. Then, miR-212-5p was overexpressed or inhibited in M1-Exos or beta cells to determine its molecular and functional impact.

resultsM1-polarised macrophages were enriched in the islets of obese mice. M1 macrophages and islet-resident macrophages of HFD-fed mice impaired beta cell insulin secretion in an exosome-dependent manner. miR-212-5p was notably upregulated in M1-Exos and HFD-Exos. Enhancing the expression of miR-212-5p impaired beta cell insulin secretion. Blocking miR-212-5p elicited a significant improvement in M1-Exos-mediated beta cell insulin secretion during injury. Mechanistically, M1-Exos mediated an intercellular transfer of the miR-212-5p, targeting the sirtuin 2 gene and regulating the Akt/GSK-3β/β-catenin pathway in recipient beta cells to restrict insulin secretion. CONCLUSIONS/

interpretationA novel exosome-modulated mechanism was delineated for macrophage-beta cell crosstalk that drove beta cell dysfunction and should be explored for its therapeutic utility.

Indexed as

Diabetes Mellitus, Type 2ExosomesMicroRNAsAnimalsbeta CateninGlycogen Synthase Kinase 3 betaInsulin SecretionMacrophagesMiceMice, Inbred C57BLProto-Oncogene Proteins c-aktSirtuin 2beta CateninGlycogen Synthase Kinase 3 betaMicroRNAsProto-Oncogene Proteins c-aktSirt2 protein, mouseSirtuin 2Beta cellExosomeIslet inflammationMacrophagemiR-212-5p

Identifiers

PMID34117507
OpenAlexW3171949034

What OpenQuestion holds

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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.