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Journal of Traditional Chinese Medicine >

2025 , Vol. 45 >Issue 6: 1228 - 1237

DOI: https://doi.org/10.19852/j.cnki.jtcm.2025.06.005

Original Articles

Electroacupuncture alleviates type 2 diabetes mellitus by promoting plasma-derived exosomal circular RNA of enhancer of zeste homolog 1 expression

  • Yin SHOU ,
  • Juntao JIANG ,
  • Jianlin HU ,
  • Wei JI ,
  • Chunyan CHEN ,
  • Li HU ,
  • Yuhang MA ,
  • Bimeng ZHANG
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  • 1 Department of Acupuncture-Moxibustion, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200000, China
    2 Department of Urology, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200000, China
    3 Department of Reproduction, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200000, China
    4 Department of Traditional Chinese Orthopedics, Xiangshan TCM Hospital, Shanghai, China
    5 Shanghai Research Institute of Qigong, Taiji Health Center, Shanghai University of Traditional Chinese Medicine, Shanghai 200000, China
    6 Acumox and Tuina Research Section, College of Acumox and Tuina, Shanghai University of Traditional Chinese Medicine, Shanghai 200000, China
    7 Department of Endorcinolgy and Metabolism, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200000, China
SHOU Yin and HU Jianlin are co-first authors and contributed equally to this work

Received date: 2024-11-12

  Accepted date: 2025-05-07

  Online published: 2025-11-24

Supported by

Science and Technology Committee of Songjiang District, Shanghai(2024SJKJGG001);project: Mechanistic Study on the Therapeutic Effect of Electroacupuncture in Diabetic Osteoporosis via Exosomal circular RNA of Enhancer of Zeste Homolog 1-Regulated miR-128/ Transient Receptor Potential Vanilloid 1 Axis-Mediated Ferroptosis in Osteoclasts; the Shanghai Municipal Health Bureau [grant number: 2020LP010];Project: a Randomized Controlled Study of Traditional Chinese Acupuncture Combined with Rehabilitation Training for the Treatment of Intensive Care Unit-Acquired Weakness; the Science and Technology Commission of Shanghai Municipality (grant number: 20511101204);Project: Traditional Chinese Medicine Data Collection and Governance for Early Screening and Stratified Diagnosis and Treatment of Pancreatic Cancer; the Shanghai University of Traditional Chinese Medicine (grant number: 2021LK100);Project: the Role of Sestrin 2/mechanistic Target of Rapamycin-Mediated Autophagy in Age-Related Skeletal Muscle Atrophy and the Effects of Acupuncture;Shanghai General Hospital(grant number: 202220);Project: Research on the Construction of Talent Evaluation System by the Southern Outpatient Party Branch; and Shanghai Municipal Commission of Health and Family Planning [grant number: ZY(2021-2023)-0208];Project: Special Program of the Integrated Chinese and Western Medicine Innovation Research Institute

Fold

Abstract

OBJECTIVE: To investigate the effect of electroacupuncture (EA) on regulatory functions of one specific exosomal circRNA of Enhancer of Zeste Homolog (CircEZH) and its potential mechanisms of action in type 2 diabetes (T2DM).

METHODS: Mice were fed a high-fat diet (HFD) and intraperitoneally injected with streptozotocin to create the T2DM model and then were used for two experiments involving the following groups: experiment 1 (control group, T2DM group, T2DM+EA group, 10 mice per group) and experiment 2 [control group, T2DM group, T2DM+ CircEZH1-siRNA (20 nmol/20 g) group, 10 mice per group]. Exosomal size, distribution, and morphology were evaluated via transmission electron microscopy and nanoparticle tracking analysis. The expression of CircEZH1 and CircEZH2 in exosomes was assessed by quantitative real-time polymerase chain reaction. Insulin expression was assessed by enzyme-linked immunosorbent assay, immunofluorescence, and western blotting. The effects of exosomal CircEZH1 knockout and overexpression in Min6 cells were assessed by cell counting kit-8 and flow cytometry. Meanwhile, the effect of CircEZH1 knockout on insulin sensitivity was assessed by glucose tolerance test (GTT) and insulin tolerance test (ITT) in vivo.

RESULTS: EA treatment significantly reduced the serum insulin level and cell apoptosis in pancreatic tissue in a T2DM model. EA treatment markedly upregulated CircEZH1 expression in the exosomes of T2DM mice. Further study showed that CircEZH1 overexpression resulted in increased Min6 cell viability and decreased Min6 cell apoptosis when compared with the levels in an overexpression control group. In Min6 cells with CircEZH1 knockout, the opposite trends were identified. CircEZH1-knockout Min6 cells also showed reduced insulin expression. In vivo, CircEZH1-knockout T2DM mice displayed damaged insulin sensitivity, which was demonstrated by elevated levels of fasting blood glucose and decreased glucose tolerance in the GTT and insulin sensitivity in the ITT.

CONCLUSIONS: EA can affect CircEZH1 expression specifically in the exosomes in β cells in the pancreatic islets to improve T2DM. Exosomal CircEZH1 is a potential therapeutic candidate to treat T2DM.

Key words： diabetes mellitus, type 2; electroacupuncture; diet, high-fat; exosomal CircEZH1

Cite this article

Yin SHOU , Juntao JIANG , Jianlin HU , Wei JI , Chunyan CHEN , Li HU , Yuhang MA , Bimeng ZHANG . Electroacupuncture alleviates type 2 diabetes mellitus by promoting plasma-derived exosomal circular RNA of enhancer of zeste homolog 1 expression[J]. Journal of Traditional Chinese Medicine, 2025 , 45(6) : 1228 -1237 . DOI: 10.19852/j.cnki.jtcm.2025.06.005

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