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Hyperinsulinemia impairs functions of circulating endothelial progenitor cells

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Abstract

Aims

Circulating endothelial progenitor cells (EPCs) play a key role in maintaining endothelial function. Dysfunction of EPCs is associated with the cardiovascular complication of diabetes. The purpose of this study is to investigate the direct effects of hyperinsulinemia on EPCs and the underlying mechanisms.

Methods

EPCs isolated from healthy adults were cultured with various concentrations of insulin (control group, without insulin; physiological insulin group, 10 nM insulin and hyperinsulinemia group, 100 nM insulin) with or without phosphatidylinositol-3-kinase (PI3-K) inhibitor (LY294002, 5 µM), endothelial nitric oxide synthase (eNOS) inhibitor (l-NG-nitro-arginine methyl ester (l-NAME), 100 µM), sodium nitroprusside (SNP, 25 µM), p38 mitogen-activated protein kinase(MAPK) inhibitor (SB203580, 5 µM) or extracellular signal-regulated kinases (ERK) 1/2 inhibitor (PD98059, 10 µM). Proliferation, tube formation, and apoptosis of EPCs were determined. Expressions of eNOS, PI3-K, protein kinase B (Akt), p38 MAPK, and ERK 1/2 were assessed.

Results

Hyperinsulinemia caused a significant decrease in proliferation and tube formation abilities than control group. Hyperinsulinemia increased apoptosis rate of EPCs than control group. Furthermore, hyperinsulinemia downregulated phosphorylation of eNOS, PI3-K and Akt, and upregulated phosphorylation of p38 MAPK and ERK. SNP could restore impaired tube formation induced by hyperinsulinemia. P38 MAPK inhibitor but not ERK inhibitor could decrease apoptosis induced by hyperinsulinemia.

Conclusion

Hyperinsulinemia impaired EPCs’ tube formation ability by downregulation of PI-3K/Akt/eNOS pathway. Hyperinsulinemia induced apoptosis of EPCs via upregulation of p38 MAPK.

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Funding

This article was supported by Hebei Province technology supporting projects (16277720D).

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Authors and Affiliations

  1. Department of Cardiology, The First Hospital of Qinhuangdao, Hebei Medical University, Qinhuangdao, Hebei, China

    Qiang Tan, Yang Li, Xuan Li & Shuangyue Zhang

Authors
  1. Qiang Tan
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  2. Yang Li
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  3. Xuan Li
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  4. Shuangyue Zhang
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Correspondence to Qiang Tan.

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All authors declare that they have no conflict of interest.

Ethical approval

This study was appoved by ethical committee of Qinhuangdao First hospital (2016D005).

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All participants provided informed consent prior to their participation.

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Cite this article

Tan, Q., Li, Y., Li, X. et al. Hyperinsulinemia impairs functions of circulating endothelial progenitor cells. Acta Diabetol 56, 785–795 (2019). https://doi.org/10.1007/s00592-019-01314-9

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  • DOI: https://doi.org/10.1007/s00592-019-01314-9

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