Acta Diabetologica

, Volume 56, Issue 7, pp 785–795 | Cite as

Hyperinsulinemia impairs functions of circulating endothelial progenitor cells

  • Qiang TanEmail author
  • Yang Li
  • Xuan Li
  • Shuangyue Zhang
Original Article



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.


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.


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.


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


Endothelial progenitor cell Diabetes mellitus Insulin Nitric oxide 



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

Compliance with ethical standards

Conflict of interest

All authors declare that they have no conflict of interest.

Ethical approval

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

Informed consent

All participants provided informed consent prior to their participation.

Supplementary material

592_2019_1314_MOESM1_ESM.docx (14 kb)
Supplementary material 1 (DOCX 14 KB)


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Copyright information

© Springer-Verlag Italia S.r.l., part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Cardiology, The First Hospital of QinhuangdaoHebei Medical UniversityQinhuangdaoChina

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