Atorvastatin ameliorates endothelium-specific insulin resistance induced by high glucose combined with high insulin

Yang,Ou; Li,Jinliang; Chen,Haiyan; Li,Jie; Kong,Jian

doi:10.3892/mmr.2016.5564

Atorvastatin ameliorates endothelium-specific insulin resistance induced by high glucose combined with high insulin

Authors:
- Ou Yang
- Jinliang Li
- Haiyan Chen
- Jie Li
- Jian Kong
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Affiliations: Department of Cadre Ward, First Hospital, Jilin University, Changchun, Jilin 130021, P.R. China, Department of Cardiology, Heilongjiang Provincial Hospital, Harbin, Heilongjiang 150001, P.R. China
Published online on: July 27, 2016 https://doi.org/10.3892/mmr.2016.5564
Pages: 2791-2798

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Abstract

The aim of the present study was to establish an endothelial cell model of endothelium-specific insulin resistance to evaluate the effect of atorvastatin on insulin resistance-associated endothelial dysfunction and to identify the potential pathway responsible for its action. Cultured human umbilical vein endothelial cells (HUVECs) were pretreated with different concentrations of glucose with, or without, 10‑5 M insulin for 24 h, following which the cells were treated with atorvastatin. The tyrosine phosphorylation of insulin receptor (IR) and insulin receptor substrate-1 (IRS‑1), the production of nitric oxide (NO), the activity and phosphorylation level of endothelial NO synthase (eNOS) on serine1177, and the mRNA levels of endothelin‑1 (ET‑1) were assessed during the experimental procedure. Treatment of the HUVECs with 30 mM glucose and 10‑5 M insulin for 24 h impaired insulin signaling, with reductions in the tyrosine phosphorylation of IR and protein expression of IRS‑1 by almost 75 and 65%, respectively. This, in turn, decreased the activity and phosphorylation of eNOS on serine1177, and reduced the production of NO by almost 80%. By contrast, the mRNA levels of ET‑1 were upregulated. All these changes were ameliorated by atorvastatin. Taken together, these results demonstrated that high concentrations of glucose and insulin impaired insulin signaling leading to endothelial dysfunction, and that atorvastatin ameliorated these changes, acting primarily through the phosphatidylinositol 3-kinase/Akt/eNOS signaling pathway.

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