Insulin enhances neointimal hyperplasia following arterial injury through the PI3K/Akt pathway in type 1 diabetic rats

Cai,Jin; Wang,Huaiming; Sang,Hongfei; Ye,Ruidong; Cao,Yuezhou; Jing,Mei; Liu,Keting; Xie,Yi; Qiu,Zhongming; Guo,Ruibing; Lv,Qiushi; Liu,Xinfeng

doi:10.3892/mmr.2020.11628

Insulin enhances neointimal hyperplasia following arterial injury through the PI3K/Akt pathway in type 1 diabetic rats

Authors:
- Jin Cai
- Huaiming Wang
- Hongfei Sang
- Ruidong Ye
- Yuezhou Cao
- Mei Jing
- Keting Liu
- Yi Xie
- Zhongming Qiu
- Ruibing Guo
- Qiushi Lv
- Xinfeng Liu
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Affiliations: Department of Neurology, Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu 210002, P.R. China, Department of Geriatrics, The 455th Hospital of Chinese People's Liberation Army, Shanghai 200052, P.R. China
Published online on: October 22, 2020 https://doi.org/10.3892/mmr.2020.11628
Pages: 5472-5478

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Abstract

Although insulin is known to affect neointimal hyperplasia via distinct signaling pathways, how neointimal hyperplasia is affected in insulin‑deficient type 1 diabetes remains unknown. The aim of the current study was to investigate two major signaling branches of insulin action regulating neointimal hyperplasia following arterial injury in type 1 diabetes with or without exogenous insulin administration. Rats were treated with vehicle (control group), streptozotocin (STZ) alone (STZ group; uncontrolled type 1 diabetes) or STZ followed by insulin (STZ + I group; controlled type 1 diabetes). Subsequently, a type 1 diabetic rat model of carotid artery balloon injury was established. Following this, the intima‑to‑media area ratios were examined for evidence of neointimal hyperplasia in the carotid arteries of the rats by performing hematoxylin‑eosin staining. Furthermore, the protein expression of extracellular signal‑regulated kinase (ERK), phosphorylated (p‑) ERK, protein kinase B (Akt) and p‑Akt in the carotid arteries of the rats was determined via immunoblotting. Moreover, an in vitro model of type 1 diabetes was induced by incubation of primary vascular smooth muscle cells (VSMCs) with glucose and/or insulin. Cellular proliferation and signaling protein expression levels in VSMCs were determined by measuring the incorporation of tritiated thymidine and performing immunoblotting, respectively. The results demonstrated that compared with that in control rats, neointimal hyperplasia and expression of p‑Akt in uncontrolled type 1 diabetic rats were significantly decreased. This decrease was recovered in controlled type 1 diabetes with insulin therapy. Furthermore, the difference in the expression of p‑ERK between groups was not significant. Additionally, the results of the cell experiments were consistent with those from the animal studies. In conclusion, the preferential signaling along the phosphatidylinositol 3‑kinase/Akt pathway of insulin action in response to insulin restoration may contribute to neointimal hyperplasia. The present study provides a novel approach for the further treatment of neointimal hyperplasia in type 1 diabetes.

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