Basic Research
Copyright ©The Author(s) 2005. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Oct 14, 2005; 11(38): 5978-5983
Published online Oct 14, 2005. doi: 10.3748/wjg.v11.i38.5978
Insulin promotes sinusoidal endothelial cell proliferation mediated by upregulation of vascular endothelial growth factor in regenerating rat liver after partial hepatectomy
Jian-Guo Qiao, Long Wu, Dao-Xiong Lei, Lu Wang
Jian-Guo Qiao, Long Wu, Dao-Xiong Lei, Lu Wang, Department of General Surgery, Zhongnan Hospital Affiliated to Wuhan University, Wuhan 430071, Hubei Province, China
Author contributions: All authors contributed equally to the work.
Correspondence to: Jian-Guo Qiao, Department of General Surgery, Zhongnan Hospital Affiliated to Wuhan University, Wuhan 430071, Hubei Province, China. jian_guoqiao@yahoo.com
Telephone: +86-27-67812959 Fax: +86-27-87307622
Received: December 28, 2004
Revised: March 1, 2005
Accepted: March 2, 2005
Published online: October 14, 2005
Abstract

AIM: To determine whether insulin could promote sinusoidal endothelial cell (SEC) proliferation mediated by upregulation of vascular endothelial growth factor (VEGF) in regenerating rat liver after partial hepatectomy (PHx).

METHODS: Adult male Sprague-Dawley rats undergoing 70% PHx were injected with insulin (300 MU/kg) or saline via the tail veins every 8 h after surgery for 7 d and killed at 0, 24, 48, 72, 96, 120, 144, and 168 h after surgery. Proliferation of both hepatocytes and SECs was monitored by evaluating the proliferating cell nuclear antigen (PCNA) labeling index (LI). The expression of VEGF protein was evaluated by immunohistochemistry. The mRNA expressions of VEGF and its receptors Flt-1 and Flk-1 were evaluated by semi-quantitative reverse transcription-PCR.

RESULTS: Insulin markedly increased the expression of VEGF mRNA between 24 and 120 h after hepatectomy compared to controls. Similarly, insulin significantly increased the expression of Flt-1 between 24 and 96 h. However, insulin had no significant effect on Flk-1. Furthermore, the immunohistochemical staining revealed that expression of VEGF protein increased in the insulin groups. Insulin significantly increased the PCNA LI of hepatocytes and SECs compared to controls.

CONCLUSION: Exogenous insulin may promote SEC proliferation with an enhanced expression of VEGF and its receptor Flt-1 inregenerating rat liver after PHx.

Keywords: Insulin; Sinusoidal endothelial cell; VEGF