Insulin promotes sinusoidal endothelial cell proliferation mediated by upregulation of vascular endothelial growth factor in regenerating rat liver after partial hepatectomy.
OBJECTIVE
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.


CONCLUSIONS
Exogenous insulin may promote SEC proliferation with an enhanced expression of VEGF and its receptor Flt-1 in regenerating rat liver after PHx.
Qiao
Jian-Guo
JG
Department of General Surgery, Zhongnan Hospital Affiliated to Wuhan University, Wuhan 430071, Hubei Province, China. jian_guoqiao@yahoo.com
Wu
Long
L
Lei
Dao-Xiong
DX
Wang
Lu
L
D000818:Animals; D001483:Base Sequence; D049109:Cell Proliferation / Q000187:drug effects; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects; D006498:Hepatectomy; D007328:Insulin / Q000494:pharmacology*; D008099:Liver / Q000098:blood supply / Q000187:drug effects / Q000502:physiology*; D008115:Liver Regeneration; D008297:Male; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015854:Up-Regulation / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000235:genetics; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics
D007328:Insulin; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; C501164:Flt1 protein, rat; D040281:Vascular Endothelial Growth Factor Receptor-1; D040301:Vascular Endothelial Growth Factor Receptor-2