The Effect Of Insulin On Sinusoidal Endothelial Cells In Rats With Partial Hepatectomy

Objective Insulin is a hepatocytes growth modilator, which is considered to be essential in liver regeneration and is transported into liver during the process of liver regeneration. However, the stimulation pathways remain unclear. SECs are the second largest number of resident liver cells, and are vital in supplying nutrients and growth factors to proliferating hepatocytes by the formation of new blood vessels during liver regeneration. Vascular endothelial cell growth factor (VEGF) is a potent angiogenic factor that stimulates the proliferation and migration of endothelial cells. The effects of VEGF are known to be mediated through at least two specific receptors, Flt-1 and Flk-1, expressed on the endothelial cell surface. The aim of this study was to determine whether Insulin promotes sinusoidal endothelial cells (SECs) proliferation mediated by up-regulation of vascular endothelial cell growth factor (VEGF) in regenerating rats liver after partial hepatectomy (PHx).Methods Adult male Sprague-Dawley rats undergoing 70% partial hepatectomy were admininstered with insulin (300MU/kg) or saline by injected into the tail veins every 8 hours after surgery for seven days and were sacrificed at 0,24,48, 72, 96, 120,144,168 h postoperatively. Proliferation of both hepatocytes and SECs was monitored by evaluating the proliferation cell nuclear antigen (PCNA) labeling index. The expressions of VEGF protein were evaluated by immunohistochemistry. The mRNA expressions of VEGF and its receptors Flt-1 and Flk-1 were evaluated by semi-quantitative reverse-transcription polymerase chain reaction.Results Insulin markedly increased the expression of VEGF mRNA between 24 h and 120 h after hepatectomy compared with control group. Similarly, insulin significantly increased the expression of Flt-1 between 24 h and 96 h. However insulin had not 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 labeling index of hepatocytes and SECs compared with control group. Conclusions Exogenous insulin may promotes SECs proliferation with an enhancedexpression of VEGF and its receptor Flt-1 in regenerating rats liver after PHx, which suggest that insulin promotes SECs proliferation and subsequently liver regeneration by accelerating the expression of VEGF.