Ghrelin exhibits its biological effect through binding to the growth hormone 
secretagogue 1a receptor (GHS-R1a). Recently, it has been reported that ghrelin 
has an anti-apoptotic effect in several cell types. However, the molecule 
mechanisms underlying the anti-apoptotic effect of ghrelin remain poorly 
understood. In this study, we investigated the intracellular mechanisms 
responsible for anti-apoptotic effect of ghrelin on human umbilical vein 
endothelial cells (HUVEC). Treatment of HUVEC with ghrelin inhibited high 
glucose-induced cell apoptosis. Ghrelin stimulated the rapid phosphorylation of 
mammalian target of rapamycin (mTOR), P70S6K and S6. The GHS-R1a-specific 
antagonist [D-Lys3]-GHRP-6 abolished the anti-apoptotic effect and inhibited the 
activation of mTOR, P70S6K, S6 induced by ghrelin. Pretreatment of cells with 
specific inhibitor of mTOR blocked the anti-apoptotic effect of ghrelin. In 
addition, ghrelin protected HUVECs against high glucose induced apoptosis by 
increasing Bcl-2/Bax ratio. Taken together, our results demonstrate that ghrelin 
produces a protective effect on HUVECs through activating GHS-R1a and 
mTOR/P70S6K signaling pathway mediates the effect of ghrelin. These observations 
suggest that ghrelin may act as a survival factor in preventing HUVECs apoptosis 
caused by high glucose.