This investigation used primary cultured rat vascular smooth muscle cells (VSMCs) to examine the effects of insulin (INS) on proliferation of VSMCs. In this study, protein kinase B (Akt) and p42/44 mitogen-activated protein kinase (ERK 1/2) signaling pathways in mediating the mitogenic actions of INS in VSMCs was investigated. Incubation of a rat VSMCs with INS (100 nM) for 10 min resulted in an increase of Akt phosphorylation by 6-fold (P<0.001) and ERK 1/2 phosphorylation by 3-fold (P<0.001). Pretreatment for 15 min with 10 μM of P13 K/Akt inhibitor LY294002 or with 20 μM inhibitor of ERK 1/2 PD98059 significantly reduced INS-stimulated Akt and ERK 1/2 phosphorylation by 76% and by 75%, respectively. Incubation of a rat VSMCs with INS resulted in an increase of VSMC proliferation (CONT=100%, INS=187±13%, P<0.001.) The effect of INS on VSMC proliferation was significantly reduced by 68% by pretreatment with LY294002 (P>0.01) and by 71% (P>0.01) by pretreatment with PD98059. These results indicate that INS acts through Akt and ERK 1/2 signaling pathways to up-regulate proliferation of VSMCs.
03 - 07 May 2008
European Society of Endocrinology