Endocrine Abstracts (2008) 16 P652

Insulin regulation of proliferation involves activation of akt and erk 1/2 signaling pathways in vascular smooth muscle cells

Esma Isenovic1, Maxenence Fretaud2, Goran Koricanac1, Emina Sudar1, Jelena Velebit1, Branislava Dobutovic1 & Pierre Marche2

1Institute Vinca, Belgrade, Serbia, USA; 22CNRS UMR 7131, and University Pierre and Marie Curie, Hôpital Broussais, Paris, France.

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 VSMC’s.

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