Garlic extract methylallyl thiosulfinate blocks insulin potentiation of platelet-derived growth factor-stimulated migration of vascular smooth muscle cells.

Platelet-derived growth factor (PDGF) is a potent inducer of vascular smooth muscle cell (VSMC) migration, whereas insulin, in physiological concentrations, helps maintain the nonproliferative phenotype of these cells. However, hyperinsulinemia (10 nmol/L) significantly potentiates the PDGF (30 pmol/L)-induced migration of VSMC. This potentiating effect of hyperinsulinemia appears to be mediated by increased availability of geranylgeranylated Rho-A.

Inhibition of phosphatidylinositol 3-kinase enhances mitogenic actions of insulin in endothelial cells.

The concept of "selective insulin resistance" has emerged as a unifying hypothesis in attempts to reconcile the influence of insulin resistance with that of hyperinsulinemia in the pathogenesis of macrovascular complications of diabetes. To explore this hypothesis in endothelial cells, we designed a set of experiments to mimic the "typical metabolic insulin resistance" by blocking the phosphatidylinositol 3-kinase pathway and exposing the cells to increasing concentrations of insulin ("compensatory hyperinsulinemia"). Inhibition of phosphatidylinositol 3-kinase with wortmannin blocked the ability of insulin to stimulate increased expression of endothelial nitric-oxide synthase, did not affect insulin-induced activation of MAP kinase, and increased the effects of insulin on prenylation of Ras and Rho proteins.