Antioxidants improve impaired insulin-mediated glucose uptake and prevent migration and proliferation of cultured rabbit coronary smooth muscle cells induced by high glucose

Background-To explore the role of intracellular oxidative stress in high glucose-induced atherogenesis, we examined the effect of probucol and/or alpha-tocopherol on the migration and growth characteristics of-cultured rabbit coronary vascular smooth muscle cells (VSMCs). Methods and Results Chronic high-glucose-medium (22.2 mmol/L) treatment increased platelet-derived growth factor (PDGF)-BB-mediated VSMC migration, [H-3]thymidine incorporation, and cell number compared with VSMCs treated with normal-glucose medium (5.6 mmol/L + 16.6 mmol/L mannose). Probucol and alpha-tocopherol significantly suppressed high glucose-induced increase in VSMC migration, cell number, and [H-3] thymidine incorporation. Probucol and alpha-tocopherol suppressed high glucose-induced elevation of-the cytosolic ratio of NADH/NAD(+), phospholipase D, and membrane-bound protein kinase C activation. Probucol, alpha-tocopherol, and calphostin C improved the high glucose-induced suppression of insulin-mediated [H-3]deoxyglucose uptake. Chronic high-glucose treatment increased the oxidative stress, which was significantly suppressed by probucol, alpha-tocopherol, suramin, and calphostin C. Conclusions-These findings suggest that probucol and alpha-tocopherol may suppress high glucose-induced VSMC migration and proliferation via suppression of increases in the cytosolic ratio of free NADH/NAD(+), phospholipase D, and protein kinase C activation induced by high glucose, which result in reduction in intracellular oxidative stress.