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362,363 IR contributes to endothelial dysfunction by decreasing nitric oxide (NO) production via PI3K/Akt pathway from endothelial cells, 364 and increasing reactive oxygen species (ROS) production, prothrombotic factors and proinflammatory markers mediated by MAPK/ERK activity, 365 that both increases the cardiovascular risk, increased ROS levels in turn leads to the inhibition of insulin-PI3K signaling pathway through IRS-1 phosphorylation, which may aggravate IR