Cell-specific insulin resistance: implications for atherosclerosis.

Insulin resistance is increasingly acknowledged as an independent risk factor for cardiovascular disease. Despite this, our understanding of the cellular and molecular mechanisms that might account for this relationship remain incompletely understood. A key challenge has been in distinguishing between a 'whole-body' milieu of inflammation and oxidative stress from the ramifications of cell-specific resistance to insulin. Transgenic models have now begun to explore the cellular influences of insulin resistance on vascular biology, with novel implications for atherosclerosis across a range of cells including endothelial cells, endothelial progenitor cells, vascular smooth muscle cells, macrophages and fibroblasts. Emerging data from these models have also begun to challenge conventional dogma. In particular, the findings across various cell types are disparate with some even implying a protective influence on vascular biology. We now review these data, highlighting recent advances in our understanding of cellular resistance to insulin as well as those areas where there remains a paucity of data.