Letter by Rask-Madsen et al Regarding Article, “Selective Enhancement of Insulin Sensitivity in the Endothelium In Vivo Reveals a Novel Proatherosclerotic Signaling Loop”
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To the Editor:
In an article published online on December 5, Viswambharan et al1 presents interesting data on atherosclerosis in mice with overexpression of the insulin receptor in vascular endothelial cells. Their work adds to a growing literature on the importance of insulin signaling in endothelial cells with impact on blood flow regulation, whole-body metabolism, angiogenesis, and atherogenesis. Viswambharan et al ascribe increased atherosclerosis in these mice to overactive signaling through Akt, an important pathway activated by insulin. However, it is important to note that gain of insulin-stimulated Akt signaling in endothelial cells may not model any common human condition.
In many tissues, insulin-stimulated phosphatidylinositol 3-kinase/Akt signaling is impaired, whereas other signaling pathways through MAPK (mitogen-activated protein kinase)2 or SREBP-1c (sterol regulatory element binding protein-1c)3 remain sensitive to insulin. To describe this phenomenon, we proposed the term selective insulin resistance in 1999.2 This concept has been embraced by many groups working on insulin signaling in endothelial cells and other cell types.4–7 According to this concept, insulin-stimulated Akt activation is impaired in endothelial cells in obesity or diabetes mellitus. Hyperinsulinemia develops as compensatory …