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In order for insulin to exert its biological actions on target cells in peripheral tissues like muscle and adipose tissues, Insulin must pass through the endothelial barrier into the interstitium.Insulin’s trans-endothelial transport (TET), particularly in muscle where capillaries are lined by a continuous endothelium, determines tissue insulin levels, and thereby critically determines insulin’s metabolic effects [1-6]. This process is significantly impaired in insulin resistance states such as obesity and type 2 diabetes [2,7-9]. Current evidence obtained by us and others indicate that insulin TET is transcellular process and mediated by transporting caveolae that contain or associate with multiple structural and signaling molecules including the insulin receptor (IR), IGF-1receptor, caveolin-1, dynamin-2, actin filaments and eNOS