The four potential pathways by which insulin may move from the vascular lumen to the interstitium of muscle. The possibility of movement via a paracellular pathway (1) through the junctional structure appears to be unlikely in either the arteriole or capillary bed within skeletal muscle, which has a continuous endothelium. This pathway may be open in small venules, or under circumstances where the endothelium is rendered `leaky'. Insulin could bind to a receptor anywhere on the plasma membrane, leading to internalisation, diffusion to the anti-luminal membrane of the EC and subsequent release into the muscle interstitium (2). Caveolae may allow the passage of insulin as part of a bulk fluid movement in the setting of vesicular trafficking (3). Because of the low plasma concentration of insulin, movement in this manner would be a relatively rare event. Caveolae may also function as areas of insulin receptor localisation. This would facilitate receptor-mediated association of insulin with transporting caveolae and increase the probability of insulin transiting the endothelium as part of a vesicular trafficking process (4)