Insulin Delivery: An Ever Changing Frontier

Abstract

Insulin transport across vascular endothelial cells is the rate limiting step in its time action profile. Glucose uptake in response to insulin is estimated through different techniques and is influenced by insulin sensitivity of the tissue. Glucose clamp technique and minimal model imply an incremental increase in the levels of insulin in the ISF compartment evidenced by increase in glucose uptake. This can not merely be explanied by tissue capillary recruitment or increase in blood flow of already perfused areas. Although insulin is proven to affect the blood flow and capillary recruitment of already perfused areas, restoration of muscle blood flow in insulin resistant patients does not revert the insulin activity profile. By review of frequently cited articles, it can be interpreted that insulin causes a much greater increase in tissue recruitment by increasing the perfused capillary volume of previously unperfused areas, an increase in the permeability of the capillaries and recruitment of insulin transport receptors. This also results in an Increase in volume of distribution of glucose. Insulin, like other proteins, may be transported across by simple diffusion, paracellular pathway and transcellular pathway with the help of transport receptors. In conclusion, insulin is most likely transported across capillary endothelial cells by more than one mechanism and there may be recruitment of these pathways according to insulin levels. Thus further investigations of these possible pathways may help pave the way for more efficient insulin delivery methods in the future.