The Endothelial Barrier is not Rate-limiting to Insulin Action in the Myocardium

Diabetes is characterized by the impaired function of the pancreatic hormone insulin. The exit of insulin from the capillaries requires its passage across endothelial cells. Whether the endothelium acts as a rate-limiting barrier to insulin transport is controversial.We hypothesized that if the endothelial barrier is rate-limiting to insulin transport, then increasing endothelial permeability will accelerate insulin action on downstream tissues. To address the question, we developed a murine ex vivo aortic perfusion model which delivers insulin to the heart. We demonstrated that despite conditions that significantly increased cardiac vascular permeability, insulin action was not accelerated. These data indicate that the endothelial barrier is not rate-limiting to insulin action in the myocardium. Efforts to decrease insulin resistance should focus on downstream tissues or regulation of blood flow rather than the transendothelial transport of insulin.M.Sc