Emerging paracrine functions of the endothelium in the setting of diabetes

The endothelium was originally described and viewed as an inert simple barrier layer lining the vasculature, however, further research exposed the endothelium as an active organ, which contributes not only to normal physiology but also the pathophysiology of several diseases. More recently, evidence is emerging demonstrating that the endothelium can act as a paracrine organ that can dynamically respond to circulating changes depending upon its location and stimuli, including changes in the whole-body metabolic environment. Over the last few decades, changes in human lifestyle have contributed to a pandemic of nutritional obesity, leading to a significant increase in the prevalence of type-2 diabetes mellitus. Therefore, understanding the paracrine actions of the endothelium, especially in the setting of metabolic imbalance, will provide novel therapeutic avenues.