The β-cell/EC axis: how do islet cells talk to each other?

Abstract

Within the pancreatic islet, the beta cell represents the ultimate biosensor. Its central function is to accurately sense glucose levels in the blood, and consequently release appropriate amounts of insulin. As the only cell type capable of insulin production, the beta cell must balance this crucial workload with self-preservation and, when required, regeneration. Evidence suggests that the beta cell has an important ally in intra-islet endothelial cells. As well as providing a conduit for delivery of the primary input stimulus (glucose) and dissemination of its most important effector (insulin), intra-islet blood vessels deliver oxygen to these dense clusters of metabolically active cells. Furthermore, it appears that endothelial cells directly impact insulin gene expression, secretion and beta cell survival. This review discusses the molecules and pathways involved in the crosstalk between beta cells and intra-islet endothelial cells. The evidence supporting the intra-islet endothelial cell as an important partner for beta cell function is examined to highlight the relevance of this axis in the context of type 1 and type 2 diabetes. Recent work which has established the potential of endothelial cells or their progenitors to enhance the reestablishment of glycaemic control following pancreatic islet transplantation in animal models is discussed.