Role of the Pancreatic Islet Microvasculature in Health and Disease

The pancreatic islet vasculature comprises microvascular endothelial cells surrounded by mural cells (pericytes). Both cell types support the islet by providing (1) a conduit for delivery and exchange of nutrients and hormones; (2) paracrine signals and extracellular matrix (ECM) components that support islet development, architecture, and endocrine function; and (3) a barrier against inflammation and immune cell infiltration. In type 2 diabetes, the islet vasculature becomes inflamed, showing loss of endothelial cells, detachment, and/or trans-differentiation of pericytes, vessel dilation, and excessive ECM deposition. While most work to date has focused either on endothelial cells or pericytes in isolation, it is very likely that the interaction between these cell types and disruption of that interaction in diabetes are critically important. In fact, dissociation of pericytes from endothelial cells is an early, key feature of microvascular disease in multiple tissues/disease states. Moreover, in beta-cell replacement therapy, co-transplantation with microvessels versus endothelial cells alone is substantially more effective in improving survival and function of the transplanted cells. Ongoing studies, including characterization of islet vascular cell signatures, will aid in the identification of new therapeutic targets aimed at improving islet function and benefiting people living with all forms of diabetes.